MicroRNAs: Novel players in the diagnosis and treatment of cancer cachexia (Review)
- Authors:
- Published online on: May 16, 2022 https://doi.org/10.3892/etm.2022.11373
- Article Number: 446
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Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
Abstract
1. Introduction
Cachexia is a complex syndrome featuring loss of weight that results from reduced skeletal muscle mass (1). This syndrome usually appears in the late stages of severe illnesses, including cancer, kidney disease, human immunodeficiency virus, congestive heart failure and chronic obstructive pulmonary disease (2,3). Patients with cachexia are insensitive to treatment, have a low quality of life and have a high mortality rate (4).
Cancer cachexia affects 50% of patients with cancer and causes ~40% of cancer-associated mortalities (5). The incidence of cancer cachexia changes with the stage and type of cancer (6). According to a previous cohort study on patients with advanced tumors, those with pancreatic cancer are at the greatest risk of developing cancer cachexia (~70%), followed by colorectal, gastroesophageal, and head and neck cancer (~45%) (7), while patients with breast and prostate cancer are at the lowest risk of developing cachexia (20-30%) (7). In addition, cancer cachexia may result in inefficient chemotherapy, increased treatment interruptions or decreased survival rates (8).
The diagnostic standard of cachexia is loss of weight >5% or >2% among patients who have a body mass index (BMI) less than 20 kg/m2 (9). In addition, neuroendocrine changes occur in patients with cancer cachexia, leading to early satiety and food aversion (10). The Warburg effect is the catabolism of glucose to lactate to obtain adenosine triphosphate (11). Lactate is converted to glucose in the liver at a cost of energy. When glucose is released into the bloodstream, cancer cells may use it again for glycolysis. The Cori cycle is a fruitless glucose-lactate shuttle that increases energy expenditure and hepatic gluconeogenesis (12). As a result, catabolic metabolism in fat and skeletal muscle provides additional glucose precursors for gluconeogenesis. In cachexia, the Warburg effect in myocytes contributes to muscle mass reduction (13). Reduced food absorption and excessive metabolism eventually lead to a negative energy balance and mass loss, particularly skeletal muscle mass loss (5). Decreased skeletal muscle mass and muscle function are found to negatively influence the life quality among patients with cancer cachexia and have recently been widely referred to as ‘sarcopenia’ (14,15). Cancer cachexia may subsequently progress to refractory cachexia, and interventions at such stage are unlikely to be successful.
Currently, there are limited options for the treatment of cancer cachexia. There are two therapeutic concepts: i) non-pharmacological options, which are focused on nutrition and exercise interventions (3,16); and ii) chemotherapy, including the usage of hormone therapy (e.g. gonadotropins), myostatin inhibitors and anti-inflammatory drugs (17). However, the effectiveness of these treatments remains unclear, as clinical outcomes and long-term efficacy reports are insufficient (18). Therefore, novel early diagnostic biomarkers and therapeutic targets for cancer cachexia are needed (19).
Several microRNAs (miRNAs or miRs), such as let-7d-3p and miR-345-5p, were found to be markedly dysregulated among patients with cachexia (6,20). Furthermore, several miRNAs have been found to have a regulatory effect on inflammatory pathways, and on the degradation and synthesis of proteins in skeletal muscle, which makes miRNAs potential novel therapeutic candidates in cancer cachexia therapy (21,22). The present review summarizes miRNAs differentially expressed in specimens derived from patients with cancer cachexia, including muscle, adipose tissue and blood. In addition, the present review proposes that miRNAs may be considered as potential diagnostic markers or therapeutic targets for cancer cachexia.
2. miRNAs in the development of cancer and cancer cachexia
miRNAs are short RNAs that can regulate the expression of ~60% of protein-encoding genes of human mRNAs (23). miRNAs were firstly identified in 1993, and additional types of miRNAs have been identified and studied since then (24). The miRBase database contains published miRNA sequences, and the up-to-date version of this database contains >2,570 mature miRNAs from humans (25). The majority of miRNAs can be transcribed by RNA polymerase (pol) II or pol III in the nucleus to produce primary precursor miRNAs (pri-miRNAs) (60-100 nt) (Fig. 1) (26). The Drosha/DiGeorge critical region 8 ribonuclease complex divides pri-miRNAs to generate precursor pre-miRNAs, which are later exported to the cytoplasm via the exportin-5 complex (27). The Dicer/TAR-RNA binding protein complex subsequently divides pre-miRNAs to produce mature double-stranded miRNAs (28). To become functional, double-stranded miRNAs are then disassembled to produce passenger and guide strands. The passenger strand is degraded, while the guide strand is loaded onto the RNA-induced silencing complex (29,30). The primary function of miRNAs is to inhibit the translation of target mRNAs.
miRNA expression profiling shows that changes in miRNA expression are associated with various illnesses, including primary muscle diseases, dexamethasone-induced atrophy, diabetes and wasting diseases (such as cancer cachexia) (31,32). In addition, various aspects of metabolic changes and inflammatory responses are also regulated by miRNAs (33-35). Hypermetabolism and systemic inflammation are typical symptoms of cancer cachexia (36). Therefore, miRNAs possibly impact cancer cachexia pathogenesis.
Cancer cells may produce inflammatory cytokines and cause local and systemic inflammation in the host (37,38). Previous studies have demonstrated that the tumor itself may be capable of secreting exosomes containing miRNAs (39-42), which can increase the synthesis of circulating inflammatory factors (39). The levels of circulating inflammatory cytokines, including tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), interleukin 1 (IL-1) and IL-6, can be also altered in patients with cachexia (43,44). miRNAs can be transported via exosomes, which can be secreted into the serum, cerebrospinal fluid, urine and saliva (45). Exosomes from adipose tissue in the tumor microenvironment may also promote the development of systemic inflammation (46,47).
miR-182-5p, miR-183-5p, miR-21-5p, the miR-200 family, miR-7-5p, miR-125b-5p, miR-96-5p, miR-139-5p, miR-99a-5p, miR-497-5p and miR-486-5p have been found to be altered in breast cancer (BC) (48). A total of 26 differentially expressed miRNAs were found to interact with frequently deregulated genes known to be involved in colorectal cancer pathways (49). The majority of these miRNAs could predict the prognosis of patients with colorectal cancer in stages II and III (49). It has been demonstrated that miRNAs can be used for the early detection of oral cancer (50). A total of 9 differentially expressed miRNAs (miR-486-1, miR-486-2, miR-153, miR-210, miR-9-1, miR-9-2, miR-9-3, miR-577 and miR-4732) have been identified, which could be used as lung adenocarcinoma diagnostic biomarkers (51).
