The diagnostic and prognostic value of plasma microRNA‑125b‑5p in patients with multiple myeloma

Jiang,Yanxia; Luan,Yajing; Chang,Hong; Chen,Guoan

doi:10.3892/ol.2018.9128

The diagnostic and prognostic value of plasma microRNA‑125b‑5p in patients with multiple myeloma

Authors:
- Yanxia Jiang
- Yajing Luan
- Hong Chang
- Guoan Chen
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Affiliations: Hematology Department, The 1st Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330000, P.R. China, Department of Basic Medical Sciences, Tianjin Medical University, Tianjin 300000, P.R. China, Division of Molecular and Cellular Biology, Toronto General Research Institute, Toronto, ON M5G 2C4, Canada
Published online on: July 11, 2018 https://doi.org/10.3892/ol.2018.9128
Pages: 4001-4007

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Abstract

Aberrant expression of microRNAs (miRNAs) contributes to the progression and outcomes of several types of tumor, while circulating miRNAs have been reported to act as biomarkers for several types of cancer. To identify specific circulating miRNAs associated with multiple myeloma (MM), a miRNA microarray analysis was used, which identified 8 upregulated miRNAs and 4 downregulated miRNAs in the plasma of 6 patients with MM compared with 6 healthy individuals. Based on the microarray results, the 8 miRNAs (miR‑125b‑5p, miR‑483‑3p, miR‑4326, miR‑6894‑3p, miR‑4498, miR‑490‑3p, miR‑7155‑5p and miR‑937‑3p), which were notably upregulated in MM patients were chosen for a second clinical study in 20 healthy controls and 35 patients with MM using reverse transcription‑ quantitative polymerase chain reaction. Receiver operating characteristic analysis demonstrated that miR‑125b‑5p and miR‑490‑3p displayed considerable diagnostic accuracy for MM with areas under the curve of 0.954 (P<0.001) and 0.866 (P=0.028), respectively. In addition, the plasma level of miR‑125b‑5p was associated with the international staging system disease stage. Patients with higher levels of plasma miR‑125b‑5p had a significantly shorter event‑free survival. However, miR‑490‑3p levels were not associated with event‑free survival (P>0.05). In summary, miR‑125b‑5p may serve as a potential clinical biomarker for MM.

