MicroRNA‑143 increases cell apoptosis in myelodysplastic syndrome through the Fas/FasL pathway both in vitro and in vivo

Cui,Jiaqi; Wei,Chunmei; Deng,Linli; Kuang,Xingyi; Zhang,Zengtie; Pierides,Chryso; Chi,Jianxiang; Wang,Li

doi:10.3892/ijo.2018.4534

MicroRNA‑143 increases cell apoptosis in myelodysplastic syndrome through the Fas/FasL pathway both in vitro and in vivo

Authors:
- Jiaqi Cui
- Chunmei Wei
- Linli Deng
- Xingyi Kuang
- Zengtie Zhang
- Chryso Pierides
- Jianxiang Chi
- Li Wang
View Affiliations

Affiliations: Department of Hematology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P.R. China, Department of Pathology, Xi'an Jiao Tong University Health Science Center, Xi'an, Shaanxi 710061, P.R. China, Center for the Study of Haematological Malignancies, Karaiskakio Foundation, 2032 Nicosia, Cyprus
Published online on: August 22, 2018 https://doi.org/10.3892/ijo.2018.4534
Pages: 2191-2199

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Whilst the role of microRNA‑143 (miR‑143) in myelodysplastic syndrome (MDS) remains unclear, abnormally expressed microRNA‑143 has been detected in many types of cancer tissues. In this study, we describe a cohort study for the verification of miR‑143 expression, as well as the investigation of the molecular mechanisms of miR‑143 in MDS/acute myeloid leukaemia (AML). In a series of experiments, miR‑143 recombinant lentiviral vectors transformed into SKM‑1 cells were either overexpressed or knocked down, and the results illustrated that the overexpression of miR‑143 inhibited SKM‑1 cell growth, arrested the SKM‑1 cells in the G0/G1 phase, interfered with cell proliferation and induced cell apoptosis via the Fas/FasL pathway. Conversely, miR‑143 knockdown induced a decrease in the apoptosis and promoted the proliferation of SKM‑1 cells. Moreover, miR‑143 was shown to suppress MLLT3/AF9 expression by binding to its 3'‑UTR. Taken together, the findings of this study indicate that miR‑143 may be a critical regulator of MDS/AML cell carcinogenesis, acting as a potent antitumour molecular target for the diagnosis or treatment of cancers associated with the abnormal expression of MLLT3/AF9, hence facilitating the development of potential therapeutics against MDS/AML.