In addition, miRNAs may have a prognostic value for patients treated with a combination of interventions, including diet and physical activity (48). Differentially expressed extracellular vesicle (EV) miRNAs resulting from the Mediterranean diet may be engaged in pathways associated with cardiometabolic risk factors in overweight BC survivors (52). In addition, environmental factors such as pesticides may modify miRNA expression and the DNA methylation status (53). Alteration of miRNA expression profiles upon exposure to naturally occurring asbestiform fibers is a diagnostic indicator of mesothelial neoplastic transformation (54). In patients with colon cancer, vascular endothelial growth factor (VEGF) may be an independent predictor of weight loss (55). VEGF promotes the proliferation, migration and tube formation of endothelial cells (ECs), and has become a primary target of anti-angiogenic therapy (56-59). Furthermore, VEGF is linked to systemic inflammation and malnutrition, supporting the possible involvement of VEGF in cancer cachexia pathogenesis (55). VEGF is required for tumor angiogenesis, and inhibition of VEGF inhibits angiogenesis and tumor growth (57,60-62). miRNAs promote angiogenesis by facilitating the proliferation and migration of ECs (63). The hypoxia inducible factor-1α/VEGF signaling pathways regulated by miR-210, miR-21 and miR-126 play a role in colon cancer initiation (64). Overexpression of miR-638 could inhibit angiogenesis and tumor growth in hepatocellular carcinoma by suppressing VEGF signaling (65). miRNAs produced from tumor cells, such as miR-23a, miR-494 and miR-210, were reported to be packaged into EVs and transported to recipient ECs (66). These miRNAs promote angiogenesis by facilitating the proliferation and migration of ECs (63).
3. miRNAs in muscular atrophy
Patients with cancer cachexia can lose ≤75% of their skeletal muscle mass, which may lead to poor prognosis and higher mortality associated with cancer (67). Muscle protein degradation in cancer cachexia is mediated mainly by the ubiquitin proteasome system, induced by activation of E3 ligands (68). The Fork head box O (FoxO) signaling pathway is involved in this process by inducing the transcription of E3 ubiquitin ligases, of which there are three members in skeletal muscle: FoxO3, FoxO1 and FoxO4(68). Inhibition of FoxO transcriptional activity attenuates muscle fiber atrophy during cachexia (69). miRNA-486 reduces FoxO1 protein expression and enhances FoxO1 phosphorylation to inhibit E3 ubiquitin ligase (70). miR-21 associates with and activates Toll-like receptor 7, which induces apoptosis in muscle cells via the c-Jun N-terminal kinase pathway, leading to atrophy (18).
Dysregulated expression of miRNAs (such as myomiRNAs, a subset of miRNAs with high expression in skeletal muscle) is associated with muscle atrophy, which is a hallmark of cancer cachexia (71-74). The expression profile of miRNAs in rectus abdominis muscle samples was evaluated among patients with cancer who exhibited or not a cachexia syndrome (6). In that study, 8 miRNAs were upregulated among patients with cancer cachexia, including let-7d-3p, miR-423-5p, miR-345-5p, miR-532-5p, miR-3184-3p, miR-1296-5p, miR-423-3p and miR-199a-3p (6). Pathway analysis indicated that the target miRNAs were enriched in the adipogenesis, myogenesis, inflammation and innate immune response pathways (6). In another study, the expression levels of 754 miRNAs in broad fascia biopsies of 8 healthy individuals and 8 patients with non-small cell lung cancer who exhibited cachexia were investigated (75). The expression of 28 miRNAs was significantly changed, with 23 miRNAs being downregulated and 5 upregulated (75). In addition, the genes of TNF, transforming growth factor-β, IL-6 and insulin are among the 158 putative target genes identified using miRTarBase (75). A total of 9 miRNAs were found to be differentially expressed in muscles of a cancer cachexia mouse model (20). miRNA-mRNA co-sequencing revealed activation of the atrophy-related transcription factors STAT3, NF-κB and FoxO, thus exposing transcriptional and post-transcriptional regulatory networks involved in muscle wasting (76).
4. miRNAs in adipose tissue depletion
The hallmarks of cancer cachexia are muscle loss, browning of white adipose tissue (WAT) and lipolysis (77,78). Increased levels of circulating inflammatory cytokines can also induce lipolysis and proteolysis in adipose tissue and muscle, respectively, as well as downregulate protein synthesis, which causes a reduction in skeletal muscle mass and adipose tissue in patients with cancer cachexia (21). WAT can promote the circulation of inflammatory cytokines as well as regulate inflammatory processes in immune cells and tissues by secreting miRNA-containing exosomes (79-81). miR-483-5p, miR-744, miR-23a and miR-99b were found to be downregulated in the abdomen subcutaneous adipose tissue of patients with gastrointestinal cancer and cachexia in contrast to those of patients without cachexia syndrome, while the expression of miR-378 was upregulated (82). miRNAs in blood may serve as non-invasive biomarkers of cancer malignancy, and miRNAs can remain highly stable in blood.
5. Circulating miRNAs in cancer cachexia
miRNAs also present in serum, saliva, plasma, urine, and cerebrospinal fluid (83,84). The psoas muscle mass index (PMI) provides a simple approach to describing skeletal muscle volume in the body (85,86). A study on miR-203 in the blood of patients with colorectal cancer demonstrated that patients with low PMI had higher levels of miR-203 than those with high PMI (87). Furthermore, overexpression of miR-203 in serum is an independent predictor of sarcopenia (87). Similarly, previous studies have shown that the level of miR-21 increased in the blood of patients with colorectal cancer who developed cancer cachexia compared with that of patients who did not develop cancer cachexia (88).
Exosomes are the most common type of EVs, which are small membrane-bound vesicles between 30 and 150 nm in diameter (89). The presence of miRNA-rich circulating exosomes may promote the development and maintenance of systemic chronic inflammation in patients with cancer cachexia (21,89). Furthermore, a previous study reported the upregulation of miR-155 in exosomes of BC cells (4T1), which can target peroxisome proliferator-activated receptor-γ in adipocytes, and promote adipocyte metabolism and browning differentiation (90). In conclusion, tumor-derived exosomal miRNAs may induce cancer cachexia, and therefore exosomal miRNAs are considered potential early diagnostic markers of cancer cachexia (90-94).
