microRNA‑200a functions as a tumor suppressor by targeting FOXA1 in glioma

Chen,Xiaofeng; Liu,Kun; Yang,Ping; Kuang,Weiping; Huang,Hongxing; Tu,Ewen; Li,Bo; Zhu,Yong; Zhou,Bin; Yan,Lin

doi:10.3892/etm.2018.6895

microRNA‑200a functions as a tumor suppressor by targeting FOXA1 in glioma

Authors:
- Xiaofeng Chen
- Kun Liu
- Ping Yang
- Weiping Kuang
- Hongxing Huang
- Ewen Tu
- Bo Li
- Yong Zhu
- Bin Zhou
- Lin Yan
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Affiliations: Department of Neurosurgery, Brain Hospital of Hunan Province, Changsha, Hunan 410007, P.R. China, Department of Psychiatry, Brain Hospital of Hunan Province, Changsha, Hunan 410007, P.R. China, Department of Neurology, Brain Hospital of Hunan Province, Changsha, Hunan 410007, P.R. China
Published online on: October 29, 2018 https://doi.org/10.3892/etm.2018.6895
Pages: 221-229
Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

microRNAs (miRs) serve primary roles in certain human malignancies; however, the detailed regulatory mechanism of miR‑200a in glioma progression is yet to be fully elucidated. The current study aimed to assess the expression of miR‑200a in glioma as well as the regulatory mechanism of miR‑200a in glioma cell proliferation, survival and invasion. RT‑qPCR and western blotting were performed to examine mRNA and protein expression. An MTT assay, an EdU incorporation cell proliferation assay and a transwell assay were utilized to assess cell survival, proliferation and invasion. The results indicated that the miR‑200a levels were significantly reduced in glioma tissues compared with normal brain tissues. Levels were also downregulated in glioma cell lines when compared with those in normal human astrocyte cells. Furthermore, low miR‑200a expression was associated with advanced progression of glioma. The overexpression of miR‑200a inhibited glioma cell proliferation, survival and invasion. Results also identified that FOXA1 was a target gene of miR‑200a in glioma cells and that the increased expression of FOXA1 was negatively correlated to the decreased expression of miR‑200a in glioma tissues. Furthermore, FOXA1 expression was negatively mediated by miR‑200a in glioma cells and the overexpression of FOXA1 eliminated the inhibitory effects of miR‑200a on the survival, proliferation and invasion of glioma cells. In conclusion, the current study demonstrated that miR‑200a functions acts as a tumor suppressor in glioma by directly targeting FOXA1 and may thus be a potential candidate for the treatment of glioma.

