microRNA‑494 is a potential prognostic marker and inhibits cellular proliferation, migration and invasion by targeting SIRT1 in epithelial ovarian cancer

Yang,Aijun; Wang,Xuenan; Yu,Chunna; Jin,Zhenzhen; Wei,Lingxia; Cao,Jinghe; Wang,Qin; Zhang,Min; Zhang,Lin; Zhang,Lei; Hao,Cuifang

doi:10.3892/ol.2017.6501

microRNA‑494 is a potential prognostic marker and inhibits cellular proliferation, migration and invasion by targeting SIRT1 in epithelial ovarian cancer

Authors:
- Aijun Yang
- Xuenan Wang
- Chunna Yu
- Zhenzhen Jin
- Lingxia Wei
- Jinghe Cao
- Qin Wang
- Min Zhang
- Lin Zhang
- Lei Zhang
- Cuifang Hao
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Affiliations: Center for Reproductive Medicine, Affiliated Hospital of Jining Medical University, Jining, Shandong 272029, P.R. China, Department of Clinical Medicine, Jining Medical University, Jining, Shandong 272067, P.R. China, School of Life Science, Shandong Normal University, Jinan, Shandong 250014, P.R. China, Department of Gynecology and Obstetrics, Qing Dao University, Qingdao, Shandong 266071, P.R. China
Published online on: June 30, 2017 https://doi.org/10.3892/ol.2017.6501
Pages: 3177-3184

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Abstract

Ovarian cancer is one of the most common types of gynecological malignancy worldwide, and is the fourth leading cause of cancer‑associated mortality among women. Despite improvements in therapeutic treatments, the prognosis for epithelial ovarian cancer (EOC) remains poor, mainly due to the rapid growth and metastasis of ovarian cancer tumors. An increasing number of studies have indicated that microRNAs (miRNAs) are involved in the carcinogenesis and progression of human cancer, suggesting that miRNAs may be used in clinical prognosis and as a therapeutic target in EOC. The aim of the present study was to investigate the expression levels of miRNA‑494 in EOC tissues and cell lines. The clinical significance of miRNA‑494 in patients with EOC was also evaluated. The results demonstrated that miRNA‑494 was significantly downregulated in EOC tissues and cell lines. Low expression levels of miRNA‑494 were associated with poor prognostic features, including International Federation of Gynecology and Obstetrics stage, tumor size and lymph node metastasis. In vitro functional studies demonstrated that overexpression of miRNA‑494 inhibited proliferation, migration and invasion in EOC cells. By contrast, knockdown of miRNA‑494 enhanced cell growth, migration and invasion in EOC cells. Notably, sirtuin 1 (SIRT1) was identified as a direct target of miRNA‑494 in EOC. Furthermore, MTT, cell migration and invasion assays verified that EOC cell proliferation, migration and invasion were completely restored with forced miRNA‑494 expression and SIRT1 restoration. Together, these findings suggest that miRNA‑494 is a potential prognostic marker, and may provide novel therapeutic regimens of targeted therapy for EOC.

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1	Knutson KL, Karyampudi L, Lamichhane P and Preston C: Targeted immune therapy of ovarian cancer. Cancer Metastasis Rev. 34:53–74. 2015. View Article : Google Scholar : PubMed/NCBI
2	Siegel RL, Miller KD and Jemal A: Cancer statistics, 2015. CA Cancer J Clin. 65:5–29. 2015. View Article : Google Scholar : PubMed/NCBI
3	Suh DH, Kim JW, Kim K, Kim HJ and Lee KH: Major clinical research advances in gynecologic cancer in 2012. J Gynecol Oncol. 24:66–82. 2013. View Article : Google Scholar : PubMed/NCBI
4	Zhou Y, Wang M, Wu J, Jie Z, Chang S and Shuang T: The clinicopathological significance of miR-1307 in chemotherapy resistant epithelial ovarian cancer. J Ovarian Res. 8:232015. View Article : Google Scholar : PubMed/NCBI
5	Aletti GD, Gallenberg MM, Cliby WA, Jatoi A and Hartmann LC: Current management strategies for ovarian cancer. Mayo Clin Proc. 82:pp. 751–770. 2007; View Article : Google Scholar : PubMed/NCBI
6	Schwartz PE: Current diagnosis and treatment modalities for ovarian cancer. Cancer Treat Res. 107:99–118. 2002.PubMed/NCBI
7	Ji K, Ye L, Mason MD and Jiang WG: The Kiss-1/Kiss-1R complex as a negative regulator of cell motility and cancer metastasis (Review). Int J Mol Med. 32:747–754. 2013.PubMed/NCBI
8	Fan Y, Fan J, Huang L, Ye M, Huang Z, Wang Y, Li Q and Huang J: Increased expression of microRNA-196a predicts poor prognosis in human ovarian carcinoma. Int J Clin Exp Pathol. 8:4132–4137. 2015.PubMed/NCBI
9	Rutten MJ, van de Vrie R, Bruining A, Spijkerboer AM, Mol BW, Kenter GG and Buist MR: Predicting surgical outcome in patients with International Federation of Gynecology and Obstetrics stage III or IV ovarian cancer using computed tomography: A systematic review of prediction models. Int J Gynecol Cancer. 25:407–415. 2015. View Article : Google Scholar : PubMed/NCBI
10	Luo J, Zhou J, Cheng Q, Zhou C and Ding Z: Role of microRNA-133a in epithelial ovarian cancer pathogenesis and progression. Oncol Lett. 7:1043–1048. 2014.PubMed/NCBI
11	Katz B, Tropé CG, Reich R and Davidson B: MicroRNAs in Ovarian Cancer. Hum Pathol. 46:1245–1256. 2015. View Article : Google Scholar : PubMed/NCBI
12	Zhang S, Lu Z, Unruh AK, Ivan C, Baggerly KA, Calin GA, Li Z, Bast RC Jr and Le XF: Clinically relevant microRNAs in ovarian cancer. Mol Cancer Res. 13:393–401. 2015. View Article : Google Scholar : PubMed/NCBI
13	Lee RC, Feinbaum RL and Ambros V: The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell. 75:843–854. 1993. View Article : Google Scholar : PubMed/NCBI
14	Di Leva G and Croce CM: miRNA profiling of cancer. Curr Opin Genet Dev. 23:3–11. 2013. View Article : Google Scholar : PubMed/NCBI
15	Shah AA, Leidinger P, Blin N and Meese E: miRNA: Small molecules as potential novel biomarkers in cancer. Curr Med Chem. 17:4427–4432. 2010. View Article : Google Scholar : PubMed/NCBI
16	Jankovic R, Radulovic S and Brankovic-Magic M: siRNA and miRNA for the treatment of cancer. J BUON. 14 Suppl 1:S43–S49. 2009.PubMed/NCBI
17	Li X, Abdel-Mageed AB, Mondal D and Kandil E: MicroRNA expression profiles in differentiated thyroid cancer, a review. Int J Clin Exp Med. 6:74–80. 2013.PubMed/NCBI
18	Hwang HW and Mendell JT: MicroRNAs in cell proliferation, cell death, and tumorigenesis. Br J Cancer. 96 Suppl:R40–R44. 2007.PubMed/NCBI