6. Discussion and perspectives
Dysregulation of specific miRNAs, such as let-7d-3p, miR-345-5p, miR-532-5p, miR-378, miR-92a-3p, miR-21, is involved in the development of cachexia. Cachexia may induce the differential expression of miRNAs but it has not been validated. Dysregulated expression of miRNAs was observed in muscle tissue, adipose tissue and blood specimens from patients with cancer cachexia in contrast to the findings in patients who did not exhibit cancer cachexia or in healthy controls (Table I) (6,75,82,87,88,95-97). However, miRNAs directly obtained from adipose or muscle tissue biopsies are not applicable as diagnostic markers of cancer cachexia (84). Thus, the diagnostic value of miRNAs for cancer cachexia should be restricted to circulating miRNAs. miRNAs with high stability in body fluids can be potentially used as non-invasive markers (98,99). miRNAs from plasma/serum have been reported as biomarkers for the early diagnosis of different types of tumor, including gastric cancer (100), BC (101) and pancreatic cancer (102). Therefore, it can be proposed that circulating miRNAs in the blood can be used as biomarkers to differentiate patients at risk of developing cancer cachexia. For example, circulating miRNAs such as miR-21 may serve as markers for diagnosing cancer cachexia among patients likely to develop colorectal cancer (88). However, the application of using circulating miRNAs in patients with cancer as biomarkers for diagnosis needs to be validated in future clinical trials.
Multiple characteristics of miRNAs make them potential targets for new treatments of cancer cachexia. Firstly, miRNAs regulate the translation of mRNAs belonging to multiple genes and signaling pathways that are dysregulated in cancer cachexia, such as TNF, IFN signaling, STAT and NF-κB transcription factors and associated target genes (15,103-105). Secondly, miRNAs have been used to promote muscle development and maintain muscle homeostasis (106). The expression of multiple miRNAs has been found to be dysregulated in muscle wasting of cachexia (107). Thirdly, treatment of cancer cachexia with miRNAs can induce reversible and specific changes in gene regulation without affecting the DNA (108). miRNAs can be used as knockdown complementary mRNA targets (103). In knockdown therapy, complement-specific miRNA drugs compete with their mRNA targets for translation. Fourthly, EVs can prevent miRNAs from being degraded in transfer and expedite their uptake via target cells (109,110). Finally, miRNAs can be efficiently stabilized or concentrated using novel processing methods (103,111). However, no miRNA drugs have been clinically used to date, although there are several ongoing clinical trials on phases 1 and 2(112). For example, a phase I clinical study that applied miR-16 mimics for the treatment of non-small cell lung cancer or mesothelioma was accomplished, and may be followed up by a phase II study (113). miRNAs have also been adopted for targeting serum amyloid 1 and 2, which are lipoproteins usually generated in response to inflammatory cytokines, and were shown to successfully relieve muscle atrophy in a pre-clinical mouse model (114). miRNA mimics already used in clinical studies for cancer therapy, such as miR-16, can be investigated in animal models of cancer cachexia to evaluate whether they can improve weight loss and alleviate cancer cachexia symptoms. The implications of miRNAs in the pathogenesis of cancer cachexia make them attractive therapeutic targets. In addition, miRNA-based therapies for cancer cachexia target specific pathways that have the potential to restore homeostasis in chronically dysfunctional networks and enable positive muscle responses to exercise and diet.
Acknowledgements
Not applicable.
Funding
Funding: This study is supported by Shandong Provincial Administration of Traditional Chinese Medicine (grant no. 2017 218) and Department of Science and Technology of Shandong Province (2019GSF108234).
Availability of data and materials
Not applicable.
Authors' contributions
ZL conceived and designed the review. XL, LD and QL wrote the first draft of the manuscript in light of the literature data. Data authentication is not applicable. All authors contributed to the article and approved the submitted version for publication.
Ethics approval and consent to participate
Not applicable.
Patient consent for publication
Not applicable.
Competing interests
The authors declare that they have no competing interests.
References
|
Evans WJ, Morley JE, Argilés J, Bales C, Baracos V, Guttridge D, Jatoi A, Kalantar-Zadeh K, Lochs H, Mantovani G, et al: Cachexia: A new definition. Clin Nutr. 27:793–799. 2008.PubMed/NCBI View Article : Google Scholar | |
|
Holecek M: Muscle wasting in animal models of severe illness. Int J Exp Pathol. 93:157–171. 2012.PubMed/NCBI View Article : Google Scholar | |
|
Argilés JM, Busquets S, Stemmler B and López-Soriano FJ: Cancer cachexia: Understanding the molecular basis. Nat Rev Cancer. 14:754–762. 2014.PubMed/NCBI View Article : Google Scholar | |
|
Nixon DW, Heymsfield SB, Cohen AE, Kutner MH, Ansley J, Lawson DH and Rudman D: Protein-calorie undernutrition in hospitalized cancer patients. Am J Med. 68:683–690. 1980.PubMed/NCBI View Article : Google Scholar | |
|
Fearon KC, Glass DJ and Guttridge DC: Cancer cachexia: Mediators, signaling, and metabolic pathways. Cell Metab. 16:153–166. 2012.PubMed/NCBI View Article : Google Scholar | |
