MicroRNA‑665 suppresses the growth and migration of ovarian cancer cells by targeting HOXA10

Liu,Jinhui; Jiang,Yi; Wan,Yicong; Zhou,Shulin; Thapa,Sunita; Cheng,Wenjun

doi:10.3892/mmr.2018.9252

MicroRNA‑665 suppresses the growth and migration of ovarian cancer cells by targeting HOXA10

Authors:
- Jinhui Liu
- Yi Jiang
- Yicong Wan
- Shulin Zhou
- Sunita Thapa
- Wenjun Cheng
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Affiliations: Department of Gynecology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China
Published online on: July 5, 2018 https://doi.org/10.3892/mmr.2018.9252
Pages: 2661-2668
Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Ovarian cancer is the most lethal gynecological cancer and its metastasis leads to a poor prognosis. The present study was designed to elucidate how microRNA (miR)‑665 regulates the proliferation and migration of ovarian tumor cells. Reverse transcription‑polymerase chain reaction (RT‑PCR) demonstrated that miR‑665 expression was decreased in ovarian cancer tissues. Increased expression of miR‑665 suppressed the growth and migration of ovarian cancer cells, whereas the downregulated expression of miR‑665 led to the opposite results. Bioinformatics tools identified homeobox A10 (HOXA10) as a target of miR‑665. Following miR‑665 overexpression, HOXA10 protein expression was significantly reduced. A dual luciferase assay revealed that miR‑665 bound to the 3'‑untranslated region of HOXA10. Immunohistochemistry and RT‑PCR revealed that the expression of HOXA10 was negatively correlated with the expression of miR‑665. It was concluded that miR‑665 targets HOXA10 and may act as a tumor‑suppressing gene in ovarian cancer. This pathway may be involved in the development and metastasis of ovarian cancer.

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1	Xian H, Xian Y, Liu L, Wang Y, He J and Huang J: Expression of β-nerve growth factor and homeobox A10 in experimental cryptorchidism treated with exogenous nerve growth factor. Mol Med Rep. 11:2875–2881. 2015. View Article : Google Scholar : PubMed/NCBI
2	Guo R, Sherman-Baust C and Abdelmohsen K: miRNA-based ovarian cancer diagnosis and therapySarkar F: microRNA Targeted Cancer Therapy. Springer; Cham: pp. 115–127. 2014, View Article : Google Scholar
3	Bartel DP: MicroRNAs: Genomics, biogenesis, mechanism, and function. Cell. 116:281–297. 2004. View Article : Google Scholar : PubMed/NCBI
4	Hornstein E, Mansfield JH, Yekta S, Hu JK, Harfe BD, McManus MT, Baskerville S, Bartel DP and Tabin CJ: The microRNA miR-196 acts upstream of Hoxb8 and Shh in limb development. Nature. 438:671–674. 2005. View Article : Google Scholar : PubMed/NCBI
5	Boehm M and Slack FJ: microRNA control of lifespan and metabolism. Cell Cycle. 5:837–840. 2006. View Article : Google Scholar : PubMed/NCBI
6	Tang W, Jiang Y, Mu X, Xu L, Cheng W and Wang X: MiR-135a functions as a tumor suppressor in epithelial ovarian cancer and regulates HOXA10 expression. Cell Signal. 26:1420–1426. 2014. View Article : Google Scholar : PubMed/NCBI
7	Wang F, Chang TH, Kao CJ and Huang RS: High expression of miR-532-5p, a tumor suppressor, leads to better prognosis in ovarian cancer both in vivo and in vitro. Mol Cancer Ther. 15:1123–1131. 2016. View Article : Google Scholar : PubMed/NCBI
8	Zhao H, Yu X, Ding Y, Zhao J, Wang G, Wu X, Jiang J, Peng C, Guo GZ and Cui S: MiR-770-5p inhibits cisplatin chemoresistance in human ovarian cancer by targeting ERCC2. Oncotarget. 7:53254–53268. 2016.PubMed/NCBI
9	Zhao X, Zhou Y, Chen YU and Yu F: miR-494 inhibits ovarian cancer cell proliferation and promotes apoptosis by targeting FGFR2. Oncol Lett. 11:4245–4251. 2016. View Article : Google Scholar : PubMed/NCBI
10	Hu K and Liang M: Upregulated microRNA-224 promotes ovarian cancer cell proliferation by targeting KLLN. In Vitro Cell Dev Biol Anim. 53:149–156. 2017. View Article : Google Scholar : PubMed/NCBI
11	Xiaohong Z, Lichun F, Na X, Kejian Z, Xiaolan X and Shaosheng W: MiR-203 promotes the growth and migration of ovarian cancer cells by enhancing glycolytic pathway. Tumour Biol. 37:14989–14997. 2016. View Article : Google Scholar : PubMed/NCBI
12	Chen S, Chen X, Xiu YL, Sun KX and Zhao Y: MicroRNA-490-3P targets CDK1 and inhibits ovarian epithelial carcinoma tumorigenesis and progression. Cancer Lett. 362:122–130. 2015. View Article : Google Scholar : PubMed/NCBI
13	Zheng HB, Zheng XG and Liu BP: miRNA-101 inhibits ovarian cancer cells proliferation and invasion by down-regulating expression of SOCS-2. Int J Clin Exp Med. 8:20263–20270. 2015.PubMed/NCBI
14	Zang W, Wang Y, Du Y, Xuan X, Wang T, Li M, Ma Y, Li P, Chen X, Dong Z and Zhao G: Differential expression profiling of microRNAs and their potential involvement in esophageal squamous cell carcinoma. Tumor Biol. 35:3295–3304. 2014. View Article : Google Scholar
15	Cheng W, Gao JP, Zhang ZG, Jing-Ping GE, Feng XU and Wei ZF: Study on microRNAs in urothelial carcinoma(II grade) of the bladder. J Med Postgrad. 23:48–52. 2010.
16	Chen J, Sun D, Chu H, Gong Z, Zhang C, Gong B, Li Y, Li N and Jiang L: Screening of differential microRNA expression in gastric signet ring cell carcinoma and gastric adenocarcinoma and target gene prediction. Oncol Rep. 33:2963–2971. 2015. View Article : Google Scholar : PubMed/NCBI
17	Hatanaka Y, De Velasco MA, Kura Y, Yamamoto Y, Kodama M, Nozawa M, Shimizu N, Yoshimura K, Yoshikawa K, Nishio K and Uemura H: Abstract 3629: HOXA10 expression profiles in prostate cancer. Cancer Res. 72 8 Suppl:S36292012. View Article : Google Scholar
18	Thorsteinsdottir U, Sauvageau G, Hough MR, Dragowska W, Lansdorp PM, Lawrence HJ, Largman C and Humphries RK: Overexpression of HOXA10 in murine hematopoietic cells perturbs both myeloid and lymphoid differentiation and leads to acute myeloid leukemia. Mol Cell Biol. 17:495–505. 1997. View Article : Google Scholar : PubMed/NCBI
19	Chu MC, Selam FB and Taylor HS: HOXA10 regulates p53 expression and matrigel invasion in human breast cancer cells. Cancer Biol Ther. 3:568–572. 2004. View Article : Google Scholar : PubMed/NCBI
20	Chen Y, Zhang J, Wang H, Zhao J, Xu C, Du Y, Luo X, Zheng F, Liu R, Zhang H and Ma D: miRNA-135a promotes breast cancer cell migration and invasion by targeting HOXA10. BMC Cancer. 12:1112012. View Article : Google Scholar : PubMed/NCBI