19	Zhu W, Zhu D, Lu S, Wang T, Wang J, Jiang B, Shu Y and Liu P: miR-497 modulates multidrug resistance of human cancer cell lines by targeting BCL2. Med Oncol. 29:384–391. 2012. View Article : Google Scholar : PubMed/NCBI
20	Dong LL, Chen LM, Wang WM and Zhang LM: Decreased expression of microRNA-124 is an independent unfavorable prognostic factor for patients with breast cancer. Diagn Pathol. 10:452015. View Article : Google Scholar : PubMed/NCBI
21	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
22	Liu K, Liu S, Zhang W, Jia B, Tan L, Jin Z and Liu Y: miR-494 promotes cell proliferation, migration and invasion and increased sorafenib resistance in hepatocellular carcinoma by targeting PTEN. Oncol Rep. 34:1003–1010. 2015.PubMed/NCBI
23	Sun HB, Chen X, Ji H, Wu T, Lu HW, Zhang Y, Li H and Li YM: miR-494 is an independent prognostic factor and promotes cell migration and invasion in colorectal cancer by directly targeting PTEN. Int J Oncol. 45:2486–2494. 2014.PubMed/NCBI
24	Wang J, Chen H, Liao Y, Chen N, Liu T and Zhang H and Zhang H: Expression and clinical evidence of miR-494 and PTEN in non-small cell lung cancer. Tumour Biol. 36:6965–6972. 2015. View Article : Google Scholar : PubMed/NCBI
25	He W, Li Y, Chen X, Lu L, Tang B, Wang Z, Pan Y, Cai S, He Y and Ke Z: miR-494 acts as an anti-oncogene in gastric carcinoma by targeting c-myc. J Gastroenterol Hepatol. 29:1427–1434. 2014. View Article : Google Scholar : PubMed/NCBI
26	Shen PF, Chen XQ, Liao YC, Chen N, Zhou Q, Wei Q, Li X, Wang J and Zeng H: MicroRNA-494-3p targets CXCR4 to suppress the proliferation, invasion, and migration of prostate cancer. Prostate. 74:756–767. 2014. View Article : Google Scholar : PubMed/NCBI
27	Zhang R, Chen X, Zhang S, Zhang X, Li T, Liu Z, Wang J, Zang W, Wang Y, Du Y and Zhao G: Upregulation of miR-494 inhibits cell growth and invasion and induces cell apoptosis by targeting cleft lip and palate transmembrane 1-like in esophageal squamous cell carcinoma. Dig Dis Sci. 60:1247–1255. 2015. View Article : Google Scholar : PubMed/NCBI
28	Liborio-Kimura TN, Jung HM and Chan EK: miR-494 represses HOXA10 expression and inhibits cell proliferation in oral cancer. Oral Oncol. 51:151–157. 2015. View Article : Google Scholar : PubMed/NCBI
29	Song L, Liu D, Wang B, He J, Zhang S, Dai Z, Ma X and Wang X: miR-494 suppresses the progression of breast cancer in vitro by targeting CXCR4 through the Wnt/β-catenin signaling pathway. Oncol Rep. 34:525–531. 2015.PubMed/NCBI
30	Liu Y, Li X, Zhu S, Zhang JG, Yang M, Qin Q, Deng SC, Wang B, Tian K, Liu L, et al: Ectopic expression of miR-494 inhibited the proliferation, invasion and chemoresistance of pancreatic cancer by regulating SIRT1 and c-Myc. Gene Ther. 22:729–738. 2015. View Article : Google Scholar : PubMed/NCBI
31	Li J, Wang L, Liu Z, Zu C, Xing F, Yang P, Yang Y, Dang X and Wang K: MicroRNA-494 inhibits cell proliferation and invasion of chondrosarcoma cells in vivo and in vitro by directly targeting SOX9. Oncotarget. 6:26216–26229. 2015. View Article : Google Scholar : PubMed/NCBI
32	Chen B, Hou Z, Li C and Tong Y: MiRNA-494 inhibits metastasis of cervical cancer through Pttg1. Tumour Biol. 36:7143–7149. 2015. View Article : Google Scholar : PubMed/NCBI
33	Guarente L and Picard F: Calorie restriction-the SIR2 connection. Cell. 120:473–482. 2005. View Article : Google Scholar : PubMed/NCBI