|
Narasimhan A, Ghosh S, Stretch C, Greiner R, Bathe OF, Baracos V and Damaraju S: Small RNAome profiling from human skeletal muscle: Novel miRNAs and their targets associated with cancer cachexia. J Cachexia Sarcopenia Muscle. 8:405–416. 2017.PubMed/NCBI View Article : Google Scholar | |
|
Anker MS, Holcomb R, Muscaritoli M, von Haehling S, Haverkamp W, Jatoi A, Morley JE, Strasser F, Landmesser U, Coats AJS and Anker SD: Orphan disease status of cancer cachexia in the USA and in the European Union: A systematic review. J Cachexia Sarcopenia Muscle. 10:22–34. 2019.PubMed/NCBI View Article : Google Scholar | |
|
Caillet P, Liuu E, Raynaud Simon A, Bonnefoy M, Guerin O, Berrut G, Lesourd B, Jeandel C, Ferry M, Rolland Y and Paillaud E: Association between cachexia, chemotherapy and outcomes in older cancer patients: A systematic review. Clin Nutr. 36:1473–1482. 2017.PubMed/NCBI View Article : Google Scholar | |
|
Fearon K, Strasser F, Anker SD, Bosaeus I, Bruera E, Fainsinger RL, Jatoi A, Loprinzi C, MacDonald N, Mantovani G, et al: Definition and classification of cancer cachexia: An international consensus. Lancet Oncol. 12:489–495. 2011.PubMed/NCBI View Article : Google Scholar | |
|
Thoresen L, Frykholm G, Lydersen S, Ulveland H, Baracos V, Prado CM, Birdsell L and Falkmer U: Nutritional status, cachexia and survival in patients with advanced colorectal carcinoma. Different assessment criteria for nutritional status provide unequal results. Clin Nutr. 32:65–72. 2013.PubMed/NCBI View Article : Google Scholar | |
|
Vander Heiden MG, Cantley LC and Thompson CB: Understanding the Warburg effect: The metabolic requirements of cell proliferation. Science. 324:1029–1033. 2009.PubMed/NCBI View Article : Google Scholar | |
|
Phypers B and Pierce JT: Lactate physiology in health and disease. CEACCP. 6:128–132. 2001. | |
|
Der-Torossian H, Gourin CG and Couch ME: Translational implications of novel findings in cancer cachexia: The use of metabolomics and the potential of cardiac malfunction. Curr Opin Support Palliat Care. 6:446–450. 2012.PubMed/NCBI View Article : Google Scholar | |
|
Muscaritoli M, Anker SD, Argilés J, Aversa Z, Bauer JM, Biolo G, Boirie Y, Bosaeus I, Cederholm T, Costelli P, et al: Consensus definition of sarcopenia, cachexia and pre-cachexia: Joint document elaborated by Special Interest Groups (SIG) ‘cachexia-anorexia in chronic wasting diseases’ and ‘nutrition in geriatrics’. Clin Nutr. 29:154–159. 2010.PubMed/NCBI View Article : Google Scholar | |
|
Freire PP, Fernandez GJ, Cury SS, de Moraes D, Oliveira JS, de Oliveira G, Dal-Pai-Silva M, Dos Reis PP and Carvalho RF: The pathway to cancer cachexia: MicroRNA-Regulated networks in muscle wasting based on integrative meta-analysis. Int J Mol Sci. 20(1962)2019.PubMed/NCBI View Article : Google Scholar | |
|
Schmidt SF, Rohm M, Herzig S and Berriel Diaz M: Cancer cachexia: More than skeletal muscle wasting. Trends Cancer. 4:849–860. 2018.PubMed/NCBI View Article : Google Scholar | |
|
Argilés JM, Anguera A and Stemmler B: A new look at an old drug for the treatment of cancer cachexia: Megestrol acetate. Clin Nutr. 32:319–324. 2013.PubMed/NCBI View Article : Google Scholar | |
|
He WA, Calore F, Londhe P, Canella A, Guttridge DC and Croce CM: Microvesicles containing miRNAs promote muscle cell death in cancer cachexia via TLR7. Proc Natl Acad Sci USA. 111:4525–4529. 2014.PubMed/NCBI View Article : Google Scholar | |
|
Wang YW, Ma X, Zhang YA, Wang MJ, Yatabe Y, Lam S, Girard L, Chen JY and Gazdar AF: ITPKA gene body methylation regulates gene expression and serves as an early diagnostic marker in lung and other cancers. J Thorac Oncol. 11:1469–1481. 2016.PubMed/NCBI View Article : Google Scholar | |
|
Lee DE, Brown JL, Rosa-Caldwell ME, Blackwell TA, Perry RA Jr, Brown LA, Khatri B, Seo D, Bottje WG, Washington TA, et al: Cancer cachexia-induced muscle atrophy: Evidence for alterations in microRNAs important for muscle size. Physiol Genomics. 49:253–260. 2017.PubMed/NCBI View Article : Google Scholar | |
|
Camargo RG, Quintas Teixeira Ribeiro H, Geraldo MV, Matos-Neto E, Neves RX, Carnevali LC Jr, Donatto FF, Alcântara PS, Ottoch JP and Seelaender M: Cancer cachexia and MicroRNAs. Mediators Inflamm. 2015(367561)2015.PubMed/NCBI View Article : Google Scholar | |
|
Li X, Wang S, Zhu R, Li H, Han Q and Zhao RC: Lung tumor exosomes induce a pro-inflammatory phenotype in mesenchymal stem cells via NFκB-TLR signaling pathway. J Hematol Oncol. 9(42)2016.PubMed/NCBI View Article : Google Scholar | |
|
Ha M and Kim VN: Regulation of microRNA biogenesis. Nat Rev Mol Cell Biol. 15:509–524. 2014.PubMed/NCBI View Article : Google Scholar | |
|
Lee RC, Feinbaum RL and Ambros V: The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell. 75:843–854. 1993.PubMed/NCBI View Article : Google Scholar | |
|
Stegeman S, Amankwah E, Klein K, O'Mara TA, Kim D, Lin HY, Permuth-Wey J, Sellers TA, Srinivasan S, Eeles R, et al: A Large-scale analysis of genetic variants within putative miRNA binding sites in prostate cancer. Cancer Discov. 5:368–379. 2015.PubMed/NCBI View Article : Google Scholar | |
|
Lee Y, Kim M, Han J, Yeom KH, Lee S, Baek SH and Kim VN: MicroRNA genes are transcribed by RNA polymerase II. EMBO J. 23:4051–4060. 2004.PubMed/NCBI View Article : Google Scholar | |
|
Denli AM, Tops BB, Plasterk RH, Ketting RF and Hannon GJ: Processing of primary microRNAs by the Microprocessor complex. Nature. 432:231–235. 2004.PubMed/NCBI View Article : Google Scholar | |
