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

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 ??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?? 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.

SUBMITTER: Yuan D 

PROVIDER: S-EPMC5865855 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature