Hsa-miR-495 acts as a tumor suppressor gene in glioma via the negative regulation of MYB

Zhang,Benping; Yuan,Fei; Liu,Jie; Li,Yang; Zhou,Fucheng; Liu,Xuanxi; Hao,Zhen; Li,Qingsong; Zheng,Yongri; Wang,Weizhi

doi:10.3892/mmr.2016.5327

Hsa-miR-495 acts as a tumor suppressor gene in glioma via the negative regulation of MYB

Authors:
- Benping Zhang
- Fei Yuan
- Jie Liu
- Yang Li
- Fucheng Zhou
- Xuanxi Liu
- Zhen Hao
- Qingsong Li
- Yongri Zheng
- Weizhi Wang
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Affiliations: Department of Neurology, The Second Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China, Department of Neurosurgery, The Second Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China
Published online on: May 23, 2016 https://doi.org/10.3892/mmr.2016.5327
Pages: 977-982

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Abstract

MicroRNAs (miRNAs) are small non-coding RNA molecules that regulate gene expression at the post-transcriptional level. Previous studies have reported that there are causative links between the abnormal regulation of miRNAs and cancer development. Hsa‑miR‑495 has previously been demonstrated to be downregulated, and to function as a tumor suppressor, in numerous types of human cancer. However, the function and molecular mechanism of hsa‑miR‑495 in glioma remains unclear. In the current study, the expression and effects of hsa‑miR‑495 on glioma were evaluated. It was identified that the expression levels of hsa-miR-495 were downregulated in glioma tissues and cell lines. Furthermore, restoration of hsa-miR-495 inhibited glioma cell proliferation and invasion in vitro. Notably, a luciferase reporter assay revealed that hsa‑miR‑495 was able to directly target v‑myb avian myeloblastosis viral oncogene homolog (MYB) in glioma cells. In addition, an RNA interference assay indicated that MYB knockdown inhibited glioma cell proliferation and invasion in vitro. In conclusion, the results of the present study suggested that hsa‑miR‑495 may act as a tumor suppressor gene in glioma by directly inhibiting MYB expression, which may provide a novel therapeutic strategy for the treatment of glioma.

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1	Jemal A, Bray F, Center MM, Ferlay J, Ward E and Forman D: Global cancer statistics. CA Cancer J Clin. 61:69–90. 2011. View Article : Google Scholar : PubMed/NCBI
2	Osborn AG, Salzman KL, Thurnher MM, Rees JH and Castillo M: The new World Health Organization Classification of Central Nervous System Tumors: What can the neuroradiologist really say? AJNR Am J Neuroradiol. 33:795–802. 2012. View Article : Google Scholar
3	Furnari FB, Fenton T, Bachoo RM, Mukasa A, Stommel JM, Stegh A, Hahn WC, Ligon KL, Louis DN, Brennan C, et al: Malignant astrocytic glioma: Genetics, biology, and paths to treatment. Genes Dev. 21:2683–2710. 2007. View Article : Google Scholar : PubMed/NCBI
4	Ambros V: The functions of animal microRNAs. Nature. 431:350–355. 2004. View Article : Google Scholar : PubMed/NCBI
5	Kim VN: Small RNAs: Classification, biogenesis, and function. Mol Cells. 19:1–15. 2005.PubMed/NCBI
6	Shenouda SK and Alahari SK: MicroRNA function in cancer: Oncogene or a tumor suppressor? Cancer Metastasis Rev. 28:369–378. 2009. View Article : Google Scholar : PubMed/NCBI
7	Chu H, Chen X, Wang H, Du Y, Wang Y, Zang W, Li P, Li J, Chang J, Zhao G and Zhang G: MiR-495 regulates proliferation and migration in NSCLC by targeting MTA3. Tumour Biol. 35:3487–3494. 2014. View Article : Google Scholar
8	Li Z, Cao Y, Jie Z, Liu Y, Li Y, Li J, Zhu G, Liu Z, Tu Y, Peng G, et al: MiR-495 and miR-551a inhibit the migration and invasion of human gastric cancer cells by directly interacting with PRL-3. Cancer Lett. 323:41–47. 2012. View Article : Google Scholar : PubMed/NCBI
9	Jiang X, Huang H, Li Z, He C, Li Y, Chen P, Gurbuxani S, Arnovitz S, Hong GM, Price C, et al: MiR-495 is a tumor-suppressor microRNA down-regulated in MLL-rearranged leukemia. Proc Natl Acad Sci USA. 109:19397–19402. 2012. View Article : Google Scholar : PubMed/NCBI
10	Schmittgen TD and Livak KJ: Analyzing real-time PCR data by the comparative C(T) method. Nat Protoc. 3:1101–1108. 2008. View Article : Google Scholar : PubMed/NCBI
11	Wang W, Wu S, Shi Y, Miao Y, Luo X, Ji M, Yao K and He J: c-MYB regulates cell growth and DNA damage repair through modulating MiR-143. FEBS Lett. 589:555–564. 2015. View Article : Google Scholar : PubMed/NCBI
12	Liang J, Liu X, Xue H, Qiu B, Wei B and Sun K: MicroRNA-103a inhibits gastric cancer cell proliferation, migration and invasion by targeting c-Myb. Cell Prolif. 48:78–85. 2015. View Article : Google Scholar
13	Yang K, He M, Cai Z, Ni C, Deng J, Ta N, Xu J and Zheng J: A decrease in miR-150 regulates the malignancy of pancreatic cancer by targeting c-Myb and MUC4. Pancreas. 44:370–379. 2015.
14	Mets E, Van der Meulen J, Van Peer G, Boice M, Mestdagh P, Van de Walle I, Lammens T, Goossens S, De Moerloose B, Benoit Y, et al: MicroRNA-193b-3p acts as a tumor suppressor by targeting the MYB oncogene in T-cell acute lymphoblastic leukemia. Leukemia. 29:798–806. 2015. View Article : Google Scholar
15	Claes A, Idema AJ and Wesseling P: Diffuse glioma growth: A guerilla war. Acta Neuropathol. 114:443–458. 2007. View Article : Google Scholar : PubMed/NCBI
16	Huse JT and Holland EC: Targeting brain cancer: Advances in the molecular pathology of malignant glioma and medulloblastoma. Nat Rev Cancer. 10:319–331. 2010. View Article : Google Scholar : PubMed/NCBI
17	Hoelzinger DB, Demuth T and Berens ME: Autocrine factors that sustain glioma invasion and paracrine biology in the brain micro-environment. J Natl Cancer Inst. 99:1583–1593. 2007. View Article : Google Scholar : PubMed/NCBI
18	Zhang J, Gong X, Tian K, Chen D, Sun J, Wang G and Guo M: MiR-25 promotes glioma cell proliferation by targeting CDKN1C. Biomed Pharmacother. 71:7–14. 2015. View Article : Google Scholar : PubMed/NCBI
19	Xu D, Ma P, Gao G, Gui Y, Niu X and Jin B: MicroRNA-383 expression regulates proliferation, migration, invasion, and apoptosis in human glioma cells. Tumour Biol. 36:7743–7753. 2015. View Article : Google Scholar : PubMed/NCBI
20	Sun JY, Xiao WZ, Wang F, Wang YQ, Zhu YH, Wu YF, Miao ZL and Lin YC: MicroRNA-320 inhibits cell proliferation in glioma by targeting E2F1. Mol Med Rep. 12:2355–2359. 2015.PubMed/NCBI
21	Cai W, Li Q, Yang Z, Miao X, Wen Y, Huang S and Ouyang J: Expression of p53 upregulated modulator of apoptosis (PUMA) and C-myb in gallbladder adenocarcinoma and their pathological significance. Clin Transl Oncol. 15:818–824. 2013. View Article : Google Scholar : PubMed/NCBI
22	Chen RX, Xia YH, Xue TC and Ye SL: Transcription factor c-Myb promotes the invasion of hepatocellular carcinoma cells via increasing osteopontin expression. J Exp Clin Cancer Res. 29:1722010. View Article : Google Scholar : PubMed/NCBI
23	Lu H, Wang Y, Huang Y, Shi H, Xue Q, Yang S, He S and Wang H: Expression and prognostic role of c-Myb as a novel cell cycle protein in esophageal squamous cell carcinoma. Clin Transl Oncol. 15:796–801. 2013. View Article : Google Scholar : PubMed/NCBI
24	Tang R, Li J, Yue M, Liu Z, Feng S, Tang S and Wang T: A correlation analysis of miRNA-34a and its predicted target genes in leukemia. Mol Med Rep. 9:1283–1288. 2014.PubMed/NCBI