MicroRNA‑16 inhibits migration and invasion via regulation of the Wnt/β‑catenin signaling pathway in ovarian cancer

Li,Nan; Yang,Liang; Sun,Yanan; Wu,Xiaohua

doi:10.3892/ol.2019.9923

MicroRNA‑16 inhibits migration and invasion via regulation of the Wnt/β‑catenin signaling pathway in ovarian cancer

Authors:
- Nan Li
- Liang Yang
- Yanan Sun
- Xiaohua Wu
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Affiliations: Department of Gynecology, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050017, P.R. China, Department of Neurosurgery, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050017, P.R. China, Department of Obstetrics and Gynecology, Bethune International Peace Hospital of People's Liberation Army, Shijiazhuang, Hebei 050082, P.R. China, Department of Obstetrics and Gynecology, Hebei Medical University, Shijiazhuang, Hebei 050017, P.R. China
Published online on: January 14, 2019 https://doi.org/10.3892/ol.2019.9923
Pages: 2631-2638
Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

As small non‑coding RNA molecules, microRNAs (miRs) function in the regulation of tumorigenesis. Proliferation in ovarian cancer is considered to be associated with miR‑16; however, the role of miR‑16 in the migration and invasion of ovarian cancer cells remains unclear. The results of the present study demonstrated that miR‑16 expression is downregulated in the ovarian cancer SKOV3 and OVCAR3 cell lines compared with that in normal ovarian epithelial cells (OECs). miR‑16 overexpression inhibited the proliferation, migration and invasion of SKOV3 and OVCAR3 cells, and decreased the expression of matrix metallopeptidase (MMP)2 and MMP9. Additionally, miR‑16 upregulated the expression of cadherin 1, an intercellular adhesion molecule, and downregulated the expression of some mesenchymal markers, including snail family transcriptional repressor 2, snail family transcriptional repressor 1, Vimentin, twist family BHLH transcription factor 1 and cadherin 2 in SKOV3 and OVCAR3 cells. Furthermore, it was indicated that miR‑16 overexpression in SKOV3 and OVCAR3 cells resulted in a significant increase in anti‑glycogen synthase kinase 3 β expression and a decrease in the expression of Wnt family member 3A, β‑catenin, MYC proto‑oncogene, BHLH transcription factor and cyclin D1 compared with the NC group. The results of the present study indicated that miR‑16 exerts a suppressive effect on cell migration and invasion in ovarian cancer in vitro, through inactivation of the Wnt/β‑catenin signaling pathway. The data suggest that miR‑16 may be a potential therapeutic agent for the treatment and prevention of ovarian cancer.

