MicroRNA‑19b promotes the migration and invasion of ovarian cancer cells by inhibiting the PTEN/AKT signaling pathway

Liu,Dan‑Tong; Yao,Hai‑Rong; Li,Yan‑Ying; Song,Yang‑Yang; Su,Meng‑Ya

doi:10.3892/ol.2018.8695

MicroRNA‑19b promotes the migration and invasion of ovarian cancer cells by inhibiting the PTEN/AKT signaling pathway

Authors:
- Dan‑Tong Liu
- Hai‑Rong Yao
- Yan‑Ying Li
- Yang‑Yang Song
- Meng‑Ya Su
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Affiliations: Department of Gynecology, Cangzhou Central Hospital, Cangzhou, Hebei 061001, P.R. China
Published online on: May 10, 2018 https://doi.org/10.3892/ol.2018.8695
Pages: 559-565

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Abstract

Local and systemic metastasis is the main reason for the poor survival rate of patients with ovarian cancer (OC). MicroRNAs (miRNAs/miRs) are short non‑coding RNAs that serve critical roles in the initiation and progression of OC. The present study demonstrated that expression of miR‑19b was significantly increased in OC tissues and cell lines. Analysis of clinicopathological features revealed that the increased expression of miR‑19b was associated with advanced International Federation of Gynecology and Obstetrics stage and lymphatic metastasis of OC patients. Loss‑of‑function experiments demonstrated that the silencing of miR‑19b reduced the migration and invasion of OVCAR‑3 cells; contrarily, the overexpression of miR‑19b facilitated the migration and invasion of CAOV‑3 cells. Furthermore, miR‑19b regulated the expression of phosphatase and tensin homolog (PTEN) and the activity of the PTEN/RAC serine/threonine‑protein kinase pathway in vitro. Notably, the results of dual‑luciferase reporter assays indicated that PTEN was a direct downstream target of miR‑19b in OC. Taken together, the results of the current study demonstrated that miR‑19b serves an oncogenic role in the progression of OC, and could potentially act as a biomarker and therapeutic target for OC patients.

