miR-34c plays a role of tumor suppressor in HEC‑1-B cells by targeting E2F3 protein

Li,Fuyao; Chen,Huijun; Huang,Yibo; Zhang,Qian; Xue,Jisen; Liu,Zan; Zheng,Feiyun

doi:10.3892/or.2015.3894

miR-34c plays a role of tumor suppressor in HEC‑1-B cells by targeting E2F3 protein

Authors:
- Fuyao Li
- Huijun Chen
- Yibo Huang
- Qian Zhang
- Jisen Xue
- Zan Liu
- Feiyun Zheng
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Affiliations: Department of Gynecology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China, Department of General Surgery, Zhuzhou Kind Hospital, Zhuzhou, Hunan 412000, P.R. China
Published online on: April 2, 2015 https://doi.org/10.3892/or.2015.3894
Pages: 3069-3074

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Abstract

Endometrial carcinoma (EC) is a common malignancy of the female genital tract with a poor prognosis. It has been reported that miR-34c is significantly reduced in EC, but research concerning its function in EC is rare. In the present study, the expression of miR-34c was upregulated in the EC cell line, HEC-1-B, by transfecting the cells with hsa-miR-34c-5p mimics. Then, after determining the transfection efficiency by RT-qPCR, we analyzed the effects of miR-34c on the HEC-1-B cells. We found that overexpression of miR-34c significantly inhibited cell proliferation, colony formation, migration and invasion and induced cell cycle arrest and apoptosis. Finally, western blot analysis demonstrated that the expression of E2F3 was reduced after upregulation of the expression of miR-34c in the HEC-1-B cells, and the effects of miR-34c are likely associated with the reduction in E2F3 protein. In conclusion, our study demonstrated that miR-34c plays a role of tumor suppressor in HEC-1-B cells, and E2F3 protein may be a target of miR-34c.

