MicroRNA‑10a‑5p suppresses cancer proliferation and division in human cervical cancer by targeting BDNF

Zhai,Liancheng; Li,Yanli; Lan,Xinzhi; Ai,Liang

doi:10.3892/etm.2017.5312

MicroRNA‑10a‑5p suppresses cancer proliferation and division in human cervical cancer by targeting BDNF

Authors:
- Liancheng Zhai
- Yanli Li
- Xinzhi Lan
- Liang Ai
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Affiliations: Laboratory Department, Maternal and Child Health Care Hospital of Zhengzhou, Zhengzhou, Henan 450000, P.R. China
Published online on: October 16, 2017 https://doi.org/10.3892/etm.2017.5312
Pages: 6147-6151

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Abstract

The aim of the present study was to investigate the effect and mechanism of microRNA (miR)‑10a‑5p in human cervical cancer. The expression level of miR‑10‑5p in cervical cancer lines was assessed using reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR). In cervical cancer HeLa and SiHa cells, miR‑10‑5p was ectopically overexpressed by lentiviral transduction. Brain‑derived neurotrophic factor (BDNF) was then overexpressed in HeLa and SiHa cells to evaluate its selective effect on miR‑10‑5p in cervical cancer modulation. The targeting of miR‑10‑5p on its downstream gene, BDNF, was evaluated using RT‑qPCR and western blot analysis. Cervical cancer cell viability and cell cycle was evaluated using an MTT assay and flow cytometry, respectively. The results indicated that miR‑10‑5p expression was significantly lower in cervical cancer cell lines compared with normal cells (P<0.05). Ectopic overexpression of miR‑10‑5p significantly inhibited cancer cell viability and induced cell cycle arrest in HeLa and SiHa cells (both P<0.05). miR‑10‑5p overexpression significantly reduced BDNF gene expression (P<0.05) and also reduced BDNF protein levels in cervical cancer cells compared with the control. In conclusion, the current study indicated that miR‑10‑5p is a cervical cancer suppressor, which regulates BDNF expression in cervical cancer.

