MicroRNA-103 suppresses glioma cell proliferation and invasion by targeting the brain-derived neurotrophic factor

Wang,Ling; Liu,Ying; Song,Jianwei

doi:10.3892/mmr.2017.8282

MicroRNA-103 suppresses glioma cell proliferation and invasion by targeting the brain-derived neurotrophic factor

Authors:
- Ling Wang
- Ying Liu
- Jianwei Song
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Affiliations: Department of Neurosurgery, Linyi People's Hospital, Linyi, Shandong 276000, P.R. China, Department of Emergency Surgery, Linyi People's Hospital, Linyi, Shandong 276000, P.R. China
Published online on: December 15, 2017 https://doi.org/10.3892/mmr.2017.8282
Pages: 4083-4089

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Abstract

Glioma is the most common and aggressive of malignant brain tumours. MicroRNAs (miRNAs/miRs) are involved in tumour development of various human cancers, including glioma. Therefore, miRNAs may have potential tumour diagnostic, prognostic and therapeutic values in human glioma. miR‑103 is abnormally expressed in various human cancer types. However, the detailed expression pattern, biological functions and underlying molecular mechanism of miR‑103 in glioma remain unclear. Therefore, the present study aimed to investigate the expression, biological roles and underlying mechanisms of miR‑103 in glioma. Results of the present study demonstrated that miR‑103 was significantly down‑regulated in glioma tissues and cell lines. Functional experiments demonstrated that miR‑103 overexpression inhibited the proliferation and invasion of glioma cells in vitro. Additionally, brain‑derived neurotrophic factor (BDNF) was identified as a direct functional target of miR‑103 in glioma. Furthermore, mRNA and protein expression levels of BDNF were highly upregulated in glioma tissues compared with normal brain tissues. Spearman's correlation analysis indicated a negative association between miR‑103 and BDNF mRNA expression levels in glioma tissues. Furthermore, rescue experiments demonstrated that BDNF up‑regulation reversed the suppressive effects of miR‑103 on glioma cell proliferation and invasion. Therefore, the authors of the present study hypothesized that the interaction between miR‑103 and BDNF serves a role in glioma progression and, in the future, may serve as a therapeutic target for glioma treatment.

