Effect of integrin‑linked kinase gene silencing on microRNA expression in ovarian cancer

Yuan,Dandan; Zhao,Yilei; Wang,Yang; Che,Jianhua; Tan,Wenhua; Jin,Yuxia; Wang,Fei; Li,Peiliang; Fu,Shuyan; Liu,Qian; Zhu,Wenliang

doi:10.3892/mmr.2017.7523

Effect of integrin‑linked kinase gene silencing on microRNA expression in ovarian cancer

Authors:
- Dandan Yuan
- Yilei Zhao
- Yang Wang
- Jianhua Che
- Wenhua Tan
- Yuxia Jin
- Fei Wang
- Peiliang Li
- Shuyan Fu
- Qian Liu
- Wenliang Zhu
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Affiliations: Department of Obstetrics and Gynecology, Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China, Department of Pharmacy, First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China, Institute of Clinical Pharmacology, Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China
Published online on: September 19, 2017 https://doi.org/10.3892/mmr.2017.7523
Pages: 7267-7276
Copyright: © Yuan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Integrin‑linked kinase (ILK) is overexpressed in ovarian cancer (OC), and ILK gene silencing results in apoptosis in OC cells. In the present study, the mechanism by which ILK induces apoptosis was explored from the perspective of microRNA (miRNA) expression. Alterations in the global miRNA expression profile were detected using a miRNA microarray after OC cells were transduced with an ILK small hairpin RNA lentivirus. ILK silencing led to a significant upregulation of 14 miRNAs by at least 1.5‑fold. These findings were validated by reverse transcription‑quantitative polymerase chain reaction. A pathway analysis of experimentally validated target genes revealed the inhibition of multiple cancer‑associated signaling pathways and the wnt signaling pathway. Compared with cells transfected with scrambled RNA, the ILK‑silenced cells had remarkably lower expression of wnt ligands (wnt3a, wnt4 and wnt5a) and downstream β‑catenin. ILK silencing led to apoptosis of OC cells and impaired the migratory ability. Taken together, the present results suggested that miRNA‑mediated wnt pathway alterations are involved in the anti‑apoptotic role of ILK in OC. It was also indicated that ILK silencing reduced the ability of OC cells to adhere to fibronectin, which may lead to unstable focal contact. Consistently, the phosphorylation levels of focal adhesion kinase and RAC‑α serine/threonine protein kinase were downregulated. The present work demonstrated the first global miRNA expression profile of OC cells when ILK was inhibited, and this expression profile may provide a basis for the development of biomarkers and therapeutic targets for OC.

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