View Figures

View References

1	de Witte T, Bowen D, Robin M, Malcovati L, Niederwieser D, Yakoub-Agha I, Mufti GJ, Fenaux P, Sanz G, Martino R, et al: Allogeneic hematopoietic stem cell transplantation for MDS and CMML: Recommendations from an international expert panel. Blood. 129:1753–1762. 2017. View Article : Google Scholar : PubMed/NCBI
2	Pellagatti A and Boultwood J: The molecular pathogenesis of the myelodysplastic syndromes. Eur J Haematol. 95:3–15. 2015. View Article : Google Scholar : PubMed/NCBI
3	Mandal N: Bibliometric analysis of global publication output and collaboration structure study in microRNA research. Scientometrics. 98:2011–2037. 2014. View Article : Google Scholar
4	Kuang X, Chi J and Wang L: Deregulated microRNA expression and its pathogenetic implications for myelodysplastic syndromes. Hematology. 21:593–602. 2016. View Article : Google Scholar : PubMed/NCBI
5	Simmer F, Venderbosch S, Dijkstra JR, Vink-Börger EM, Faber C, Mekenkamp LJ, Koopman M, De Haan AF, Punt CJ and Nagtegaal ID: MicroRNA-143 is a putative predictive factor for the response to fluoropyrimidine-based chemotherapy in patients with metastatic colorectal cancer. Oncotarget. 6:22996–23007. 2015. View Article : Google Scholar : PubMed/NCBI
6	Hu Y, Ma Z, He Y, Liu W, Su Y and Tang Z: PART-1 functions as a competitive endogenous RNA for promoting tumor progression by sponging miR-143 in colorectal cancer. Biochem Biophys Res Commun. 490:317–323. 2017. View Article : Google Scholar : PubMed/NCBI
7	Yu B, Liu X and Chang H: MicroRNA-143 inhibits colorectal cancer cell proliferation by targeting MMP7. Minerva Med. 108:13–19. 2017.
8	Zhou P, Chen WG and Li XW: MicroRNA-143 acts as a tumor suppressor by targeting hexokinase 2 in human prostate cancer. Am J Cancer Res. 5:2056–2063. 2015.PubMed/NCBI
9	Rodríguez M, Bajo-Santos C, Hessvik NP, Lorenz S, Fromm B, Berge V, Sandvig K, Linē A and Llorente A: Identification of non-invasive miRNAs biomarkers for prostate cancer by deep sequencing analysis of urinary exosomes. Mol Cancer. 16:1562017. View Article : Google Scholar : PubMed/NCBI
10	Wang F, Liu J, Zou Y, Jiao Y, Huang Y, Fan L, Li X, Yu H, He C, Wei W, et al: MicroRNA-143-3p, up-regulated in H. pylori-positive gastric cancer, suppresses tumor growth, migration and invasion by directly targeting AKT2. Oncotarget. 8:28711–28724. 2017.PubMed/NCBI
11	Du F, Feng Y, Fang J and Yang M: MicroRNA-143 enhances chemosensitivity of Quercetin through autophagy inhibition via target GABARAPL1 in gastric cancer cells. Biomed Pharmacother. 74:169–177. 2015. View Article : Google Scholar : PubMed/NCBI
12	Li J, Wang X and Zhang Y and Zhang Y: E3 ubiquitin ligase isolated by differential display regulates cervical cancer growth in vitro and in vivo via microRNA-143. Exp Ther Med. 12:676–682. 2016. View Article : Google Scholar : PubMed/NCBI
13	Dong P, Xiong Y, Hanley SJB, Yue J and Watari H: Musashi-2, a novel oncoprotein promoting cervical cancer cell growth and invasion, is negatively regulated by p53-induced miR-143 and miR-107 activation. J Exp Clin Cancer Res. 36:1502017. View Article : Google Scholar : PubMed/NCBI
14	Chen JH, Yang R, Zhang W and Wang YP: Functions of microRNA-143 in the apoptosis, invasion and migration of naso-pharyngeal carcinoma. Exp Ther Med. 12:3749–3755. 2016. View Article : Google Scholar
15	He B, Xu Z, Chen J, Zheng D, Li A and Zhang LS: Upregulated microRNA-143 inhibits cell proliferation in human nasopha-ryngeal carcinoma. Oncol Lett. 12:5023–5028. 2016. View Article : Google Scholar
16	Li WH, Wu HJ, Li YX, Pan HG, Meng T and Wang X: MicroRNA-143 promotes apoptosis of osteosarcoma cells by caspase-3 activation via targeting Bcl-2. Biomed Pharmacother. 80:8–15. 2016. View Article : Google Scholar : PubMed/NCBI
17	Zhang H, Wang G, Ding C, Liu P, Wang R, Ding W, Tong D, Wu D, Li C, Wei Q, et al: Increased circular RNA UBAP2 acts as a sponge of miR-143 to promote osteosarcoma progression. Oncotarget. 8:61687–61697. 2017.PubMed/NCBI
18	Akao Y, Nakagawa Y, Iio A and Naoe T: Role of microRNA-143 in Fas-mediated apoptosis in human T-cell leukemia Jurkat cells. Leuk Res. 33:1530–1538. 2009. View Article : Google Scholar : PubMed/NCBI