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1	Sonneveld P, Avet-Loiseau H, Lonial S, Usmani S, Siegel D, Anderson KC, Chng WJ, Moreau P, Attal M, Kyle RA, et al: Treatment of multiple myeloma with high-risk cytogenetics: A consensus of the International myeloma working group. Blood. 127:2955–2962. 2016. View Article : Google Scholar : PubMed/NCBI
2	Abdi J, Chen G and Chang H: Erratum: Drug resistance in multiple myeloma: Latest findings and new concepts on molecular mechanisms. Oncotarget. 6:73642015.PubMed/NCBI
3	Mimura N, Hideshima T and Anderson KC: Novel therapeutic strategies for multiple myeloma. Exp Hematol. 43:732–741. 2015. View Article : Google Scholar : PubMed/NCBI
4	Liao TL, Chen YM, Hsieh CW, Chen HH, Lee HC, Hung WT, Tang KT and Chen DY: Upregulation of circulating microRNA-134 in adult-onset Still's disease and its use as potential biomarker. Sci Rep. 7:42142017. View Article : Google Scholar : PubMed/NCBI
5	Pilli T, Cantara S, Marzocchi C, Cardinale S, Santini C, Cevenini G and Pacini F: Diagnostic value of circulating microRNA-95 and −190 in the differential diagnosis of thyroid nodules: A validation study in 1000 consecutive patients. Thyroid. 27:1053–1057. 2017. View Article : Google Scholar : PubMed/NCBI
6	Bartel DP: MicroRNAs: Genomics, biogenesis, mechanism, and function. Cell. 116:281–297. 2004. View Article : Google Scholar : PubMed/NCBI
7	Zhang B, Pan X, Cobb GP and Anderson TA: microRNAs as oncogenes and tumor suppressors. Dev Biol. 302:1–12. 2007. View Article : Google Scholar : PubMed/NCBI
8	Zheng P, Guo H, Li G, Han S, Luo F and Liu Y: PSMB4 promotes multiple myeloma cell growth by activating NF-κB-miR-21 signaling. Biochem Biophys Res Commun. 458:328–333. 2015. View Article : Google Scholar : PubMed/NCBI
9	Shen X, Guo Y, Yu J, Qi J, Shi W, Wu X, Ni H and Ju S: miRNA-202 in bone marrow stromal cells affects the growth and adhesion of multiple myeloma cells by regulating B cell-activating factor. Clin Exp Med. 16:307–316. 2016. View Article : Google Scholar : PubMed/NCBI
10	Shi XB, Xue L, Yang J, Ma AH, Zhao J, Xu M, Tepper CG, Evans CP, Kung HJ and deVere White RW: An androgen-regulated miRNA suppresses Bak1 expression and induces androgen-independent growth of prostate cancer cells. Proc Natl Acad Sci USA. 104:19983–19988. 2007. View Article : Google Scholar : PubMed/NCBI
11	Bousquet M, Quelen C, Rosati R, Mansat-De Mas V, La Starza R, Bastard C, Lippert E, Talmant P, Lafage-Pochitaloff M, Leroux D, et al: Myeloid cell differentiation arrest by miR-125b-1 in myelodysplastic syndrome and acute myeloid leukemia with the t(2;11) (p21;q23) translocation. J Exp Med. 205:2499–2506. 2008. View Article : Google Scholar : PubMed/NCBI
12	Anderson KC: Progress and paradigms in multiple myeloma. Clin Cancer Res. 22:5419–5427. 2016. View Article : Google Scholar : PubMed/NCBI
13	Riazalhosseini B, Mohamed R, Apalasamy YD, Langmia IM and Mohamed Z: Circulating microRNA as a marker for predicting liver disease progression in patients with chronic hepatitis B. Rev Soc Bras Med Trop. 50:161–166. 2017. View Article : Google Scholar : PubMed/NCBI
14	Wu L, Hu B, Zhao B, Liu Y, Yang Y, Zhang L and Chen J: Circulating microRNA-422a is associated with lymphatic metastasis in lung cancer. Oncotarget. 8:42173–42188. 2017.PubMed/NCBI
15	Xu G, Zhang Z, Zhang L, Chen Y, Li N, Lv Y, Li Y and Xu X: miR-4326 promotes lung cancer cell proliferation through targeting tumor suppressor APC2. Mol Cell Biochem. 443:151–157. 2018. View Article : Google Scholar : PubMed/NCBI
16	Bertero T, Gastaldi C, Bourget-Ponzio I, Imbert V, Loubat A, Selva E, Busca R, Mari B, Hofman P, Barbry P, et al: miR-483-3p controls proliferation in wounded epithelial cells. FASEB J. 25:3092–3105. 2011. View Article : Google Scholar : PubMed/NCBI
17	Morelli E, Leone E, Cantafio ME, Di Martino MT, Amodio N, Biamonte L, Gullà A, Foresta U, Pitari MR, Botta C, et al: Selective targeting of IRF4 by synthetic microRNA-125b-5p mimics induces anti-multiple myeloma activity in vitro and in vivo. Leukemia. 29:2173–2183. 2015. View Article : Google Scholar : PubMed/NCBI
18	Gu H, Yang T, Fu S, Chen X, Guo L and Ni Y: MicroRNA-490-3p inhibits proliferation of A549 lung cancer cells by targeting CCND1. Biochem Biophys Res Commun. 444:104–108. 2014. View Article : Google Scholar : PubMed/NCBI