|
Wilson RC, Tambe A, Kidwell MA, Noland CL, Schneider CP and Doudna JA: Dicer-TRBP complex formation ensures accurate mammalian microRNA biogenesis. Mol Cell. 57:397–407. 2015.PubMed/NCBI View Article : Google Scholar | |
|
Gregory RI, Chendrimada TP, Cooch N and Shiekhattar R: Human RISC couples microRNA biogenesis and posttranscriptional gene silencing. Cell. 123:631–640. 2005.PubMed/NCBI View Article : Google Scholar | |
|
Thomson DW, Bracken CP and Goodall GJ: Experimental strategies for microRNA target identification. Nucleic Acids Res. 39:6845–6853. 2011.PubMed/NCBI View Article : Google Scholar | |
|
Eisenberg I, Eran A, Nishino I, Moggio M, Lamperti C, Amato AA, Lidov HG, Kang PB, North KN, Mitrani-Rosenbaum S, et al: Distinctive patterns of microRNA expression in primary muscular disorders. Proc Natl Acad Sci USA. 104:17016–17021. 2007.PubMed/NCBI View Article : Google Scholar | |
|
Soares RJ, Cagnin S, Chemello F, Silvestrin M, Musaro A, De Pitta C, Lanfranchi G and Sandri M: Involvement of microRNAs in the regulation of muscle wasting during catabolic conditions. J Biol Chem. 289:21909–21925. 2014.PubMed/NCBI View Article : Google Scholar | |
|
Poy MN, Eliasson L, Krutzfeldt J, Kuwajima S, Ma X, Macdonald PE, Pfeffer S, Tuschl T, Rajewsky N, Rorsman P and Stoffel M: A pancreatic islet-specific microRNA regulates insulin secretion. Nature. 432:226–230. 2004.PubMed/NCBI View Article : Google Scholar | |
|
Zhou X, Hu S, Zhang Y, Du G and Li Y: The mechanism by which noncoding RNAs regulate muscle wasting in cancer cachexia. Precision Clin Med. 4:136–147. 2021. | |
|
Marceca GP, Nigita G, Calore F and Croce CM: MicroRNAs in skeletal muscle and hints on their potential role in muscle wasting during cancer cachexia. Front Oncol. 10(607196)2020.PubMed/NCBI View Article : Google Scholar | |
|
Kim DH: Nutritional issues in patients with cancer. Intest Res. 17:455–462. 2019.PubMed/NCBI View Article : Google Scholar | |
|
Zhu X, Burfeind KG, Michaelis KA, Braun TP, Olson B, Pelz KR, Morgan TK and Marks DL: MyD88 signalling is critical in the development of pancreatic cancer cachexia. J Cachexia Sarcopenia Muscle. 10:378–390. 2019.PubMed/NCBI View Article : Google Scholar | |
|
Du L, Dong F, Guo L, Hou Y, Yi F, Liu J and Xu D: Interleukin-1β increases permeability and upregulates the expression of vascular endothelial-cadherin in human renal glomerular endothelial cells. Mol Med Rep. 11:3708–3714. 2015.PubMed/NCBI View Article : Google Scholar | |
|
Lobb RJ, Lima LG and Möller A: Exosomes: Key mediators of metastasis and pre-metastatic niche formation. Semin Cell Dev Biol. 67:3–10. 2017.PubMed/NCBI View Article : Google Scholar | |
|
Tomasetti M, Lee W, Santarelli L and Neuzil J: Exosome-derived microRNAs in cancer metabolism: Possible implications in cancer diagnostics and therapy. Exp Mol Med. 49(e285)2017.PubMed/NCBI View Article : Google Scholar | |
|
Cordonnier M, Chanteloup G, Isambert N, Seigneuric R, Fumoleau P, Garrido C and Gobbo J: Exosomes in cancer theranostic: Diamonds in the rough. Cell Adh Migr. 11:151–163. 2017.PubMed/NCBI View Article : Google Scholar | |
|
Song W, Yan D, Wei T, Liu Q, Zhou X and Liu J: Tumor-derived extracellular vesicles in angiogenesis. Biomed Pharmacother. 102:1203–1208. 2018.PubMed/NCBI View Article : Google Scholar | |
|
Bilir C, Engin H, Can M, Temi YB and Demirtas D: The prognostic role of inflammation and hormones in patients with metastatic cancer with cachexia. Med Oncol. 32(56)2015.PubMed/NCBI View Article : Google Scholar | |
|
Batista ML Jr, Olivan M, Alcantara PS, Sandoval R, Peres SB, Neves RX, Silverio R, Maximiano LF, Otoch JP and Seelaender M: Adipose tissue-derived factors as potential biomarkers in cachectic cancer patients. Cytokine. 61:532–539. 2013.PubMed/NCBI View Article : Google Scholar | |
|
Nie M, Deng ZL, Liu J and Wang DZ: Noncoding RNAs, emerging regulators of skeletal muscle development and diseases. Biomed Res Int. 2015(676575)2015.PubMed/NCBI View Article : Google Scholar | |
|
Zhang Y, Yu M and Tian W: Physiological and pathological impact of exosomes of adipose tissue. Cell Prolif. 49:3–13. 2016.PubMed/NCBI View Article : Google Scholar | |
|
Lazar I, Clement E, Dauvillier S, Milhas D, Ducoux-Petit M, LeGonidec S, Moro C, Soldan V, Dalle S, Balor S, et al: Adipocyte exosomes promote melanoma aggressiveness through fatty acid oxidation: A novel mechanism linking obesity and cancer. Cancer Res. 76:4051–4057. 2016.PubMed/NCBI View Article : Google Scholar | |
|
Falzone L, Grimaldi M, Celentano E, Augustin LSA and Libra M: Identification of modulated MicroRNAs associated with breast cancer, diet, and physical activity. Cancers (Basel). 12(2555)2020.PubMed/NCBI View Article : Google Scholar | |
|
Fonseca A, Ramalhete SV, Mestre A, Pires das Neves R, Marreiros A, Castelo-Branco P and Roberto VP: Identification of colorectal cancer associated biomarkers: An integrated analysis of miRNA expression. Aging (Albany NY). 13:21991–22029. 2021.PubMed/NCBI View Article : Google Scholar | |
|
Falzone L, Lupo G, La Rosa GRM, Crimi S, Anfuso CD, Salemi R, Rapisarda E, Libra M and Candido S: Identification of novel MicroRNAs and their diagnostic and prognostic significance in oral cancer. Cancers (Basel). 11(610)2019.PubMed/NCBI View Article : Google Scholar | |
|
Ren ZP, Hou XB, Tian XD, Guo JT, Zhang LB, Xue ZQ, Deng JQ, Zhang SW, Pan JY and Chu XY: Identification of nine microRNAs as potential biomarkers for lung adenocarcinoma. FEBS Open Bio. 9:315–327. 2019.PubMed/NCBI View Article : Google Scholar | |
|
Kwon YJ, Cho YE, Cho AR, Choi WJ, Yun S, Park H, Kim HS, Cashion AK, Gill J, Lee H and Lee JW: The possible influence of mediterranean diet on extracellular vesicle miRNA expression in breast cancer survivors. Cancers (Basel). 12(1355)2020.PubMed/NCBI View Article : Google Scholar | |
|
Giambò F, Leone GM, Gattuso G, Rizzo R, Cosentino A, Cinà D, Teodoro M, Costa C, Tsatsakis A, Fenga C and Falzone L: Genetic and epigenetic alterations induced by pesticide exposure: Integrated analysis of gene expression, microRNA Expression, and DNA methylation datasets. Int J Environ Res Public Health. 18(8697)2021.PubMed/NCBI View Article : Google Scholar | |
|
Filetti V, Falzone L, Rapisarda V, Caltabiano R, Eleonora Graziano AC, Ledda C and Loreto C: Modulation of microRNA expression levels after naturally occurring asbestiform fibers exposure as a diagnostic biomarker of mesothelial neoplastic transformation. Ecotoxicol Environ Saf. 198(110640)2020.PubMed/NCBI View Article : Google Scholar | |
|
Kemik O, Sumer A, Kemik AS, Hasirci I, Purisa S, Dulger AC, Demiriz B and Tuzun S: The relationship among acute-phase response proteins, cytokines and hormones in cachectic patients with colon cancer. World J Surg Oncol. 8(85)2010.PubMed/NCBI View Article : Google Scholar | |
|
Guo L, Dong F, Hou Y, Cai W, Zhou X, Huang AL, Yang M, Allen TD and Liu J: Dihydroartemisinin inhibits vascular endothelial growth factor-induced endothelial cell migration by a p38 mitogen-activated protein kinase-independent pathway. Exp Ther Med. 8:1707–1712. 2014.PubMed/NCBI View Article : Google Scholar | |
|
Wei T, Jia J, Wada Y, Kapron CM and Liu J: Dose dependent effects of cadmium on tumor angiogenesis. Oncotarget. 8:44944–44959. 2017.PubMed/NCBI View Article : Google Scholar | |
|
Gao P, Wang LL, Liu J, Dong F, Song W, Liao L, Wang B, Zhang W, Zhou X, Xie Q, et al: Dihydroartemisinin inhibits endothelial cell tube formation by suppression of the STAT3 signaling pathway. Life Sci. 242(117221)2020.PubMed/NCBI View Article : Google Scholar | |
|
Liu J, Ren Y, Hou Y, Zhang C, Wang B, Li X, Sun R and Liu J: Dihydroartemisinin induces endothelial cell autophagy through suppression of the Akt/mTOR Pathway. J Cancer. 10:6057–6064. 2019.PubMed/NCBI View Article : Google Scholar | |
|
Xie Q, Cheng Z, Chen X, Lobe CG and Liu J: The role of Notch signalling in ovarian angiogenesis. J Ovarian Res. 10(13)2017.PubMed/NCBI View Article : Google Scholar | |
|
Kim KJ, Li B, Winer J, Armanini M, Gillett N, Phillips HS and Ferrara N: Inhibition of vascular endothelial growth factor-induced angiogenesis suppresses tumour growth in vivo. Nature. 362:841–844. 1993.PubMed/NCBI View Article : Google Scholar | |
|
Liu J, Li Y, Dong F, Li L, Masuda T, Allen TD and Lobe CG: Trichostatin A suppresses lung adenocarcinoma development in Grg1 overexpressing transgenic mice. Biochem Biophys Res Commun. 463:1230–1236. 2015.PubMed/NCBI View Article : Google Scholar | |
|
Muralidharan-Chari V, Clancy J, Plou C, Romao M, Chavrier P, Raposo G and D'Souza-Schorey C: ARF6-regulated shedding of tumor cell-derived plasma membrane microvesicles. Curr Biol. 19:1875–1885. 2009.PubMed/NCBI View Article : Google Scholar | |
|
Sabry D, El-Deek SEM, Maher M, El-Baz MAH, El-Bader HM, Amer E, Hassan EA, Fathy W and El-Deek HEM: Role of miRNA-210, miRNA-21 and miRNA-126 as diagnostic biomarkers in colorectal carcinoma: Impact of HIF-1α-VEGF signaling pathway. Mol Cell Biochem. 454:177–189. 2019.PubMed/NCBI View Article : Google Scholar | |
|
Cheng J, Chen Y, Zhao P, Liu X, Dong J, Li J, Huang C, Wu R and Lv Y: Downregulation of miRNA-638 promotes angiogenesis and growth of hepatocellular carcinoma by targeting VEGF. Oncotarget. 7:30702–30711. 2016.PubMed/NCBI View Article : Google Scholar | |
|
Yamada N, Tsujimura N, Kumazaki M, Shinohara H, Taniguchi K, Nakagawa Y, Naoe T and Akao Y: Colorectal cancer cell-derived microvesicles containing microRNA-1246 promote angiogenesis by activating Smad 1/5/8 signaling elicited by PML down-regulation in endothelial cells. Biochim Biophys Acta. 1839:1256–1272. 2014.PubMed/NCBI View Article : Google Scholar | |
|
Tisdale MJ: Cancer cachexia. Curr Opin Gastroenterol. 26:146–151. 2010.PubMed/NCBI View Article : Google Scholar | |
|
Bilodeau PA, Coyne ES and Wing SS: The ubiquitin proteasome system in atrophying skeletal muscle: Roles and regulation. Am J Physiol Cell Physiol. 311:C392–C403. 2016.PubMed/NCBI View Article : Google Scholar | |
|
Reed SA, Sandesara PB, Senf SM and Judge AR: Inhibition of FoxO transcriptional activity prevents muscle fiber atrophy during cachexia and induces hypertrophy. FASEB J. 26:987–1000. 2012.PubMed/NCBI View Article : Google Scholar | |
|
Xu J, Li R, Workeneh B, Dong Y, Wang X and Hu Z: Transcription factor FoxO1, the dominant mediator of muscle wasting in chronic kidney disease, is inhibited by microRNA-486. Kidney Int. 82:401–411. 2012.PubMed/NCBI View Article : Google Scholar | |
|
Suzuki T and Springer J: MicroRNAs in muscle wasting. J Cachexia Sarcopenia Muscle. 9:1209–1212. 2018.PubMed/NCBI View Article : Google Scholar | |
|
Sutandyo N: The role of microRNA in cancer cachexia and muscle wasting: A review article. Caspian J Intern Med. 12:124–128. 2021.PubMed/NCBI View Article : Google Scholar | |
