microRNA‑214 suppresses the growth of cervical cancer cells by targeting EZH2

Yang,Yanling; Liu,Yang; Li,Guilin; Li,Lei; Geng,Peng; Song,Hongjuan

doi:10.3892/ol.2018.9363

microRNA‑214 suppresses the growth of cervical cancer cells by targeting EZH2

Authors:
- Yanling Yang
- Yang Liu
- Guilin Li
- Lei Li
- Peng Geng
- Hongjuan Song
View Affiliations

Affiliations: Department of Gynecology, Xuzhou Maternity and Child Health Care Hospital, Xuzhou, Jiangsu 221009, P.R. China
Published online on: August 24, 2018 https://doi.org/10.3892/ol.2018.9363
Pages: 5679-5686
Copyright: © Yang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

A number of studies have revealed the significance of microRNAs (miRs) in tumorigenesis. Cervical cancer (CC) is one of the most malignant cancer types and is associated with a poor overall survival rate. A previous study demonstrated a critical role of miR‑214 in the development of multiple cancer types, but its role in CC remains elusive. In the current study, miR‑214 was observed to be downregulated in CC tissues compared with the adjacent non‑cancerous tissue. Overexpression of miR‑214 reduced the proliferation of CC cells, whereas inhibiting its expression resulted in enhanced proliferation. Furthermore, Enhancer of zeste homolog 2 (EZH2) was demonstrated to be a direct target of miR‑214 in CC. An MTT assay demonstrated that upregulating miR‑214 expression or knocking down the expression of EZH2 impaired the proliferation of a CC cell line. Low expression of miR‑214 was positively associated with tumor differentiation (P=0.037) and tumor stage (P=0.012). Notably, low expression of miR‑214 predicted poor prognosis of patients with CC. Consequently, the results of the current study demonstrated that miR‑214 functions as a tumor suppressor in CC and may be regarded as a potential therapeutic target in CC.