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1	Siegel RL, Miller KD and Jemal A: Cancer statistics, 2015. CA Cancer J Clin. 65:5–29. 2015. View Article : Google Scholar : PubMed/NCBI
2	Song H, Zhang Y, Liu N, Wan C, Zhang D, Zhao S, Kong Y and Yuan L: miR-92b regulates glioma cells proliferation, migration, invasion, and apoptosis via PTEN/Akt signaling pathway. J Physiol Biochem. 72:201–211. 2016. View Article : Google Scholar : PubMed/NCBI
3	Gu J, Xu R, Li Y, Zhang J and Wang S: MicroRNA-218 modulates activities of glioma cells by targeting HMGB1. Am J Transl Res. 8:3780–3790. 2016.PubMed/NCBI
4	Marumoto T and Saya H: Molecular biology of glioma. Adv Exp Med Biol. 746:2–11. 2012. View Article : Google Scholar : PubMed/NCBI
5	Ambros V: The functions of animal microRNAs. Nature. 431:350–355. 2004. View Article : Google Scholar : PubMed/NCBI
6	Ambros V: microRNAs: Tiny regulators with great potential. Cell. 107:823–826. 2001. View Article : Google Scholar : PubMed/NCBI
7	Zhou Y, Yang C, Wang K, Liu X and Liu Q: MicroRNA-33b inhibits the proliferation and migration of osteosarcoma cells via targeting hypoxia-inducible factor-1α. Oncol Res. 25:397–405. 2017. View Article : Google Scholar : PubMed/NCBI
8	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
9	Wang Y, Li J, Xu C and Zhang X: MicroRNA-139-5p inhibit cell proliferation and invasion by targeting RHO-associated Coiled-coil containing protein kinase 2 in ovarian cancer. Oncol Res. Jun 14–2017.(Epub ahead of print).
10	Wang C, Zhou B, Liu M, Liu Y and Gao R: miR-126-5p restoration promotes cell apoptosis in cervical cancer by targeting Bcl2l2. Oncol Res. 25:463–470. 2017. View Article : Google Scholar : PubMed/NCBI
11	Zhu Y, Zhao H, Rao M and Xu S: MicroRNA-365 inhibits proliferation, migration and invasion of glioma by targeting PIK3R3. Oncol Rep. 37:2185–2192. 2017. View Article : Google Scholar : PubMed/NCBI
12	Zhang T, Ma G, Zhang Y, Huo H and Zhao Y: miR-599 inhibits proliferation and invasion of glioma by targeting periostin. Biotechnol Lett. 39:1325–1333. 2017. View Article : Google Scholar : PubMed/NCBI
13	Li S, Zeng A, Hu Q, Yan W, Liu Y and You Y: miR-423-5p contributes to a malignant phenotype and temozolomide chemoresistance in glioblastomas. Neuro Oncol. 19:55–65. 2017. View Article : Google Scholar : PubMed/NCBI
14	Yoneyama K, Ishibashi O, Kawase R, Kurose K and Takeshita T: miR-200a, miR-200b and miR-429 are Onco-miRs that target the PTEN gene in endometrioid endometrial carcinoma. Anticancer Res. 35:1401–1410. 2015.PubMed/NCBI
15	Yang X, Wang J, Qu S, Zhang H, Ruan B, Gao Y, Ma B, Wang X, Wu N, Li X, et al: MicroRNA-200a suppresses metastatic potential of side population cells in human hepatocellular carcinoma by decreasing ZEB2. Oncotarget. 6:7918–7829. 2015.PubMed/NCBI
16	Yu SJ, Hu JY, Kuang XY, Luo JM, Hou YF, Di GH, Wu J, Shen ZZ, Song HY and Shao ZM: MicroRNA-200a promotes anoikis resistance and metastasis by targeting YAP1 in human breast cancer. Clin Cancer Res. 19:1389–1399. 2013. View Article : Google Scholar : PubMed/NCBI
17	Guo T, Zhang Y, Qu X, Che X, Li C, Fan Y, Wan X, Ma R, Hou K, Zhou H, et al: miR-200a enhances TRAIL-induced apoptosis in gastric cancer cells by targeting A20. Cell Biol Int. 42:506–514. 2018. View Article : Google Scholar : PubMed/NCBI
18	Zang Y, Tai Y, Wan B and Jia X: miR-200a-3p promotes the proliferation of human esophageal cancer cells by post-transcriptionally regulating cytoplasmic collapsin response mediator protein-1. Int J Mol Med. 38:1558–1564. 2016. View Article : Google Scholar : PubMed/NCBI
19	Peng F, Jiang J, Yu Y, Tian R, Guo X, Li X, Shen M, Xu M, Zhu F, Shi C, et al: Direct targeting of SUZ12/ROCK2 by miR-200b/c inhibits cholangiocarcinoma tumourigenesis and metastasis. Br J Cancer. 109:3092–3104. 2013. View Article : Google Scholar : PubMed/NCBI
20	Su Y, He Q, Deng L, Wang J, Liu Q, Wang D, Huang Q and Li G: MiR-200a impairs glioma cell growth, migration, and invasion by targeting SIM2-s. Neuroreport. 25:12–17. 2014.PubMed/NCBI
21	Qiu M, Bao W, Wang J, Yang T, He X, Liao Y and Wan X: FOXA1 promotes tumor cell proliferation through AR involving the Notch pathway in endometrial cancer. BMC Cancer. 14:782014. View Article : Google Scholar : PubMed/NCBI
22	Robinson JL and Carroll JS: FoxA1 is a key mediator of hormonal response in breast and prostate cancer. Front Endocrinol (Lausanne). 3:682012. View Article : Google Scholar : PubMed/NCBI
23	Guo W, Keener AL, Jing Y, Cai L, Ai J, Zhang J, Fisher AL, Fu G and Wang Z: FOXA1 modulates EAF2 regulation of AR transcriptional activity, cell proliferation, and migration in prostate cancer cells. Prostate. 75:976–987. 2015. View Article : Google Scholar : PubMed/NCBI
24	Horimoto Y, Arakawa A, Harada-Shoji N, Sonoue H, Yoshida Y, Himuro T, Igari F, Tokuda E, Mamat O, Tanabe M, et al: Low FOXA1 expression predicts good response to neo-adjuvant chemotherapy resulting in good outcomes for luminal HER2-negative breast cancer cases. Br J Cancer. 112:345–351. 2015. View Article : Google Scholar : PubMed/NCBI
25	Liu J, Chen B, Yue B and Yang J: MicroRNA-212 suppresses the proliferation and migration of osteosarcoma cells by targeting forkhead box protein A1. Exp Ther Med. 12:4135–4141. 2016. View Article : Google Scholar : PubMed/NCBI
26	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
27	Ma CC, Xiong Z, Zhu GN, Wang C, Zong G, Wang HL, Bian EB and Zhao B: Long non-coding RNA ATB promotes glioma malignancy by negatively regulating miR-200a. J Exp Clin Cancer Res. 35:902016. View Article : Google Scholar : PubMed/NCBI
28	Berthois Y, Delfino C, Metellus P, Fina F, Nanni-Metellus I, Al Aswy H, Pirisi V, Ouafik L and Boudouresque F: Differential expression of miR200a-3p and miR21 in grade II-III and grade IV gliomas: Evidence that miR200a-3p is regulated by O⁶-methylguanine methyltransferase and promotes temozolomide responsiveness. Cancer Biol Ther. 15:938–950. 2014. View Article : Google Scholar : PubMed/NCBI
29	Zheng L, Qian B, Tian D, Tang T, Wan S, Wang L, Zhu L and Geng X: FOXA1 positively regulates gene expression by changing gene methylation status in human breast cancer MCF-7 cells. Int J Clin Exp Pathol. 8:96–106. 2015.PubMed/NCBI
30	Wang L, Qin H, Li L, Feng F, Ji P, Zhang J, Li G, Zhao Z and Gao G: Forkhead-box A1 transcription factor is a novel adverse prognosis marker in human glioma. J Clin Neurosci. 20:654–658. 2013. View Article : Google Scholar : PubMed/NCBI