|
Brzeszczyńska J, Brzeszczyński F, Hamilton DF, McGregor R and Simpson AHRW: Role of microRNA in muscle regeneration and diseases related to muscle dysfunction in atrophy, cachexia, osteoporosis, and osteoarthritis. Bone Joint Res. 9:798–807. 2020.PubMed/NCBI View Article : Google Scholar | |
|
Zhou L, Zhang T, Shao W, Lu R, Wang L, Liu H, Jiang B, Li S, Zhuo H, Wang S, et al: Amiloride ameliorates muscle wasting in cancer cachexia through inhibiting tumor-derived exosome release. Skeletal muscle. 11(17)2021.PubMed/NCBI View Article : Google Scholar | |
|
van de Worp WRPH, Schols AMWJ, Schols AMWJ, Dingemans AC, Op den Kamp CMH, Degens JHRJ, Kelders MCJM, Coort S, Woodruff HC, Kratassiouk G, et al: Identification of microRNAs in skeletal muscle associated with lung cancer cachexia. J Cachexia Sarcopenia Muscle. 11:452–463. 2020.PubMed/NCBI View Article : Google Scholar | |
|
Fernandez GJ, Ferreira JH, Vechetti IJ Jr, de Moraes LN, Cury SS, Freire PP, Gutiérrez J, Ferretti R, Dal-Pai-Silva M, Rogatto SR and Carvalho RF: MicroRNA-mRNA Co-sequencing identifies transcriptional and post-transcriptional regulatory networks underlying muscle wasting in cancer cachexia. Front Genet. 11(541)2020.PubMed/NCBI View Article : Google Scholar | |
|
Daas SI, Rizeq BR and Nasrallah GK: Adipose tissue dysfunction in cancer cachexia. J Cell Physiol. 234:13–22. 2018.PubMed/NCBI View Article : Google Scholar | |
|
Petruzzelli M, Schweiger M, Schreiber R, Campos-Olivas R, Tsoli M, Allen J, Swarbrick M, Rose-John S, Rincon M, Robertson G, et al: A switch from white to brown fat increases energy expenditure in cancer-associated cachexia. Cell Metab. 20:433–447. 2014.PubMed/NCBI View Article : Google Scholar | |
|
Neves RX, Rosa-Neto JC, Yamashita AS, Matos-Neto EM, Riccardi DM, Lira FS, Batista ML Jr and Seelaender M: White adipose tissue cells and the progression of cachexia: Inflammatory pathways. J Cachexia Sarcopenia Muscle. 7:193–203. 2016.PubMed/NCBI View Article : Google Scholar | |
|
Camargo RG, Riccardi DM, Ribeiro HQ, Carnevali LC Jr, de Matos-Neto EM, Enjiu L, Neves RX, Lima JD, Figuerêdo RG, de Alcântara PS, et al: NF-κBp65 and expression of its pro-inflammatory target genes are upregulated in the subcutaneous adipose tissue of cachectic cancer patients. Nutrients. 7:4465–4479. 2015.PubMed/NCBI View Article : Google Scholar | |
|
Aswad H, Forterre A, Wiklander OP, Vial G, Danty-Berger E, Jalabert A, Lamazière A, Meugnier E, Pesenti S, Ott C, et al: Exosomes participate in the alteration of muscle homeostasis during lipid-induced insulin resistance in mice. Diabetologia. 57:2155–2164. 2014.PubMed/NCBI View Article : Google Scholar | |
|
Kulyté A, Lorente-Cebrián S, Gao H, Mejhert N, Agustsson T, Arner P, Rydén M and Dahlman I: MicroRNA profiling links miR-378 to enhanced adipocyte lipolysis in human cancer cachexia. Am J Physiol Endocrinol Metab. 306:E267–E274. 2014.PubMed/NCBI View Article : Google Scholar | |
|
Chen X, Ba Y, Ma L, Cai X, Yin Y, Wang K, Guo J, Zhang Y, Chen J, Guo X, et al: Characterization of microRNAs in serum: A novel class of biomarkers for diagnosis of cancer and other diseases. Cell Res. 18:997–1006. 2008.PubMed/NCBI View Article : Google Scholar | |
|
Donzelli S, Farneti A, Marucci L, Ganci F, Sacconi A, Strano S, Sanguineti G and Blandino G: Non-coding RNAs as putative biomarkers of cancer-associated cachexia. Front Cell Dev Biol. 8(257)2020.PubMed/NCBI View Article : Google Scholar | |
|
Hamaguchi Y, Kaido T, Okumura S, Kobayashi A, Hammad A, Tamai Y, Inagaki N and Uemoto S: Proposal for new diagnostic criteria for low skeletal muscle mass based on computed tomography imaging in Asian adults. Nutrition. 32:1200–1205. 2016.PubMed/NCBI View Article : Google Scholar | |
|
Kaido T: Selection criteria and current issues in liver transplantation for hepatocellular carcinoma. Liver Cancer. 5:121–127. 2016.PubMed/NCBI View Article : Google Scholar | |
|
Okugawa Y, Toiyama Y, Hur K, Yamamoto A, Yin C, Ide S, Kitajima T, Fujikawa H, Yasuda H, Koike Y, et al: Circulating miR-203 derived from metastatic tissues promotes myopenia in colorectal cancer patients. J Cachexia Sarcopenia Muscle. 10:536–548. 2019.PubMed/NCBI View Article : Google Scholar | |
|
Okugawa Y, Yao L, Toiyama Y, Yamamoto A, Shigemori T, Yin C, Omura Y, Ide S, Kitajima T, Shimura T, et al: Prognostic impact of sarcopenia and its correlation with circulating miR-21 in colorectal cancer patients. Oncol Rep. 39:1555–1564. 2018.PubMed/NCBI View Article : Google Scholar | |
|
Wang H and Wang B: Extracellular vesicle microRNAs mediate skeletal muscle myogenesis and disease. Biomed Rep. 5:296–300. 2016.PubMed/NCBI View Article : Google Scholar | |
|
Wu Q, Sun S, Li Z, Yang Q, Li B, Zhu S, Wang L, Wu J, Yuan J, Yang C, et al: Tumour-originated exosomal miR-155 triggers cancer-associated cachexia to promote tumour progression. Mol Cancer. 17(155)2018.PubMed/NCBI View Article : Google Scholar | |
|
Chitti SV, Fonseka P and Mathivanan S: Emerging role of extracellular vesicles in mediating cancer cachexia. Biochem Soc Trans. 46:1129–1136. 2018.PubMed/NCBI View Article : Google Scholar | |
|
Du G, Zhang Y, Hu S, Zhou X and Li Y: Non-coding RNAs in exosomes and adipocytes cause fat loss during cancer cachexia. Noncoding RNA Res. 6:80–85. 2021.PubMed/NCBI View Article : Google Scholar | |
|