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1	Ueda SM, Kapp DS, Cheung MK, Shin JY, Osann K, Husain A, Teng NN, Berek JS and Chan JK: Trends in demographic and clinical characteristics in women diagnosed with corpus cancer and their potential impact on the increasing number of deaths. Am J Obstet Gynecol. 198:218.e1–218.e6. 2008. View Article : Google Scholar
2	Bartel DP: MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 116:281–297. 2004. View Article : Google Scholar : PubMed/NCBI
3	Takamizawa J, Konishi H, Yanagisawa K, Tomida S, Osada H, Endoh H, Harano T, Yatabe Y, Nagino M, Nimura Y, et al: Reduced expression of the let-7 microRNAs in human lung cancers in association with shortened postoperative survival. Cancer Res. 64:3753–3756. 2004. View Article : Google Scholar : PubMed/NCBI
4	Bou Kheir T, Futoma-Kazmierczak E, Jacobsen A, Krogh A, Bardram L, Hother C, Grønbæk K, Federspiel B, Lund AH and Friis-Hansen L: miR-449 inhibits cell proliferation and is down-regulated in gastric cancer. Mol Cancer. 10:292011. View Article : Google Scholar : PubMed/NCBI
5	Esquela-Kerscher A and Slack FJ: Oncomirs - microRNAs with a role in cancer. Nat Rev Cancer. 6:259–269. 2006. View Article : Google Scholar : PubMed/NCBI
6	Jiang F, Liu T, He Y, Yan Q, Chen X, Wang H and Wan X: MiR-125b promotes proliferation and migration of type II endometrial carcinoma cells through targeting TP53INP1 tumor suppressor in vitro and in vivo. BMC Cancer. 11:4252011. View Article : Google Scholar : PubMed/NCBI
7	Tsuruta T, Kozaki K, Uesugi A, Furuta M, Hirasawa A, Imoto I, Susumu N, Aoki D and Inazawa J: miR-152 is a tumor suppressor microRNA that is silenced by DNA hypermethylation in endometrial cancer. Cancer Res. 71:6450–6462. 2011. View Article : Google Scholar : PubMed/NCBI
8	Le XF, Merchant O, Bast RC and Calin GA: The roles of microRNAs in the cancer invasion-metastasis cascade. Cancer Microenviron. 3:137–147. 2010. View Article : Google Scholar
9	Ye W, Xue J, Zhang Q, Li F, Zhang W, Chen H, Huang Y and Zheng F: miR-449a functions as a tumor suppressor in endometrial cancer by targeting CDC25A. Oncol Rep. 32:1193–1199. 2014.PubMed/NCBI
10	Wong MY, Yu Y, Walsh WR and Yang JL: microRNA-34 family and treatment of cancers with mutant or wild-type p53 (Review). Int J Oncol. 38:1189–1195. 2011.PubMed/NCBI
11	Son MS, Jang MJ, Jeon YJ, Kim WH, Kwon CI, Ko KH, Park PW, Hong SP, Rim KS, Kwon SW, et al: Promoter polymorphisms of pri-miR-34b/c are associated with hepatocellular carcinoma. Gene. 524:156–160. 2013. View Article : Google Scholar : PubMed/NCBI
12	Roy S, Levi E, Majumdar AP and Sarkar FH: Expression of miR-34 is lost in colon cancer which can be re-expressed by a novel agent CDF. J Hematol Oncol. 5:582012. View Article : Google Scholar : PubMed/NCBI
13	Oeggerli M, Tomovska S, Schraml P, Calvano-Forte D, Schafroth S, Simon R, Gasser T, Mihatsch MJ and Sauter G: E2F3 amplification and overexpression is associated with invasive tumor growth and rapid tumor cell proliferation in urinary bladder cancer. Oncogene. 23:5616–5623. 2004. View Article : Google Scholar : PubMed/NCBI
14	Ziebold U, Reza T, Caron A and Lees JA: E2F3 contributes both to the inappropriate proliferation and to the apoptosis arising in Rb mutant embryos. Genes Dev. 15:386–391. 2001. View Article : Google Scholar : PubMed/NCBI
15	Hiroki E, Suzuki F, Akahira J, Nagase S, Ito K, Sugawara J, Miki Y, Suzuki T, Sasano H and Yaegashi N: MicroRNA-34b functions as a potential tumor suppressor in endometrial serous adenocarcinoma. Int J Cancer. 131:E395–E404. 2012. View Article : Google Scholar
16	Jiang L, Meng W, Zeng J, Hu H and Lu L: MiR-34c oligonucleotide enhances chemosensitivity of Ishikawa cell to cisplatin by inducing apoptosis. Cell Biol Int. 37:577–583. 2013. View Article : Google Scholar : PubMed/NCBI
17	Kubo T, Toyooka S, Tsukuda K, Sakaguchi M, Fukazawa T, Soh J, Asano H, Ueno T, Muraoka T, Yamamoto H, et al: Epigenetic silencing of microRNA-34b/c plays an important role in the pathogenesis of malignant pleural mesothelioma. Clin Cancer Res. 17:4965–4974. 2011. View Article : Google Scholar : PubMed/NCBI
18	Toyota M, Suzuki H, Sasaki Y, Maruyama R, Imai K, Shinomura Y and Tokino T: Epigenetic silencing of microRNA-34b/c and B-cell translocation gene 4 is associated with CpG island methylation in colorectal cancer. Cancer Res. 68:4123–4132. 2008. View Article : Google Scholar : PubMed/NCBI
19	He L, He X, Lim LP, de Stanchina E, Xuan Z, Liang Y, Xue W, Zender L, Magnus J, Ridzon D, et al: A microRNA component of the p53 tumour suppressor network. Nature. 447:1130–1134. 2007. View Article : Google Scholar : PubMed/NCBI
20	Chen HZ, Tsai SY and Leone G: Emerging roles of E2Fs in cancer: an exit from cell cycle control. Nat Rev Cancer. 9:785–797. 2009. View Article : Google Scholar : PubMed/NCBI
21	Timmers C, Sharma N, Opavsky R, Maiti B, Wu L, Wu J, Orringer D, Trikha P, Saavedra HI and Leone G: E2f1, E2f2, and E2f3 control E2F target expression and cellular proliferation via a p53-dependent negative feedback loop. Mol Cell Biol. 27:65–78. 2007. View Article : Google Scholar :
22	Lax SF, Kendall B, Tashiro H, Slebos RJ and Hedrick L: The frequency of p53, K-ras mutations, and microsatellite instability differs in uterine endometrioid and serous carcinoma: evidence of distinct molecular genetic pathways. Cancer. 88:814–824. 2000. View Article : Google Scholar : PubMed/NCBI
23	Corney DC, Flesken-Nikitin A, Godwin AK, Wang W and Nikitin AY: MicroRNA-34b and microRNA-34c are targets of p53 and cooperate in control of cell proliferation and adhesion-independent growth. Cancer Res. 67:8433–8438. 2007. View Article : Google Scholar : PubMed/NCBI
24	Foster CS, Falconer A, Dodson AR, Norman AR, Dennis N, Fletcher A, Southgate C, Dowe A, Dearnaley D, Jhavar S, et al: Transcription factor E2F3 overexpressed in prostate cancer independently predicts clinical outcome. Oncogene. 23:5871–5879. 2004. View Article : Google Scholar : PubMed/NCBI
25	Leone G, DeGregori J, Yan Z, Jakoi L, Ishida S, Williams RS and Nevins JR: E2F3 activity is regulated during the cell cycle and is required for the induction of S phase. Genes Dev. 12:2120–2130. 1998. View Article : Google Scholar : PubMed/NCBI
26	Migliore C, Petrelli A, Ghiso E, Corso S, Capparuccia L, Eramo A, Comoglio PM and Giordano S: MicroRNAs impair MET-mediated invasive growth. Cancer Res. 68:10128–10136. 2008. View Article : Google Scholar : PubMed/NCBI
27	Li Z, Gou J and Xu J: Down-regulation of focal adhesion signaling in response to cyclophilin A knockdown in human endometrial cancer cells, implicated by cDNA microarray analysis. Gynecol Oncol. 131:191–197. 2013. View Article : Google Scholar : PubMed/NCBI