34	Blander G and Guarente L: The Sir2 family of protein deacetylases. Annu Rev Biochem. 73:417–435. 2004. View Article : Google Scholar : PubMed/NCBI
35	Hida Y, Kubo Y, Murao K and Arase S: Strong expression of a longevity-related protein, SIRT1, in Bowen's disease. Arch Dermatol Res. 299:103–106. 2007. View Article : Google Scholar : PubMed/NCBI
36	Huffman DM, Grizzle WE, Bamman MM, Kim JS, Eltoum IA, Elgavish A and Nagy TR: SIRT1 is significantly elevated in mouse and human prostate cancer. Cancer Res. 67:6612–6618. 2007. View Article : Google Scholar : PubMed/NCBI
37	Kuzmichev A, Margueron R, Vaquero A, Preissner TS, Scher M, Kirmizis A, Ouyang X, Brockdorff N, Abate-Shen C, Farnham P and Reinberg D: Composition and histone substrates of polycomb repressive group complexes change during cellular differentiation. Proc Natl Acad Sci USA. 102:pp. 1859–1864. 2005; View Article : Google Scholar : PubMed/NCBI
38	Chen WY, Wang DH, Yen RC, Luo J, Gu W and Baylin SB: Tumor suppressor HIC1 directly regulates SIRT1 to modulate p53-dependent DNA-damage responses. Cell. 123:437–448. 2005. View Article : Google Scholar : PubMed/NCBI
39	Yamakuchi M, Ferlito M and Lowenstein CJ: miR-34a repression of SIRT1 regulates apoptosis. Proc Natl Acad Sci USA. 105:pp. 13421–13426. 2008; View Article : Google Scholar : PubMed/NCBI
40	Lai L, Yan L, Gao S, Hu CL, Ge H, Davidow A, Park M, Bravo C, Iwatsubo K, Ishikawa Y, et al: Type 5 adenylyl cyclase increases oxidative stress by transcriptional regulation of manganese superoxide dismutase via the SIRT1/FoxO3a pathway. Circulation. 127:1692–1701. 2013. View Article : Google Scholar : PubMed/NCBI
41	Mouchiroud L, Houtkooper RH, Moullan N, Katsyuba E, Ryu D, Cantó C, Mottis A, Jo YS, Viswanathan M, Schoonjans K, et al: The NAD(+)/sirtuin pathway modulates longevity through activation of mitochondrial UPR and FOXO signaling. Cell. 154:430–441. 2013. View Article : Google Scholar : PubMed/NCBI
42	Zhang Y, Zhang M, Dong H, Yong S, Li X, Olashaw N, Kruk PA, Cheng JQ, Bai W, Chen J, et al: Deacetylation of cortactin by SIRT1 promotes cell migration. Oncogene. 28:445–460. 2009. View Article : Google Scholar : PubMed/NCBI
43	Jang KY, Kim KS, Hwang SH, Kwon KS, Kim KR, Park HS, Park BH, Chung MJ, Kang MJ, Lee DG and Moon WS: Expression and prognostic significance of SIRT1 in ovarian epithelial tumours. Pathology. 41:366–371. 2009. View Article : Google Scholar : PubMed/NCBI
44	Mvunta DH, Miyamoto T, Asaka R, Yamada Y, Ando H, Higuchi S, Ida K, Kashima H and Shiozawa T: Overexpression of SIRT1 is associated with poor outcomes in patients with ovarian carcinoma. Appl Immunohistochem Mol Morphol. Feb 9–2016.(Epub ahead of print).
45	Shi Y, Huang J, Zhou J, Liu Y, Fu X, Li Y, Yin G and Wen J: MicroRNA-204 inhibits proliferation, migration, invasion and epithelial-mesenchymal transition in osteosarcoma cells via targeting Sirtuin 1. Oncol Rep. 34:399–406. 2015.PubMed/NCBI
46	Li K, Xyu Q, Liu X, Liu Q and Wang M: Growth inhibition of human hepatocellular carcinoma by miRNA-204 via down-regulation of Bcl-2 and Sirt1 expression. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 31:168–172. 2015.(In Chinese). PubMed/NCBI
47	Yamakuchi M: MicroRNA regulation of SIRT1. Front Physiol. 3:682012. View Article : Google Scholar : PubMed/NCBI