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1	Goodenberger ML and Jenkins RB: Genetics of adult glioma. Cancer Genet. 205:613–621. 2012. View Article : Google Scholar : PubMed/NCBI
2	Buckner JC, Brown PD, O'Neill BP, Meyer FB, Wetmore CJ and Uhm JH: Central nervous system tumors. Mayo Clin Proc. 82:pp. 1271–1286. 2007; View Article : Google Scholar : PubMed/NCBI
3	Liu X, Wang S, Yuan A, Yuan X and Liu B: MicroRNA-140 represses glioma growth and metastasis by directly targeting ADAM9. Oncol Rep. 36:2329–2338. 2016. View Article : Google Scholar : PubMed/NCBI
4	Zhu GY, Shi BZ and Li Y: FoxM1 regulates Sirt1 expression in glioma cells. Eur Rev Med Pharmacol Sci. 18:205–211. 2014.PubMed/NCBI
5	Chen J, McKay RM and Parada LF: Malignant glioma: Lessons from genomics, mouse models, and stem cells. Cell. 149:36–47. 2012. View Article : Google Scholar : PubMed/NCBI
6	Stupp R, Mason WP, Van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, et al: Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 352:987–996. 2005. View Article : Google Scholar : PubMed/NCBI
7	Van Meir EG, Hadjipanayis CG, Norden AD, Shu HK, Wen PY and Olson JJ: Exciting new advances in neuro-oncology: The avenue to a cure for malignant glioma. CA Cancer J Clin. 60:166–193. 2010. View Article : Google Scholar : PubMed/NCBI
8	Lefranc F, Brotchi J and Kiss R: Possible future issues in the treatment of glioblastomas: Special emphasis on cell migration and the resistance of migrating glioblastoma cells to apoptosis. J Clin Oncol. 23:2411–2422. 2005. View Article : Google Scholar : PubMed/NCBI
9	Onishi M, Ichikawa T, Kurozumi K and Date I: Angiogenesis and invasion in glioma. Brain Tumor Pathol. 28:13–24. 2011. View Article : Google Scholar : PubMed/NCBI
10	Carrington JC and Ambros V: Role of microRNAs in plant and animal development. Science. 301:336–338. 2003. View Article : Google Scholar : PubMed/NCBI
11	Qin B, Yang H and Xiao B: Role of microRNAs in endothelial inflammation and senescence. Mol Biol Rep. 39:4509–4518. 2012. View Article : Google Scholar : PubMed/NCBI
12	Kotaja N: MicroRNAs and spermatogenesis. Fertil Steril. 101:1552–1562. 2014. View Article : Google Scholar : PubMed/NCBI
13	Imbar T and Eisenberg I: Regulatory role of microRNAs in ovarian function. Fertil Steril. 101:1524–1530. 2014. View Article : Google Scholar : PubMed/NCBI
14	Garg D and Cohen SM: miRNAs and aging: A genetic perspective. Ageing Res Rev. 17:3–8. 2014. View Article : Google Scholar : PubMed/NCBI
15	Dogini DB, Pascoal VD, Avansini SH, Vieira AS, Pereira TC and Lopes-Cendes I: The new world of RNAs. Genet Mol Biol. 37 1 Suppl:S285–S293. 2014. View Article : Google Scholar
16	Hong L, Ya-Wei L, Hai W, Qiang Z, Jun-Jie L, Huang A, Song-Tao Q and Yun-Tao L: MiR-519a functions as a tumor suppressor in glioma by targeting the oncogenic STAT3 pathway. J Neurooncol. 128:35–45. 2016. View Article : Google Scholar : PubMed/NCBI
17	Teoh SL and Das S: The role of MicroRNAs in diagnosis, prognosis, metastasis and resistant cases in breast cancer. Curr Pharm Des. 23:1845–1859. 2017. View Article : Google Scholar : PubMed/NCBI
18	Liu HT, Wang YW, Xing AY, Shi DB, Zhang H, Guo XY, Xu J and Gao P: Prognostic value of microRNA signature in patients with gastric cancers. Sci Rep. 7:428062017. View Article : Google Scholar : PubMed/NCBI
19	Dong F, Xu T, Shen Y, Zhong S, Chen S, Ding Q and Shen Z: Dysregulation of miRNAs in bladder cancer: Altered expression with aberrant biogenesis procedure. Oncotarget. 8:27547–27568. 2017.PubMed/NCBI
20	Liu L, Bi N, Wu L, Ding X, Men Y, Zhou W, Li L, Zhang W, Shi S, Song Y and Wang L: MicroRNA-29c functions as a tumor suppressor by targeting VEGFA in lung adenocarcinoma. Mol Cancer. 16:502017. View Article : Google Scholar : PubMed/NCBI
21	Chen Y, Gao DY and Huang L: In vivo delivery of miRNAs for cancer therapy: Challenges and strategies. Adv Drug Deliv Rev. 81:128–141. 2015. View Article : Google Scholar : PubMed/NCBI
22	Turner JD, Williamson R, Almefty KK, Nakaji P, Porter R, Tse V and Kalani MY: The many roles of microRNAs in brain tumor biology. Neurosurg Focus. 28:E32010. View Article : Google Scholar : PubMed/NCBI
23	Bartel DP: MicroRNAs: Genomics, biogenesis, mechanism, and function. Cell. 116:281–297. 2004. View Article : Google Scholar : PubMed/NCBI
24	Kong YW, Ferland-McCollough D, Jackson TJ and Bushell M: microRNAs in cancer management. Lancet Oncol. 13:e249–e258. 2012. View Article : Google Scholar : PubMed/NCBI
25	Geng L, Sun B, Gao B, Wang Z, Quan C, Wei F and Fang XD: MicroRNA-103 promotes colorectal cancer by targeting tumor suppressor DICER and PTEN. Int J Mol Sci. 15:8458–8472. 2014. View Article : Google Scholar : PubMed/NCBI
26	Yu D, Zhou H, Xun Q, Xu X, Ling J and Hu Y: microRNA-103 regulates the growth and invasion of endometrial cancer cells through the downregulation of tissue inhibitor of metalloproteinase 3. Oncol Lett. 3:1221–1226. 2012. View Article : Google Scholar : PubMed/NCBI
27	Fu X, Zhang W, Su Y, Lu L, Wang D and Wang H: MicroRNA-103 suppresses tumor cell proliferation by targeting PDCD10 in prostate cancer. Prostate. 76:543–551. 2016. View Article : Google Scholar : PubMed/NCBI
28	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
29	Neviani P and Fabbri M: Exosomic microRNAs in the tumor microenvironment. Front Med (Lausanne). 2:472015.PubMed/NCBI
30	Zhao Y, Pang D, Wang C, Zhong S and Wang S: MicroRNA-134 modulates glioma cell U251 proliferation and invasion by targeting KRAS and suppressing the ERK pathway. Tumour Biol. 37:11485–11493. 2016. View Article : Google Scholar : PubMed/NCBI
31	Tian LQ, Liu EQ, Zhu XD, Wang XG, Li J and Xu GM: MicroRNA-197 inhibits cell proliferation by targeting GAB2 in glioblastoma. Mol Med Rep. 13:4279–4288. 2016. View Article : Google Scholar : PubMed/NCBI
32	Garzon R, Calin GA and Croce CM: MicroRNAs in Cancer. Annu Rev Med. 60:167–179. 2009. View Article : Google Scholar : PubMed/NCBI
33	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 : PubMed/NCBI
34	Zheng YB, Xiao K, Xiao GC, Tong SL, Ding Y, Wang QS, Li SB and Hao ZN: MicroRNA-103 promotes tumor growth and metastasis in colorectal cancer by directly targeting LATS2. Oncol Lett. 12:2194–2200. 2016. View Article : Google Scholar : PubMed/NCBI
35	Wang X, Wu X, Yan L and Shao J: Serum miR-103 as a potential diagnostic biomarker for breast cancer. Nan Fang Yi Ke Da Xue Xue Bao. 32:631–634. 2012.(In Chinese). PubMed/NCBI
36	Xia W, Ni J, Zhuang J, Qian L, Wang P and Wang J: MiR-103 regulates hepatocellular carcinoma growth by targeting AKAP12. Int J Biochem Cell Biol. 71:1–11. 2016. View Article : Google Scholar : PubMed/NCBI
37	Choi B, Lee EJ, Shin MK, Park YS, Ryu MH, Kim SM, Kim EY, Lee HK and Chang EJ: Upregulation of brain-derived neurotrophic factor in advanced gastric cancer contributes to bone metastatic osteolysis by inducing long pentraxin 3. Oncotarget. 7:55506–55517. 2016. View Article : Google Scholar : PubMed/NCBI
38	Zhang SY, Hui LP, Li CY, Gao J, Cui ZS and Qiu XS: More expression of BDNF associates with lung squamous cell carcinoma and is critical to the proliferation and invasion of lung cancer cells. BMC Cancer. 16:1712016. View Article : Google Scholar : PubMed/NCBI
39	Moon A, Won KY, Lee JY, Kang I, Lee SK and Lee J: Expression of BDNF, TrkB, and p53 in early-stage squamous cell carcinoma of the uterine cervix. Pathology. 43:453–458. 2011. View Article : Google Scholar : PubMed/NCBI
40	Patani N, Jiang WG and Mokbel K: Brain-derived neurotrophic factor expression predicts adverse pathological & clinical outcomes in human breast cancer. Cancer Cell Int. 11:232011. View Article : Google Scholar : PubMed/NCBI
41	Yang X, Martin TA and Jiang WG: Biological influence of brain-derived neurotrophic factor (BDNF) on colon cancer cells. Exp Ther Med. 6:1475–1481. 2013. View Article : Google Scholar : PubMed/NCBI
42	Yang ZF, Ho DW, Lam CT, Luk JM, Lum CT, Yu WC, Poon RT and Fan ST: Identification of brain-derived neurotrophic factor as a novel functional protein in hepatocellular carcinoma. Cancer Res. 65:219–225. 2005.PubMed/NCBI
43	Tajbakhsh A, Mokhtari-Zaer A, Rezaee M, Afzaljavan F, Rivandi M, Hassanian SM, Ferns GA, Pasdar A and Avan A: Therapeutic potentials of BDNF/TrkB in breast cancer; current status and perspectives. J Cell Biochem. 118:2502–2515. 2017. View Article : Google Scholar : PubMed/NCBI
44	Yan Q, Yu HL and Li JT: Study on the expression of BDNF in human gliomas. Sichuan Da Xue Xue Bao Yi Xue Ban. 40:415–417. 2009.(In Chinese). PubMed/NCBI
45	Xiong J, Zhou L, Lim Y, Yang M, Zhu YH, Li ZW, Zhou FH, Xiao ZC and Zhou XF: Mature BDNF promotes the growth of glioma cells in vitro. Oncol Rep. 30:2719–2724. 2013. View Article : Google Scholar : PubMed/NCBI