Li L, Liu H, Tao W, Wen S, Fu X and Yu S: Pharmacological inhibition of HMGB1 prevents muscle wasting. Front Pharmacol. 12(731386)2021.PubMed/NCBI View Article : Google Scholar | |
|
Wan Z, Chen X, Gao X, Dong Y, Zhao Y, Wei M, Fan W, Yang G and Liu L: Chronic myeloid leukemia-derived exosomes attenuate adipogenesis of adipose derived mesenchymal stem cells via transporting miR-92a-3p. J Cell Physiol. 234:21274–21283. 2019.PubMed/NCBI View Article : Google Scholar | |
|
Köberle V, Kronenberger B, Pleli T, Trojan J, Imelmann E, Peveling-Oberhag J, Welker MW, Elhendawy M, Zeuzem S, Piiper A and Waidmann O: Serum microRNA-1 and microRNA-122 are prognostic markers in patients with hepatocellular carcinoma. Eur J Cancer. 49:3442–3449. 2013.PubMed/NCBI View Article : Google Scholar | |
|
Powrózek T, Mlak R, Brzozowska A, Mazurek M, Gołębiowski P and Małecka-Massalska T: MiRNA-130a significantly improves accuracy of SGA Nutritional assessment tool in prediction of malnutrition and cachexia in radiotherapy-treated head and neck cancer patients. Cancers (Basel). 10(294)2018.PubMed/NCBI View Article : Google Scholar | |
|
Chen D, Goswami CP, Burnett RM, Anjanappa M, Bhat-Nakshatri P, Muller W and Nakshatri H: Cancer affects microRNA expression, release, and function in cardiac and skeletal muscle. Cancer Res. 74:4270–4281. 2014.PubMed/NCBI View Article : Google Scholar | |
|
Lin J, Li J, Huang B, Liu J, Chen X, Chen XM, Xu YM, Huang LF and Wang XZ: Exosomes: Novel biomarkers for clinical diagnosis. ScientificWorldJournal. 2015(657086)2015.PubMed/NCBI View Article : Google Scholar | |
|
Belli R, Ferraro E, Molfino A, Carletti R, Tambaro F, Costelli P and Muscaritoli M: Liquid biopsy for cancer cachexia: Focus on muscle-derived microRNAs. Int J Mol Sci. 22(9007)2021.PubMed/NCBI View Article : Google Scholar | |
|
Li BS, Zhao YL, Guo G, Li W, Zhu ED, Luo X, Mao XH, Zou QM, Yu PW, Zuo QF, et al: Plasma microRNAs, miR-223, miR-21 and miR-218, as novel potential biomarkers for gastric cancer detection. PLoS One. 7(e41629)2012.PubMed/NCBI View Article : Google Scholar | |
|
Schrauder MG, Strick R, Schulz-Wendtland R, Strissel PL, Kahmann L, Loehberg CR, Lux MP, Jud SM, Hartmann A, Hein A, et al: Circulating micro-RNAs as potential blood-based markers for early stage breast cancer detection. PLoS One. 7(e29770)2012.PubMed/NCBI View Article : Google Scholar | |
|
Wang J, Chen J, Chang P, LeBlanc A, Li D, Abbruzzesse JL, Frazier ML, Killary AM and Sen S: MicroRNAs in plasma of pancreatic ductal adenocarcinoma patients as novel blood-based biomarkers of disease. Cancer Prev Res (Phila). 2:807–813. 2009.PubMed/NCBI View Article : Google Scholar | |
|
Kottorou A, Dimitrakopoulos FI and Tsezou A: Non-coding RNAs in cancer-associated cachexia: Clinical implications and future perspectives. Transl Oncol. 14(101101)2021.PubMed/NCBI View Article : Google Scholar | |
|
Yao P, Potdar AA, Arif A, Ray PS, Mukhopadhyay R, Willard B, Xu Y, Yan J, Saidel GM and Fox PL: Coding region polyadenylation generates a truncated tRNA synthetase that counters translation repression. Cell. 149:88–100. 2012.PubMed/NCBI View Article : Google Scholar | |
|
Gao P, Niu N, Wei T, Tozawa H, Chen X, Zhang C, Zhang J, Wada Y, Kapron CM and Liu J: The roles of signal transducer and activator of transcription factor 3 in tumor angiogenesis. Oncotarget. 8:69139–69161. 2017.PubMed/NCBI View Article : Google Scholar | |
|
Margolis LM and Rivas DA: Potential Role of MicroRNA in the anabolic capacity of skeletal muscle with aging. Exerc Sport Sci Rev. 46:86–91. 2018.PubMed/NCBI View Article : Google Scholar | |
|
Hou B, Xu S, Xu Y, Gao Q, Zhang C, Liu L, Yang H, Jiang X and Che Y: Grb2 binds to PTEN and regulates its nuclear translocation to maintain the genomic stability in DNA damage response. Cell Death Dis. 10(546)2019.PubMed/NCBI View Article : Google Scholar | |
|
Carr RM, Enriquez-Hesles E, Olson RL, Jatoi A, Doles J and Fernandez-Zapico ME: Epigenetics of cancer-associated muscle catabolism. Epigenomics. 9:1259–1265. 2017.PubMed/NCBI View Article : Google Scholar | |
|
György B, Hung ME, Breakefield XO and Leonard JN: Therapeutic applications of extracellular vesicles: Clinical promise and open questions. Annu Rev Pharmacol Toxicol. 55:439–464. 2015.PubMed/NCBI View Article : Google Scholar | |
|
Kalra H, Drummen GP and Mathivanan S: Focus on extracellular vesicles: Introducing the next small big thing. Int J Mol Sci. 17(170)2016.PubMed/NCBI View Article : Google Scholar | |
|
Terasawa K, Shimizu K and Tsujimoto G: Synthetic Pre-miRNA-Based shRNA as Potent RNAi Triggers. J Nucleic Acids. 2011(131579)2011.PubMed/NCBI View Article : Google Scholar | |
|
Bonneau E, Neveu B, Kostantin E, Tsongalis GJ and De Guire V: How close are miRNAs from clinical practice? A perspective on the diagnostic and therapeutic market. EJIFCC. 30:114–127. 2019.PubMed/NCBI | |
|
van Zandwijk N, Pavlakis N, Kao SC, Linton A, Boyer MJ, Clarke S, Huynh Y, Chrzanowska A, Fulham MJ, Bailey DL, et al: Safety and activity of microRNA-loaded minicells in patients with recurrent malignant pleural mesothelioma: A first-in-man, phase 1, open-label, dose-escalation study. Lancet Oncol. 18:1386–1396. 2017.PubMed/NCBI View Article : Google Scholar | |
|
Ebner N, Anker SD and von Haehling S: Recent developments in the field of cachexia, sarcopenia, and muscle wasting: Highlights from the 12th cachexia conference. J Cachexia Sarcopenia Muscle. 11:274–285. 2020.PubMed/NCBI View Article : Google Scholar |