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1	Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J and Jemal A: Global cancer statistics, 2012. CA Cancer J Clin. 65:87–108. 2015. View Article : Google Scholar : PubMed/NCBI
2	Nam EJ, Kim JW, Hong JW, Jang HS, Lee SY, Jang SY, Lee DW, Kim SW, Kim JH, Kim YT, et al: Expression of the p16INK-4a and Ki-67 in relation to the grade of cervical intraepithelial neoplasia and high-risk human papillomavirus infection. J Gynecol Oncol. 19:162–168. 2008. View Article : Google Scholar : PubMed/NCBI
3	Oluwole OP, Okoyomo OO, Onile TG, Alabi OO and Gbejegbe JO: Cervical carcinoma, still a burden: Histopathological analysis and review on the literature. Adv Lab Med Int. 6:1–6. 2016.
4	Laukkanen P, Läärä E, Koskela P, Pukkala E, Virkkunen H and Lehtinen M: Population fraction of cervical neoplasia attributable to high-risk human papillomaviruses. Future Oncol. 6:709–716. 2010. View Article : Google Scholar : PubMed/NCBI
5	Nilsen TW: Mechanisms of microRNA-mediated gene regulation in animal cells. Trends Genet. 23:243–249. 2007. View Article : Google Scholar : PubMed/NCBI
6	Zhang B, Pan X, Cobb GP and Anderson TA: MicroRNAs as oncogenes and tumor suppression. Dev Biol. 302:1–12. 2007. View Article : Google Scholar : PubMed/NCBI
7	Liu F, Zhang S, Zhao Z, Mao X, Huang J, Wu Z, Zheng L and Wang Q: MicroRNA-27b up-regulated by human papillomavirus 16 E7 promotes proliferation and suppresses apoptosis by targeting polo-like kinase2 in cervical cancer. Oncogarget. 7:19666–19679. 2016. View Article : Google Scholar
8	Wang WT, Zhao YN, Yan JX, Weng MY, Wang Y, Chen YQ and Hong SJ: Differentially expressed microRNAs in the serum of cervical squamous cell carcinoma patients before and after surgery. J Hematol Oncol. 7:62014. View Article : Google Scholar : PubMed/NCBI
9	Ma Q, Wan G, Wang S, Yang W, Zhang J and Yao X: Serum of microRNA-205 as a novel biomarker for cervical cancer patients. Cancer Cell Int. 14:812014. View Article : Google Scholar : PubMed/NCBI
10	Mi Y, Wang L, Zong L, Pei M, Lu Q and Huang P: Genetic variants in microRNA target sites of 37 selected cancer-related genes and the risk of cervical cancer. PLoS One. 9:e860612014. View Article : Google Scholar : PubMed/NCBI
11	Safan A, Seifolesiami M, Yahaghi E, Sedaghati F and Khameneie MK: Retracted Article: Upregulation of miR-20a and miR-10a expression levels act as potential biomarkers of aggressive progression and poor prognosis in cervical cancer. Tumour Biol. Oct 1–2015.(Epub ahead of print).
12	Zhang L, Sun J, Wang B, Ren JC, Su W and Zhang T: MicroRNA-10b triggers the epithelial-mesenchymal transition (EMT) of laryngeal carcinoma Hep-2 cells by directly targeting the E-cadherin. Appl Biochem Biotechnol. 176:33–44. 2015. View Article : Google Scholar : PubMed/NCBI
13	McAllister AK: Neurotrophins and neuronal differentiation in the central nervous system. Cell Mol Life Sci. 58:1054–1060. 2001. View Article : Google Scholar : PubMed/NCBI
14	Cao L, Liu X, Lin EJ, Wang C, Choi EY, Riban V, Lin B and During MJ: Environmental and genetic activation of a brain-adipocyte BDNF/leptin axis causes cancer remission and inhibition. Cell. 142:52–64. 2010. View Article : Google Scholar : PubMed/NCBI
15	Kaplan DR, Matsumoto K, Lucarelli E and Thiele CJ: Induction of TrkB by retinoic acid mediates biologic responsiveness to BDNF and differentiation of human neuroblastoma cells. Eukaryotic Signal Transduction Group. Neuron. 11:321–331. 1993. View Article : Google Scholar : PubMed/NCBI
16	Hu Z, Shen WJ, Kraemer FB and Azhar S: MicroRNAs 125a and 455 repress lipoprotein-supported steroidogenesis by targeting scavenger receptor class B type I in steroidogenic cells. Mol Cell Biol. 32:5035–5045. 2012. View Article : Google Scholar : PubMed/NCBI
17	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
18	Guo D, Hou X, Zhang H, Sun W, Zhu L, Liang J and Jiang X: More expressions of BDNF and TrkB in multiple hepatocellular carcinoma and anti-BDNF or K252a induced apoptosis, supressed invasion of HepG2 and HCCLM3 cells. J Exp Clin Cancer Res. 30:972011. View Article : Google Scholar : PubMed/NCBI
19	Müller S: In silico analysis of regulatory networks underlined the role of miR-10b-5p and its target BDNF in huntington's disease. Transl Neurodegener. 3:172014. View Article : Google Scholar : PubMed/NCBI
20	Du X, Lin LI, Zhang L and Jiang J: microRNA-195 inhibits the proliferation, migration and invasion of cervical cancer cells via the inhibition of CCND2 and MYB expression. Oncol Lett. 10:2639–2643. 2015.PubMed/NCBI
21	Hu Y and Liu H: MicroRNA-10a-5p and microRNA-34c-5p in laryngeal epithelial premalignant lesions: Differential expression and clinicopathological correlation. Eur Arch Otorhinolaryngol. 272:391–399. 2015. View Article : Google Scholar : PubMed/NCBI
22	Wang X, Ling CC, Li L, Qin Y, Qi J, Liu X, You B, Shi Y, Zhang J, Jiang Q, et al: MicroRNA-10a/10b represses a novel target gene mib1 to regulate angiogenesis. Carrdiovasc Res. 110:140–150. 2016. View Article : Google Scholar
23	Stadthagen G, Tehler D, Høyland-Kroghsbo NM, Wen J, Krogh A, Jensen KT, Santoni-Rugiu E, Engelholm LH and Lund AH: Loss of miR-10a activates lpo and collaborates with activated Wnt signaling in inducing intestinal neoplasia in female mice. PLoS Genet. 9:e10039132013. View Article : Google Scholar : PubMed/NCBI
24	Liu X, McMruphy T, Xiao R, Slater A, Huang W and Cao L: Hypothalamic gene transfer of BDNF inhibits breast cancer progression and metastasis in middle age obese mice. Mol Ther. 22:1275–1284. 2014. View Article : Google Scholar : PubMed/NCBI