19	Zheng K, Zhou X, Yu J, Li Q, Wang H, Li M, Shao Z, Zhang F, Luo Y, Shen Z, et al: Epigenetic silencing of miR-490-3p promotes development of an aggressive colorectal cancer phenotype through activation of the Wnt/β-catenin signaling pathway. Cancer Lett. 376:178–187. 2016. View Article : Google Scholar : PubMed/NCBI
20	Zhou B, Wang Y, Jiang J, Jiang H, Song J, Han T, Shi J and Qiao H: The long noncoding RNA colon cancer-associated transcript-1/miR-490 axis regulates gastric cancer cell migration by targeting hnRNPA1. IUBMB Life. 68:201–210. 2016. View Article : Google Scholar : PubMed/NCBI
21	Zhang W, Zhang C, Chen H, Li L, Tu Y, Liu C, Shi S, Zen K and Liu Z: Evaluation of microRNAs miR-196a, miR-30a-5P, and miR-490 as biomarkers of disease activity among patients with FSGS. Clin J Am Soc Nephrol. 9:1545–1552. 2014. View Article : Google Scholar : PubMed/NCBI
22	Bloomston M, Frankel WL, Petrocca F, Volinia S, Alder H, Hagan JP, Liu CG, Bhatt D, Taccioli C and Croce CM: MicroRNA expression patterns to differentiate pancreatic adenocarcinoma from normal pancreas and chronic pancreatitis. JAMA. 297:1901–1908. 2007. View Article : Google Scholar : PubMed/NCBI
23	Ma Q, Chen Z, Jia G, Lu X, Xie X and Jin W: The histone demethylase PHF8 promotes prostate cancer cell growth by activating the oncomiR miR-125b. Onco Targets Ther. 8:1979–1988. 2015.PubMed/NCBI
24	Liu J, Guo B, Chen Z, Wang N, Iacovino M, Cheng J, Roden C, Pan W, Khan S, Chen S, et al: miR-125b promotes MLL-AF9-driven murine acute myeloid leukemia involving a VEGFA-mediated non-cell-intrinsic mechanism. Blood. 129:1491–1502. 2017. View Article : Google Scholar : PubMed/NCBI
25	Visone R, Pallante P, Vecchione A, Cirombella R, Ferracin M, Ferraro A, Volinia S, Coluzzi S, Leone V, Borbone E, et al: Specific microRNAs are downregulated in human thyroid anaplastic carcinomas. Oncogene. 26:7590–7595. 2007. View Article : Google Scholar : PubMed/NCBI
26	Veerla S, Lindgren D, Kvist A, Frigyesi A, Staaf J, Persson H, Liedberg F, Chebil G, Gudjonsson S, Borg A, et al: MiRNA expression in urothelial carcinomas: important roles of miR-10a, miR-222, miR-125b, miR-7 and miR-452 for tumor stage and metastasis, and frequent homozygous losses of miR-31. Int J Cancer. 124:2236–2242. 2009. View Article : Google Scholar : PubMed/NCBI
27	Xia HF, He TZ, Liu CM, Cui Y, Song PP, Jin XH and Ma X: MiR-125b expression affects the proliferation and apoptosis of human glioma cells by targeting Bmf. Cell Physiol Biochem. 23:347–358. 2009. View Article : Google Scholar : PubMed/NCBI
28	Le MT, Teh C, Shyh-Chang N, Xie H, Zhou B, Korzh V, Lodish HF and Lim B: MicroRNA-125b is a novel negative regulator of p53. Genes Dev. 23:862–876. 2009. View Article : Google Scholar : PubMed/NCBI
29	Murray MY, Rushworth SA, Zaitseva L, Bowles KM and Macewan DJ: Attenuation of dexamethasone-induced cell death in multiple myeloma is mediated by miR-125b expression. Cell Cycle. 12:2144–2153. 2013. View Article : Google Scholar : PubMed/NCBI
30	Chen H and Xu Z: Hypermethylation-associated silencing of miR-125a and miR-125b: A potential marker in colorectal cancer. Dis Markers. 2015:3450802015. View Article : Google Scholar : PubMed/NCBI
31	Wang H, Tan G, Dong L, Cheng L, Li K, Wang Z and Luo H: Circulating MiR-125b as a marker predicting chemoresistance in breast cancer. PLoS One. 7:e342102012. View Article : Google Scholar : PubMed/NCBI
32	Liu W, Hu J, Zhou K, Chen F, Wang Z, Liao B, Dai Z, Cao Y, Fan J and Zhou J: Serum exosomal miR-125b is a novel prognostic marker for hepatocellular carcinoma. Onco Targets Ther. 10:3843–3851. 2017. View Article : Google Scholar : PubMed/NCBI
33	Wong KY, Li Z, Zhang X, Leung GK, Chan GC and Chim CS: Epigenetic silencing of a long non-coding RNA KIAA0495 in multiple myeloma. Mol Cancer. 14:1752015. View Article : Google Scholar : PubMed/NCBI
34	Jairajpuri DS, Malalla ZH, Mahmood N and Almawi WY: Circulating microRNA expression as predictor of preeclampsia and its severity. Gene. 627:543–548. 2017. View Article : Google Scholar : PubMed/NCBI
35	Niu J, Xue A, Chi Y, Xue J, Wang W, Zhao Z, Fan M, Yang CH, Shao ZM, Pfeffer LM, et al: Induction of miRNA-181a by genotoxic treatments promotes chemotherapeutic resistance and metastasis in breast cancer. Oncogene. 35:1302–1313. 2016. View Article : Google Scholar : PubMed/NCBI