Effects of miR‑181a on the biological function of multiple myeloma

Liu,Ni; Yang,Jingyu; Yuan,Ruili; Peng,Jing; Liu,Lina; Guo,Xuan

doi:10.3892/or.2019.7160

Effects of miR‑181a on the biological function of multiple myeloma

Authors:
- Ni Liu
- Jingyu Yang
- Ruili Yuan
- Jing Peng
- Lina Liu
- Xuan Guo
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Affiliations: Department of Clinical Laboratory, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China, Department of Clinical Laboratory, Xi'an Hospital of Traditional Chinese Medicine, Xi'an, Shaanxi 710021, P.R. China
Published online on: May 15, 2019 https://doi.org/10.3892/or.2019.7160
Pages: 291-300

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Abstract

The present study aimed to investigate the role of miR‑181a in multiple myeloma (MM) cell lines. Reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) was used to detect the expression of microRNA (miR)‑181a. The MM cell line RPMI 8226 stably transduced with miR‑181a mimics or inhibitor was established via lentiviral vectors. A Cell Counting Kit‑8 proliferation assay, flow cytometry and a Transwell assay were conducted to assess cell proliferation, cell cycle, apoptosis and invasion. The role of miR‑181a in MM tumor formation in vivo was assessed using a SCID Berge xenograft tumor model. The potential target genes of miR‑181a were predicted using bioinformatic tools, and the expression of a potential target gene of miR‑181a, neuro‑oncological ventral antigen‑1 (NOVA1) was detected by RT‑qPCR. miR‑181a was determined to be significantly upregulated in MM cells (P<0.001). Following silencing of miR‑181a via lentiviral‑mediated transduction, RPMI 8226 cells exhibited a significant decrease in the number of S phase cells, and proliferative and invasive abilities. In addition, apoptosis was significantly promoted. A total of nine cross‑target genes were pre‑selected via bioinformatics software, including NOVA1. The results revealed that miR‑181a inhibitor suppressed the expression of NOVA1 (t=26.951, P=0.001). In the xenograft tumor model of SCID Berge mice, miR‑181a knock down significantly inhibited tumor growth. Conversely, these effects were reversed in response to miR‑181 mimics. In summary, miR‑181a was determined to be upregulated in MM cells, and may affect the biological function of cancer cells. The underlying mechanism may comprise the regulation of downstream target genes; however, further investigation is required.