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1	Siegel R, Ma J, Zou Z and Jemal A: Cancer statistics, 2014. CA Cancer J Clin. 64:9–29. 2014. View Article : Google Scholar : PubMed/NCBI
2	Banerjee S and Kaye SB: New strategies in the treatment of ovarian cancer: Current clinical perspectives and future potential. Clin Cancer Res. 19:961–968. 2013. View Article : Google Scholar : PubMed/NCBI
3	Mezzanzanica D: Ovarian cancer: A molecularly insidious disease. Chin J Cancer. 34:1–3. 2015. View Article : Google Scholar : PubMed/NCBI
4	Chien JR, Aletti G, Bell DA, Keeney GL, Shridhar V and Hartmann LC: Molecular pathogenesis and therapeutic targets in epithelial ovarian cancer. J Cell Biochem. 102:1117–1129. 2007. View Article : Google Scholar : PubMed/NCBI
5	Hennessy BT, Coleman RL and Markman M: Ovarian cancer. Lancet. 374:1371–1382. 2009. View Article : Google Scholar : PubMed/NCBI
6	Mendell JT: MicroRNAs: Critical regulators of development, cellular physiology and malignancy. Cell Cycle. 4:1179–1184. 2005. View Article : Google Scholar : PubMed/NCBI
7	Calin GA and Croce CM: MicroRNA signatures in human cancers. Nat Rev Cancer. 6:857–866. 2006. View Article : Google Scholar : PubMed/NCBI
8	Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D, Sweet-Cordero A, Ebert BL, Mak RH, Ferrando AA, et al: MicroRNA expression profiles classify human cancers. Nature. 435:834–838. 2005. View Article : Google Scholar : PubMed/NCBI
9	Chong GO, Jeon HS, Han HS, Son JW, Lee YH, Hong DG, Lee YS and Cho YL: Differential microRNA expression profiles in primary and recurrent epithelial ovarian cancer. Anticancer Res. 35:2611–2617. 2015.PubMed/NCBI
10	Llauradó M, Majem B, Altadill T, Lanau L, Castellví J, Sánchez-Iglesias JL, Cabrera S, De la Torre J, Díaz-Feijoo B, Pérez-Benavente A, et al: MicroRNAs as prognostic markers in ovarian cancer. Mol Cell Endocrinol. 390:73–84. 2014. View Article : Google Scholar : PubMed/NCBI
11	Iorio MV, Visone R, Di Leva G, Donati V, Petrocca F, Casalini P, Taccioli C, Volinia S, Liu CG, Alder H, et al: MicroRNA signatures in human ovarian cancer. Cancer Res. 67:8699–8707. 2007. View Article : Google Scholar : PubMed/NCBI
12	Taylor DD and Gercel-Taylor C: MicroRNA signatures of tumor-derived exosomes as diagnostic biomarkers of ovarian cancer. Gynecol Oncol. 110:13–21. 2008. View Article : Google Scholar : PubMed/NCBI
13	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
14	Lin Q, Chen T, Lin Q, Lin G, Lin J, Chen G and Guo L: Serum miR-19a expression correlates with worse prognosis of patients with non-small cell lung cancer. J Surg Oncol. 107:767–771. 2013. View Article : Google Scholar : PubMed/NCBI
15	Li J, Yang S, Yan W, Yang J, Qin YJ, Lin XL, Xie RY, Wang SC, Jin W, Gao F, et al: MicroRNA-19 triggers epithelial-mesenchymal transition of lung cancer cells accompanied by growth inhibition. Lab Invest. 95:1056–1070. 2015. View Article : Google Scholar : PubMed/NCBI
16	Ohira T, Naohiro S, Nakayama Y, Osaki M, Okada F, Oshimura M and Kugoh H: miR-19b regulates hTERT mRNA expression through targeting PITX1 mRNA in melanoma cells. Sci Rep. 5:82012015. View Article : Google Scholar : PubMed/NCBI
17	Zhang X, Yu H, Lou JR, Zheng J, Zhu H, Popescu NI, Lupu F, Lind SE and Ding WQ: MicroRNA-19 (miR-19) regulates tissue factor expression in breast cancer cells. J Biol Chem. 286:1429–1435. 2011. View Article : Google Scholar : PubMed/NCBI
18	Baumhoer D, Zillmer S, Unger K, Rosemann M, Atkinson MJ, Irmler M, Beckers J, Siggelkow H, von Luettichau I, Jundt G, et al: MicroRNA profiling with correlation to gene expression revealed the oncogenic miR-17-92 cluster to be up-regulated in osteosarcoma. Cancer Genet. 205:212–219. 2012. View Article : Google Scholar : PubMed/NCBI
19	Wang F, Li T, Zhang B, Li H, Wu Q, Yang L, Nie Y, Wu K, Shi Y and Fan D: MicroRNA-19a/b regulates multidrug resistance in human gastric cancer cells by targeting PTEN. Biochem Biophys Res Commun. 434:688–694. 2013. View Article : Google Scholar : PubMed/NCBI
20	Javadi S, Ganeshan DM, Qayyum A, Iyer RB and Bhosale P: Ovarian cancer, the revised FIGO staging system, and the role of imaging. AJR Am J Roentgenol. 206:1351–1360. 2016. View Article : Google Scholar : PubMed/NCBI
21	Ma W, Yu Q, Jiang J, DU X, Huang L, Zhao L and Zhou QI: miR-517a is an independent prognostic marker and contributes to cell migration and invasion in human colorectal cancer. Oncol Lett. 11:2583–2589. 2016. 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. 2001. View Article : Google Scholar : PubMed/NCBI
23	Shen Y, Shen R, Ge L, Zhu Q and Li F: Fibrillar type I collagen matrices enhance metastasis/invasion of ovarian epithelial cancer via β1 integrin and PTEN signals. Int J Gynecol Cancer. 22:1316–1324. 2012. View Article : Google Scholar : PubMed/NCBI
24	Liu H, Pan Y, Han X, Liu J and Li R: MicroRNA-216a promotes the metastasis and epithelial-mesenchymal transition of ovarian cancer by suppressing the PTEN/AKT pathway. Onco Targets Ther. 10:2701–2709. 2017. View Article : Google Scholar : PubMed/NCBI
25	Lou Y, Yang X, Wang F, Cui Z and Huang Y: MicroRNA-21 promotes the cell proliferation, invasion and migration abilities in ovarian epithelial carcinomas through inhibiting the expression of PTEN protein. Int J Mol Med. 26:819–827. 2010. View Article : Google Scholar : PubMed/NCBI
26	Georgescu MM: PTEN tumor suppressor network in PI3K-Akt pathway control. Genes Cancer. 1:1170–1177. 2010. View Article : Google Scholar : PubMed/NCBI
27	Lengyel E: Ovarian cancer development and metastasis. Am J Pathol. 177:1053–1064. 2010. View Article : Google Scholar : PubMed/NCBI
28	Mezzanzanica D, Bagnoli M, De Cecco L, Valeri B and Canevari S: Role of microRNAs in ovarian cancer pathogenesis and potential clinical implications. Int J Biochem Cell Biol. 42:1262–1272. 2010. View Article : Google Scholar : PubMed/NCBI
29	Li X, Xie W, Xie C, Huang C, Zhu J, Liang Z, Deng F, Zhu M, Zhu W, Wu R, et al: Curcumin modulates miR-19/PTEN/AKT/p53 Axis to suppress bisphenol A-induced MCF-7 breast cancer cell proliferation. Phytother Res. 28:1553–1560. 2014. View Article : Google Scholar : PubMed/NCBI
30	Hanahan D and Weinberg RA: Hallmarks of cancer: The next generation. Cell. 144:646–674. 2011. View Article : Google Scholar : PubMed/NCBI
31	JiaZeng X: MicroRNA and tumor metastasis. Cancer Res Clinic. 21:65–67. 2009.
32	Yang H, Kong W, He L, Zhao JJ, O'Donnell JD, Wang J, Wenham RM, Coppola D, Kruk PA, Nicosia SV and Cheng JQ: MicroRNA expression profiling in human ovarian cancer: miR-214 induces cell survival and cisplatin resistance by targeting PTEN. Cancer Res. 68:425–433. 2008. View Article : Google Scholar : PubMed/NCBI