View Figures

View References

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	Torre LA, Siegel RL, Ward EM and Jemal A: Global cancer incidence and mortality rates and trends-an update. Cancer Epidemiol Biomarkers Prev. 25:16–27. 2016. View Article : Google Scholar : PubMed/NCBI
3	Small W Jr, Bacon MA, Bajaj A, Chuang LT, Fisher BJ, Harkenrider MM, Jhingran A, Kitchener HC, Mileshkin LR, Viswanathan AN and Gaffney DK: Cervical cancer: A global health crisis. Cancer. 123:2404–2412. 2017. View Article : Google Scholar : PubMed/NCBI
4	Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, Jemal A, Yu XQ and He J: Cancer statistics in China, 2015. CA Cancer J Clin. 66:115–132. 2016. View Article : Google Scholar : PubMed/NCBI
5	Kent A: HPV vaccination and testing. Rev Obstet Gynecol. 3:33–34. 2010.PubMed/NCBI
6	Hildesheim A and Wang SS: Host and viral genetics and risk of cervical cancer: A review. Virus Res. 89:229–240. 2002. View Article : Google Scholar : PubMed/NCBI
7	Martin CM, Astbury K and O'Leary JJ: Molecular profiling of cervical neoplasia. Expert Rev Mol Diagn. 6:217–229. 2006. View Article : Google Scholar : PubMed/NCBI
8	Calin GA, Dumitru CD, Shimizu M, Bichi R, Zupo S, Noch E, Aldler H, Rattan S, Keating M, Rai K, et al: Frequent deletions and down-regulation of micro-RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia. Proc Natl Acad Sci USA. 99:pp. 15524–15529. 2002; View Article : Google Scholar : PubMed/NCBI
9	Ambros V: The functions of animal microRNAs. Nature. 431:350–355. 2004. View Article : Google Scholar : PubMed/NCBI
10	Liu Y, Hong W, Zhou C, Jiang Z, Wang G, Wei G and Li X: miR-539 inhibits FSCN1 expression and suppresses hepatocellular carcinoma migration and invasion. Oncol Rep. 37:2593–2602. 2017. View Article : Google Scholar : PubMed/NCBI
11	Chen Z, Wang M, He Q, Li Z, Zhao Y, Wang W, Ma J, Li Y and Chang G: MicroRNA-98 rescues proliferation and alleviates ox-LDL-induced apoptosis in HUVECs by targeting LOX-1. Exp Ther Med. 13:1702–1710. 2017. View Article : Google Scholar : PubMed/NCBI
12	Zhu Y, Wu G, Yan W, Zhan H and Sun P: miR-146b-5p regulates cell growth, invasion, and metabolism by targeting PDHB in colorectal cancer. Am J Cancer Res. 7:1136–1150. 2017.PubMed/NCBI
13	Liao J, Lin J, Lin D, Zou C, Kurata J, Lin R, He Z and Su Y: Down-regulation of miR-214 reverses erlotinib resistance in non-small-cell lung cancer through up-regulating LHX6 expression. Sci Rep. 7:7812017. View Article : Google Scholar : PubMed/NCBI
14	Liu B, Tian Y, Li F, Zhao Z, Jiang X, Zhao C, Han X and Zhang L: Tumor-suppressing roles of miR-214 and miR-218 in breast cancer. Oncol Rep. 35:3178–3184. 2016. View Article : Google Scholar : PubMed/NCBI
15	Yu G, Wang J, Xu K and Dong J: Dynamic regulation of uncoupling protein 2 expression by microRNA-214 in hepatocellular carcinoma. Biosci Rep. 36(pii): e003352016. View Article : Google Scholar : PubMed/NCBI
16	Lu Q, Xu L, Li C, Yuan Y, Huang S and Chen H: MiR-214 inhibits invasion and migration via downregulating GALNT7 in esophageal squamous cell cancer. Tumor Biol. 37:14605–14614. 2016. View Article : Google Scholar
17	Zhang Q and Zhang S: MiR-214 promotes radioresistance in human ovarian cancer cells by targeting PETN. Biosci Rep. 27:BSR201703272017. View Article : Google Scholar
18	Margueron R and Reinberg D: The Polycomb complex PRC2 and its mark in life. Nature. 469:343–349. 2011. View Article : Google Scholar : PubMed/NCBI
19	Di Croce L and Helin K: Transcriptional regulation by Polycomb group proteins. Nat Struct Mol Biol. 20:1147–1155. 2013. View Article : Google Scholar : PubMed/NCBI
20	Kleer CG, Cao Q, Varambally S, Shen R, Ota I, Tomlins SA, Ghosh D, Sewalt RG, Otte AP, Hayes DF, et al: EZH2 is a marker of aggressive breast cancer and promotes neoplastic transformation of breast epithelial cells. Proc Natl Acad Sci USA. 100:pp. 11606–11611. 2013; View Article : Google Scholar : PubMed/NCBI
21	Derfoul A, Juan AH, Difilippantonio MJ, Palanisamy N, Ried T and Sartorelli V: Decreased microRNA-214 levels in breast cancer cells coincides with increased cell proliferation, invasion and accumulation of the Polycomb Ezh2 methyltransferase. Carcinogenesis. 32:1607–1614. 2011. View Article : Google Scholar : PubMed/NCBI
22	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. 2011. View Article : Google Scholar
23	Yang LH, Yin SY, He RQ, Mo WJ, Pang YY, Wu YZ, Peng ZG and Gan TQ: Prospective target genes and pathways of miR-30a-5p in colorectal cancer: An investigation using TCGA and bioinformatics analysis. Int J Clin Exp Med. 10:4373–4385. 2017.
24	Zhang B, Pan X, Cobb GP and Anderson TA: MicroRNAs as oncogenes and tumor suppressors. Dev Biol. 302:1–12. 2017. View Article : Google Scholar
25	Yang Z, Chen S, Luan X, Li Y, Liu M, Li X, Liu T and Tang H: MicroRNA-214 is aberrantly expressed in cervical cancers and inhibits the growth of HeLa cells. IUBMB Life. 61:1075–1082. 2009. View Article : Google Scholar : PubMed/NCBI
26	Zhao X, Lu C, Chu W, Zhang Y, Zhang B, Zeng Q, Wang R, Li Z, Lv B and Liu J: microRNA-214 governs lung cancer growth and metastasis by targeting carboxypeptidase-D. DNA Cell Biol. 35:715–721. 2016. View Article : Google Scholar : PubMed/NCBI
27	Peng R, Men J, Ma R, Wang Q, Wang Y, Sun Y and Ren J: miR-214 down-regulates ARL2 and suppresses growth and invasion of cervical cancer cells. Biochem Biophys Res Commun. 484:623–630. 2017. View Article : Google Scholar : PubMed/NCBI
28	Wang JM, Ju BH, Pan CJ, Gu Y, Li MQ, Sun L, Xu YY and Yin LR: MiR-214 inhibits cell migration, invasion and promotes the drug sensitivity in human cervical cancer by targeting FOXM1. Am J Transl Res. 9:3541–3557. 2017.PubMed/NCBI
29	Chandrasekaran KS, Sathyanarayanan A and Karunagaran D: MicroRNA-214 suppresses growth, migration and invasion through a novel target, high mobility group AT-hook 1, in human cervical and colorectal cancer cells. Br J Cancer. 115:741–751. 2016. View Article : Google Scholar : PubMed/NCBI
30	Liu Y, Liu T, Bao X, He M, Li L and Yang X: Increased EZH2 expression is associated with proliferation and progression of cervical cancer and indicates a poor prognosis. Int J Gynecol Pathol. 33:218–224. 2014. View Article : Google Scholar : PubMed/NCBI
31	Juan AH, Kumar RM, Marx JG, Young RA and Sartorelli V: Mir-214-dependent regulation of the polycomb protein Ezh2 in skeletal muscle and embryonic stem cells. Mol Cell. 36:51–74. 2009. View Article : Google Scholar : PubMed/NCBI
32	Gao M, Liu Y, Chen Y, Yin C, Chen JJ and Liu S: miR-214 protects erythroid cells against oxidative stress by targeting ATF4 and EZH2. Free Radic Biol Med. 92:39–49. 2016. View Article : Google Scholar : PubMed/NCBI
33	Zhu WS, Tang CM, Xiao Z, Zhu JN, Lin QX, Fu YH, Hu ZQ, Zhang Z, Yang M, Zheng XL, et al: Targeting EZH1 and EZH2 contributes to the suppression of fibrosis-associated genes by miR-214-3p in cardiac myofibroblasts. Oncotarget. 7:78331–78342. 2016. View Article : Google Scholar : PubMed/NCBI
34	Yang T, Zhang GF, Chen XF, Gu HH, Fu SZ, Xu HF, Feng Q and Ni YM: MicroRNA-214 provokes cardiac hypertrophy via repression of EZH2. Biochem Biophys Res Commun. 436:578–584. 2013. View Article : Google Scholar : PubMed/NCBI
35	Xu C, He T, Li Z, Liu H and Ding B: Regulation of HOXA11-AS/miR-214-3p/EZH2 axis on the growth, migration and invasion of glioma cells. Biomed Pharmacother. 95:1504–1513. 2017. View Article : Google Scholar : PubMed/NCBI