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1	Li Y, Bai O, Liu C, Du Z, Wang X, Wang G and Li W: Association between hepatitis B virus infection and risk of multiple myeloma: A systematic review and meta-analysis. Intern Med J. 46:307–314. 2016. View Article : Google Scholar : PubMed/NCBI
2	Palumbo A and Anderson K: Multiple myeloma. N Engl J Med. 364:1046–1060. 2011. View Article : Google Scholar : PubMed/NCBI
3	Dürner J, Reinecker H and Csef H: Individual quality of life in patients with multiple myeloma. Springerplus. 2:3972013. View Article : Google Scholar : PubMed/NCBI
4	Nooka AK, Kastritis E, Dimopoulos MA and Lonial S: Treatment options for relapsed and refractory multiple myeloma. Blood. 125:3085–3099. 2015. View Article : Google Scholar : PubMed/NCBI
5	Patriarca F, Fanin R, Silvestri F, Damiani D and Baccarani M: Autologous stem cell transplantation in multiple myeloma: A single center experience. Haematologica. 83:477–479. 1998.PubMed/NCBI
6	Zhao Z, Ma X, Sung D, Li M, Kosti A, Lin G, Chen Y, Pertsemlidis A, Hsiao TH and Du L: microRNA-449a functions as a tumor suppressor in neuroblastoma through inducing cell differentiation and cell cycle arrest. RNA Biol. 12:538–554. 2015. View Article : Google Scholar : PubMed/NCBI
7	Ambros V: The functions of animal microRNAs. Nature. 431:350–355. 2004. View Article : Google Scholar : PubMed/NCBI
8	Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D, Sweet-Cordero A, Ebert BL, Mak RH, Ferrando AA, et al: MicroRNA expression profiles classify human cancers. Nature. 435:834–838. 2005. View Article : Google Scholar : PubMed/NCBI
9	Michael MZ, O'Connor SM, van Holst Pellekaan NG, Young GP and James RJ: Reduced accumulation of specific microRNAs in colorectal neoplasia. Mol Cancer Res. 1:882–891. 2003.PubMed/NCBI
10	Tutar Y: miRNA and cancer; Computational and experimental approaches. Curr Pharm Biotechnol. 15:4292014. View Article : Google Scholar : PubMed/NCBI
11	Deb B, Uddin A and Chakraborty S: miRNAs and ovarian cancer: An overview. J Cell Physiol. 233:3846–3854. 2018. View Article : Google Scholar : PubMed/NCBI
12	Chen CZ, Li L, Lodish HF and Bartel DP: MicroRNAs modulate hematopoietic lineage differentiation. Science. 303:83–86. 2004. View Article : Google Scholar : PubMed/NCBI
13	Liu G, Li Y and Gao XG: microRNA-181a is upregulated in human atherosclerosis plaques and involves in the oxidative stress-induced endothelial cell dysfunction through direct targeting Bcl-2. Eur Rev Med Pharmacol Sci. 20:3092–3100. 2016.PubMed/NCBI
14	Cao Y, Zhao D, Li P, Wang L, Qiao B, Qin X, Li L and Wang Y: MicroRNA-181a-5p impedes IL-17-induced nonsmall cell lung cancer proliferation and migration through targeting VCAM-1. Cell Physiol Biochem. 42:346–356. 2017. View Article : Google Scholar : PubMed/NCBI
15	Liu Z, Sun F, Hong Y, Liu Y, Fen M, Yin K, Ge X, Wang F, Chen X and Guan W: MEG2 is regulated by miR-181a-5p and functions as a tumour suppressor gene to suppress the proliferation and migration of gastric cancer cells. Mol Cancer. 16:1332017. View Article : Google Scholar : PubMed/NCBI
16	Su R, Lin HS, Zhang XH, Yin XL, Ning HM, Liu B, Zhai PF, Gong JN, Shen C, Song L, et al: MiR-181 family: Regulators of myeloid differentiation and acute myeloid leukemia as well as potential therapeutic targets. Oncogene. 34:3226–3239. 2015. View Article : Google Scholar : PubMed/NCBI
17	Lyu X, Li J, Yun X, Huang R, Deng X, Wang Y, Chen Y and Xiao G: miR-181a-5p, an inducer of Wnt-signaling, facilitates cell proliferation in acute lymphoblastic leukemia. Oncol Rep. 37:1469–1476. 2017. View Article : Google Scholar : PubMed/NCBI
18	Xiang T, Hu AX, Sun P, Liu G, Liu G and Xiao Y: Identification of four potential predicting miRNA biomarkers for multiple myeloma from published datasets. PeerJ. 5:e28312017. View Article : Google Scholar : PubMed/NCBI
19	Peng J, Thakur A, Zhang S, Dong Y, Wang X, Yuan R, Zhang K and Guo X: Expressions of miR-181a and miR-20a in RPMI 8226 cell line and their potential as biomarkers for multiple myeloma. Tumour Biol. 36:8545–8552. 2015. View Article : Google Scholar : PubMed/NCBI