19	Ozdogan H, Gur Dedeoglu B, Oztemur Islakoglu Y, Aydos A, Kose S, Atalay A, Yegin ZA, Avcu F, Uckan Cetinkaya D and Ilhan O: DICER1 gene and miRNA dysregulation in mesen-chymal stem cells of patients with myelodysplastic syndrome and acute myeloblastic leukemia. Leuk Res. 63:62–71. 2017. View Article : Google Scholar : PubMed/NCBI
20	Votavova H, Grmanova M, Dostalova Merkerova M, Belickova M, Vasikova A, Neuwirtova R and Cermak J: Differential expression of microRNAs in CD34⁺ cells of 5q- syndrome. J Hematol Oncol. 4:12011. View Article : Google Scholar
21	Dostalova Merkerova M, Krejcik Z, Votavova H, Belickova M, Vasikova A and Cermak J: Distinctive microRNA expression profiles in CD34⁺ bone marrow cells from patients with myelo-dysplastic syndrome. Eur J Hum Genet. 19:313–319. 2011. View Article : Google Scholar
22	Wang L, Luo J, Nian Q, Xiao Q, Yang Z and Liu L: Ribosomal protein S14 silencing inhibits growth of acute myeloid leukemia transformed from myelodysplastic syndromes via activating p53. Hematology. 19:225–231. 2014. View Article : Google Scholar
23	Liu Z, Ding K, Li L, Liu H, Wang Y, Liu C and Fu R: A novel histone deacetylase inhibitor Chidamide induces G0/G1 arrest and apoptosis in myelodysplastic syndromes. Biomed Pharmacother. 83:1032–1037. 2016. View Article : Google Scholar : PubMed/NCBI
24	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 25:402–408. 2001. View Article : Google Scholar
25	Tiscornia G, Singer O and Verma IM: Production and purification of lentiviral vectors. Nat Protoc. 1:241–245. 2006. View Article : Google Scholar
26	Proetzel G and Wiles MV: Mouse Models for Drug Discovery: Methods and Protocols. Humana Press; Totowa, NJ: pp. 2010
27	Wu L, Li X, Su J, He Q, Zhang X, Chang C and Pu Q: Efficacy and safety of CHG regimen (low-dose cytarabine, homoharringtonine with G-CSF priming) as induction chemotherapy for elderly patients with high-risk MDS or AML transformed from MDS. J Cancer Res Clin Oncol. 137:1563–1569. 2011. View Article : Google Scholar : PubMed/NCBI
28	Pramanik D, Campbell NR, Karikari C, Chivukula R, Kent OA, Mendell JT and Maitra A: Restitution of tumor suppressor microRNAs using a systemic nanovector inhibits pancreatic cancer growth in mice. Mol Cancer Ther. 10:1470–1480. 2011. View Article : Google Scholar : PubMed/NCBI
29	Guerenne L, Beurlet S, Said M, Gorombei P, Le Pogam C, Guidez F, de la Grange P, Omidvar N, Vanneaux V, Mills K, et al: GEP analysis validates high risk MDS and acute myeloid leukemia post MDS mice models and highlights novel dysregulated pathways. J Hematol Oncol. 9:52016. View Article : Google Scholar : PubMed/NCBI
30	Agarwal V, Bell GW, Nam JW and Bartel DP: Predicting effective microRNA target sites in mammalian mRNAs. eLife. 4:42015. View Article : Google Scholar
31	Zhou J, Chaudhry H, Zhong Y, Ali MM, Perkins LA, Owens WB, Morales JE, McGuire FR, Zumbrun EE, Zhang J, et al: Dysregulation in microRNA expression in peripheral blood mononuclear cells of sepsis patients is associated with immunopathology. Cytokine. 71:89–100. 2015. View Article : Google Scholar
32	Shen JZ, Zhang YY, Fu HY, Wu DS and Zhou HR: Overexpression of microRNA-143 inhibits growth and induces apoptosis in human leukemia cells. Oncol Rep. 31:2035–2042. 2014. View Article : Google Scholar : PubMed/NCBI
33	Lewis BP, Burge CB and Bartel DP: Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell. 120:15–20. 2005. View Article : Google Scholar : PubMed/NCBI
34	Chen X, Clark J, Wunderlich M, Fan C, Davis A, Chen S, Guan JL, Mulloy JC, Kumar A and Zheng Y: Autophagy is dispensable for Kmt2a/Mll-Mllt3/Af9 AML maintenance and anti-leukemic effect of chloroquine. Autophagy. 13:955–966. 2017. View Article : Google Scholar : PubMed/NCBI
35	Zhang T, Luo Y, Wang T and Yang JY: MicroRNA-297b-5p/3p target Mllt3/Af9 to suppress lymphoma cell proliferation, migration and invasion in vitro and tumor growth in nude mice. Leuk Lymphoma. 53:2033–2040. 2012. View Article : Google Scholar : PubMed/NCBI
36	Vogel T and Gruss P: Expression of leukaemia associated transcription factor Af9/Mllt3 in the cerebral cortex of the mouse. Gene Expr Patterns. 9:83–93. 2009. View Article : Google Scholar