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1	Siegel RL, Miller KD and Jemal A: Cancer statistics, 2016. CA Cancer J Clin. 66:7–30. 2016. View Article : Google Scholar : PubMed/NCBI
2	Prahm KP, Novotny GW, Høgdall C and Høgdall E: Current status on microRNAs as biomarkers for ovarian cancer. APMIS. 124:337–355. 2016. View Article : Google Scholar : PubMed/NCBI
3	Yeung TL, Leung CS, Yip KP, Au Yeung CL, Wong ST and Mok SC: Cellular and molecular processes in ovarian cancer metastasis. A review in the theme: Cell and molecular processes in cancer metastasis. Am J Physiol Cell Physiol. 309:C444–C456. 2015. View Article : Google Scholar : PubMed/NCBI
4	Wang Y, Kim S and Kim IM: Regulation of metastasis by microRNAs in ovarian cancer. Front Oncol. 4:1432014. View Article : Google Scholar : PubMed/NCBI
5	Zhang L, Nadeem L, Connor K and Xu G: Mechanisms and therapeutic targets of microRNA-associated chemoresistance in epithelial ovarian cancer. Curr Cancer Drug Targets. 16:429–441. 2016. View Article : Google Scholar : PubMed/NCBI
6	Wang ZH and Xu CJ: Research progress of MicroRNA in early detection of ovarian cancer. Chin Med J (Engl). 128:3363–3370. 2015. View Article : Google Scholar : PubMed/NCBI
7	Langhe R: microRNA and ovarian cancer. Adv Exp Med Biol. 889:119–151. 2015. View Article : Google Scholar : PubMed/NCBI
8	Wei J, Zhang L, Li J, Zhu S, Tai M, Mason CW, Chapman JA, Reynolds EA, Weiner CP and Zhou HH: MicroRNA-205 promotes cell invasion by repressing TCF21 in human ovarian cancer. J Ovarian Res. 10:332017. View Article : Google Scholar : PubMed/NCBI
9	Wei LQ, Liang HT, Qin DC, Jin HF, Zhao Y and She MC: MiR-212 exerts suppressive effect on SKOV3 ovarian cancer cells through targeting HBEGF. Tumour Biol. 35:12427–12434. 2014. View Article : Google Scholar : PubMed/NCBI
10	Hanlon K, Rudin CE and Harries LW: Investigating the targets of MIR-15a and MIR-16-1 in patients with chronic lymphocytic leukemia (CLL). PLoS One. 4:e71692009. View Article : Google Scholar : PubMed/NCBI
11	Bottoni A, Piccin D, Tagliati F, Luchin A, Zatelli MC and degli Uberti EC: miR-15a and miR-16-1 down-regulation in pituitary adenomas. J Cell Physiol. 204:280–285. 2005. View Article : Google Scholar : PubMed/NCBI
12	Di Leva G and Croce CM: The role of microRNAs in the tumorigenesis of ovarian cancer. Front Oncol. 3:1532013. View Article : Google Scholar : PubMed/NCBI
13	Bhattacharya R, Nicoloso M, Arvizo R, Wang E, Cortez A, Rossi S, Calin GA and Mukherjee P: MiR-15a and MiR-16 control Bmi-1 expression in ovarian cancer. Cancer Res. 69:9090–9095. 2009. View Article : Google Scholar : PubMed/NCBI
14	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
15	Pietruszewska W, Bojanowska-Poźniak K and Kobos J: Matrix metalloproteinases MMP1, MMP2, MMP9 and their tissue inhibitors TIMP1, TIMP2, TIMP3 in head and neck cancer: An immunohistochemical study. Otolaryngol Pol. 70:32–43. 2016. View Article : Google Scholar : PubMed/NCBI
16	Deng J, Wang L, Chen H, Hao J, Ni J, Chang L, Duan W, Graham P and Li Y: Targeting epithelial-mesenchymal transition and cancer stem cells for chemoresistant ovarian cancer. Oncotarget. 7:55771–55788. 2016. View Article : Google Scholar : PubMed/NCBI
17	Zhou XM, Zhang H and Han X: Role of epithelial to mesenchymal transition proteins in gynecological cancers: Pathological and therapeutic perspectives. Tumour Biol. 35:9523–9530. 2014. View Article : Google Scholar : PubMed/NCBI
18	McCubrey JA, Fitzgerald TL, Yang LV, Lertpiriyapong K, Steelman LS, Abrams SL, Montalto G, Cervello M, Neri LM, Cocco L, et al: Roles of GSK-3 and microRNAs on epithelial mesenchymal transition and cancer stem cells. Oncotarget. 8:14221–14250. 2017. View Article : Google Scholar : PubMed/NCBI
19	Ghahhari NM and Babashah S: Interplay between microRNAs and WNT/β-catenin signalling pathway regulates epithelial-mesenchymal transition in cancer. Eur J Cancer. 51:1638–1649. 2015. View Article : Google Scholar : PubMed/NCBI
20	Zhu L and Fang J: The structure and clinical roles of MicroRNA in colorectal cancer. Gastroenterol Res Pract. 2016:13603482016. View Article : Google Scholar : PubMed/NCBI
21	Shukla KK, Misra S, Pareek P, Mishra V, Singhal B and Sharma P: Recent scenario of microRNA as diagnostic and prognostic biomarkers of prostate cancer. Urol Oncol. 35:92–101. 2017. View Article : Google Scholar : PubMed/NCBI
22	Shah MY, Ferrajoli A, Sood AK, Lopez-Berestein G and Calin GA: microRNA therapeutics in cancer-an emerging concept. EBioMedicine. 12:34–42. 2016. View Article : Google Scholar : PubMed/NCBI
23	Pal MK, Jaiswar SP, Dwivedi VN, Tripathi AK, Dwivedi A and Sankhwar P: MicroRNA: A new and promising potential biomarker for diagnosis and prognosis of ovarian cancer. Cancer Biol Med. 12:328–341. 2015.PubMed/NCBI
24	Li X, Ling N, Bai Y, Dong W, Hui GZ, Liu D, Zhao J and Hu J: MiR-16-1 plays a role in reducing migration and invasion of glioma cells. Anat Rec (Hoboken). 296:427–432. 2013. View Article : Google Scholar : PubMed/NCBI
25	Wu WL, Wang WY, Yao WQ and Li GD: Suppressive effects of microRNA-16 on the proliferation, invasion and metastasis of hepatocellular carcinoma cells. Int J Mol Med. 36:1713–1719. 2015. View Article : Google Scholar : PubMed/NCBI
26	Ekinci T, Ozbay PO, Yiğit S, Yavuzcan A, Uysal S and Soylu F: The correlation between immunohistochemical expression of MMP-2 and the prognosis of epithelial ovarian cancer. Ginekol Pol. 85:121–130. 2014. View Article : Google Scholar : PubMed/NCBI
27	Tan H, He Q, Gong G, Wang Y, Li J, Wang J, Zhu D and Wu X: miR-382 inhibits migration and invasion by targeting ROR1 through regulating EMT in ovarian cancer. Int J Oncol. 48:181–190. 2016. View Article : Google Scholar : PubMed/NCBI
28	Amankwah EK, Lin HY, Tyrer JP, Lawrenson K, Dennis J, Chornokur G, Aben KK, Anton-Culver H, Antonenkova N, Bruinsma F, et al: Epithelial-mesenchymal transition (EMT) gene variants and epithelial ovarian cancer (EOC) risk. Genet Epidemiol. 39:689–697. 2015. View Article : Google Scholar : PubMed/NCBI
29	Takai M, Terai Y, Kawaguchi H, Ashihara K, Fujiwara S, Tanaka T, Tsunetoh S, Tanaka Y, Sasaki H, Kanemura M, et al: The EMT (epithelial-mesenchymal-transition)-related protein expression indicates the metastatic status and prognosis in patients with ovarian cancer. J Ovarian Res. 7:762014. View Article : Google Scholar : PubMed/NCBI
30	Wang Q, Li X, Zhu Y and Yang P: MicroRNA-16 suppresses epithelial-mesenchymal transition-related gene expression in human glioma. Mol Med Rep. 10:3310–3314. 2014. View Article : Google Scholar : PubMed/NCBI
31	Wang H, Zhang Y, Wu Q, Wang Y-B and Wang W: miR-16 mimics inhibit TGF-β1-induced epithelial-to-mesenchymal transition via activation of autophagy in non-small cell lung carcinoma cells. Oncol Rep. 39:247–254. 2018.PubMed/NCBI
32	Bodnar L, Stanczak A, Cierniak S, Smoter M, Cichowicz M, Kozlowski W, Szczylik C, Wieczorek M and Lamparska-Przybysz M: Wnt/β-catenin pathway as a potential prognostic and predictive marker in patients with advanced ovarian cancer. J Ovarian Res. 7:162014. View Article : Google Scholar : PubMed/NCBI
33	Arend RC, Londoño-Joshi AI, Straughn JM Jr..Buchsbaum DJ: The Wnt/β-catenin pathway in ovarian cancer: A review. Gynecol Oncol. 131:772–779. 2013. View Article : Google Scholar : PubMed/NCBI
34	Wu Y, Ginther C, Kim J, Mosher N, Chung S, Slamon D and Vadgama JV: Expression of Wnt3 activates Wnt/β-catenin pathway and promotes EMT-like phenotype in trastuzumab-resistant HER2-overexpressing breast cancer cells. Mol Cancer Res. 10:1597–1606. 2012. View Article : Google Scholar : PubMed/NCBI
35	Kwon YJ, Baek HS, Ye DJ, Shin S, Kim D and Chun YJ: CYP1B1 enhances cell proliferation and metastasis through induction of EMT and activation of Wnt/β-catenin signaling via Sp1 upregulation. PLoS One. 11:e01515982016. View Article : Google Scholar : PubMed/NCBI
36	Sonderegger S, Haslinger P, Sabri A, Leisser C, Otten JV, Fiala C and Knöfler M: Wingless (Wnt)-3A induces trophoblast migration and matrix metalloproteinase-2 secretion through canonical Wnt signaling and protein kinase B/AKT activation. Endocrinology. 151:211–220. 2010. View Article : Google Scholar : PubMed/NCBI