20	Shen B, Zhang Y, Yu S, Yuan Y, Zhong Y, Lu J and Feng J: MicroRNA-339, an epigenetic modulating target is involved in human gastric carcinogenesis through targeting NOVA1. FEBS Lett. 589:3205–3211. 2015. View Article : Google Scholar : PubMed/NCBI
21	Yuan R, Liu N, Yang J, Peng J, Liu L and Guo X: The expression and role of miR-181a in multiple myeloma. Medicine (Baltimore). 97:e120812018. View Article : Google Scholar : PubMed/NCBI
22	Tassone G and Fidler SJ: Separation and cryopreservation of lymphocytes from spleen and lymph node. Methods Mol Biol. 882:351–357. 2012. View Article : Google Scholar : PubMed/NCBI
23	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 : PubMed/NCBI
24	Xin Y, Li Z, Zheng H, Ho J, Chan MTV and Wu WKK: Neuro-oncological ventral antigen 1 (NOVA1): Implications in neurological diseases and cancers. Cell Prolif. 50:2017. View Article : Google Scholar :
25	Zhang YA, Liu HN, Zhu JM, Zhang DY, Shen XZ and Liu TT: RNA binding protein Nova1 promotes tumor growth in vivo and its potential mechanism as an oncogene may due to its interaction with GABA_A Receptor-g2. J Biomed Sci. 23:712016. View Article : Google Scholar : PubMed/NCBI
26	Zhou H and Wu L: The development and function of dendritic cell populations and their regulation by miRNAs. Protein Cell. 8:501–513. 2017. View Article : Google Scholar : PubMed/NCBI
27	Bartel DP: MicroRNAs: Genomics, biogenesis, mechanism, and function. Cell. 116:281–297. 2004. View Article : Google Scholar : PubMed/NCBI
28	Zhang Y, Yang P and Wang XF: Microenvironmental regulation of cancer metastasis by miRNAs. Trends Cell Biol. 24:153–160. 2014. View Article : Google Scholar : PubMed/NCBI
29	Shin VY and Chu KM: MiRNA as potential biomarkers and therapeutic targets for gastric cancer. World J Gastroenterol. 20:10432–10439. 2014. View Article : Google Scholar : PubMed/NCBI
30	Calin GA and Croce CM: MicroRNA signatures in human cancers. Nat Rev Cancer. 6:857–866. 2006. View Article : Google Scholar : PubMed/NCBI
31	Manikandan J, Aarthi JJ, Kumar SD and Pushparaj PN: Oncomirs: The potential role of non-coding microRNAs in understanding cancer. Bioinformation. 2:330–334. 2008. View Article : Google Scholar : PubMed/NCBI
32	Miska EA: How microRNAs control cell division, differentiation and death. Curr Opin Genet Dev. 15:563–568. 2005. View Article : Google Scholar : PubMed/NCBI
33	Yu W, Li L, Zheng F, Yang W, Zhao S, Tian C, Yin W, Chen Y, Guo W, Zou L and Deng W: β-catenin cooperates with CREB binding protein to promote the growth of tumor cells. Cell Physiol Biochem. 44:467–478. 2017. View Article : Google Scholar : PubMed/NCBI
34	Yang M, Zhai X, Ge T, Yang C and Lou G: miR-181a-5p promotes proliferation and invasion and inhibits apoptosis of cervical cancer cells via regulating inositol polyphosphate-5-phosphatase A (INPP5A). Oncol Res. 26:703–712. 2018. View Article : Google Scholar : PubMed/NCBI
35	Han P, Li JW, Zhang BM, Lv JC, Li YM, Gu XY, Yu ZW, Jia YH, Bai XF, Li L, et al: The lncRNA CRNDE promotes colorectal cancer cell proliferation and chemoresistance via miR-181a-5p-mediated regulation of Wnt/β-catenin signaling. Mol Cancer. 16:92017. View Article : Google Scholar : PubMed/NCBI
36	Arora S and Tandon S: Achyranthes aspera root extracts induce human colon cancer cell (COLO-205) death by triggering the mitochondrial apoptosis pathway and S phase cell cycle arrest. ScientificWorldJournal. 2014:1296972014. View Article : Google Scholar : PubMed/NCBI
37	Janowski BA, Younger ST, Hardy DB, Ram R, Huffman KE and Corey DR: Activating gene expression in mammalian cells with promoter-targeted duplex RNAs. Nat Chem Biol. 3:166–173. 2007. View Article : Google Scholar : PubMed/NCBI
38	Li LC, Okino ST, Zhao H, Pookot D, Place RF, Urakami S, Enokida H and Dahiya R: Small dsRNAs induce transcriptional activation in human cells. Proc Natl Acad Sci USA. 103:17337–17342. 2006. View Article : Google Scholar : PubMed/NCBI
39	Place RF, Li LC, Pookot D, Noonan EJ and Dahiya R: MicroRNA-373 induces expression of genes with complementary promoter sequences. Proc Natl Acad Sci USA. 105:1608–1613. 2008. View Article : Google Scholar : PubMed/NCBI