21	Carrera M, Bitu CC, de Oliveira CE, Cervigne NK, Graner E, Manninen A, Salo T and Coletta RD: HOXA10 controls proliferation, migration and invasion in oral squamous cell carcinoma. Int J Clin Exp Pathol. 8:3613–3623. 2015.PubMed/NCBI
22	Kim JW, Kim JY, Kim JE, Kim SK, Chung HT and Park CK: HOXA10 is associated with temozolomide resistance through regulation of the homologous recombinant DNA repair pathway in glioblastoma cell lines. Genes Cancer. 5:165–174. 2014.PubMed/NCBI
23	Zhang L, Wan Y, Jiang Y, Ma J, Liu J, Tang W, Wang X and Cheng W: Upregulation HOXA10 homeobox gene in endometrial cancer: Role in cell cycle regulation. Med Oncol. 31:522014. View Article : Google Scholar : PubMed/NCBI
24	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
25	Jougla E: Survival of cancer patients in Europe (EUROCARE study). Rev Epidemiol Sante Publique. 44:473–475. 1996.(In French). PubMed/NCBI
26	Coward JI, Middleton K and Murphy F: New perspectives on targeted therapy in ovarian cancer. Int J Womens Health. 7:189–203. 2015. View Article : Google Scholar : PubMed/NCBI
27	Zaman MS, Maher DM, Khan S, Jaggi M and Chauhan SC: Current status and implications of microRNAs in ovarian cancer diagnosis and therapy. J Ovarian Res. 5:442012. View Article : Google Scholar : PubMed/NCBI
28	Nikitina EG, Urazova LN and Stegny VN: MicroRNAs and human cancer. Exp Oncol. 34:2–8. 2012.PubMed/NCBI
29	Kim TH, Song JY, Park H, Jeong JY, Kwon AY, Heo JH, Kang H, Kim G and An HJ: miR-145, targeting high-mobility group A2, is a powerful predictor of patient outcome in ovarian carcinoma. Cancer Lett. 356:937–945. 2015. View Article : Google Scholar : PubMed/NCBI
30	Xu S, Fu GB, Tao Z, OuYang J, Kong F, Jiang BH, Wan X and Chen K: MiR-497 decreases cisplatin resistance in ovarian cancer cells by targeting mTOR/P70S6K1. Oncotarget. 6:26457–26471. 2015. View Article : Google Scholar : PubMed/NCBI
31	Guan Y, Yao H, Zheng Z, Qiu G and Sun K: MiR-125b targets BCL3 and suppresses ovarian cancer proliferation. Int J Cancer. 128:2274–2283. 2011. View Article : Google Scholar : PubMed/NCBI
32	Lee YS and Dutta A: MicroRNAs in cancer. Annu Rev Pathol. 4:199–227. 2009. View Article : Google Scholar : PubMed/NCBI
33	Nygren MK, Tekle C, Ingebrigtsen VA, Mäkelä R, Krohn M, Aure MR, Nunes-Xavier CE, Perälä M, Tramm T, Alsner J, et al: Identifying microRNAs regulating B7-H3 in breast cancer: The clinical impact of microRNA-29c. Br J Cancer. 110:2072–2080. 2014. View Article : Google Scholar : PubMed/NCBI
34	Kim JJ, Taylor HS, Lu Z, Ladhani O, Hastings JM, Jackson KS, Wu Y, Guo SW and Fazleabas AT: Altered expression of HOXA10 in endometriosis: Potential role in decidualization. Mol Hum Reprod. 13:323–332. 2007. View Article : Google Scholar : PubMed/NCBI
35	Kelly M, Daftary G and Taylor HS: An autoregulatory element maintains HOXA10 expression in endometrial epithelial cells. Am J Obstet Gynecol. 194:1100–1109. 2006. View Article : Google Scholar : PubMed/NCBI
36	Daftary GS, Troy PJ, Bagot CN, Young SL and Taylor HS: Direct regulation of beta3-integrin subunit gene expression by HOXA10 in endometrial cells. Mol Endocrinol. 16:571–579. 2002. View Article : Google Scholar : PubMed/NCBI
37	Cheng W, Liu J, Yoshida H, Rosen D and Naora H: Lineage infidelity of epithelial ovarian cancers is controlled by HOX genes that specify regional identity in the reproductive tract. Nat Med. 11:531–537. 2005. View Article : Google Scholar : PubMed/NCBI
38	Shih IeM, Chen L, Wang CC, Gu J, Davidson B, Cope L, Kurman RJ, Xuan J and Wang TL: Distinct DNA methylation profiles in ovarian serous neoplasms and their implications in ovarian carcinogenesis. Am J Obstet Gynecol. 203(584): e1–22. 2010.
39	Pan BL, Tong ZW, Wu L, Pan L, Li JE, Huang YG, Li SD, Du SX and Li XD: Effects of MicroRNA-206 on osteosarcoma cell proliferation, apoptosis, migration and invasion by targeting ANXA2 through the AKT signaling pathway. Cell Physiol Biochem. 45:1410–1422. 2018. View Article : Google Scholar : PubMed/NCBI
40	Libório-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
41	Li B, Jin H, Yu Y, Gu C, Zhou X, Zhao N and Feng Y: HOXA10 is overexpressed in human ovarian clear cell adenocarcinoma and correlates with poor survival. Int J Gynecol Cancer. 19:1347–1352. 2009. View Article : Google Scholar : PubMed/NCBI