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Published on: August 2, 2024
Effect of integrin‑linked kinase gene silencing on microRNA expression in ovarian cancer
Dandan Yuan1, Yilei Zhao2, Yang Wang2
1Department of Obstetrics and Gynecology, Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China.
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.
Insights
Integrin-linked kinase (ILK) silencing induces apoptosis in ovarian cancer (OC) cells by altering microRNA (miRNA) expression and inhibiting the Wnt signaling pathway. This study reveals potential new therapeutic targets for OC.
Area of Science:
- Molecular Biology
- Oncology
- Gene Regulation
Background:
- Integrin-linked kinase (ILK) is overexpressed in ovarian cancer (OC).
- ILK gene silencing induces apoptosis in OC cells.
- The underlying molecular mechanisms require further elucidation.
Purpose of the Study:
- To explore the mechanism of ILK-induced apoptosis in OC cells.
- To investigate the role of microRNA (miRNA) expression in this process.
- To identify potential therapeutic targets for OC.
Main Methods:
- Ovarian cancer cells were transduced with ILK small hairpin RNA lentivirus.
- Global miRNA expression profiling was performed using miRNA microarrays.
- Validation of miRNA expression and pathway analysis were conducted using reverse transcription-quantitative polymerase chain reaction and target gene analysis.
Main Results:
- ILK silencing significantly upregulated 14 miRNAs.
- Pathway analysis revealed inhibition of cancer-associated and Wnt signaling pathways.
- ILK silencing reduced Wnt ligands and β-catenin, leading to apoptosis and impaired migration.
Conclusions:
- miRNA-mediated Wnt pathway alterations are involved in the anti-apoptotic role of ILK in OC.
- ILK silencing reduces OC cell adhesion to fibronectin, affecting focal adhesion kinase and RAC-α serine/threonine protein kinase.
- This study provides the first global miRNA expression profile of ILK-inhibited OC cells, offering potential biomarkers and therapeutic targets.
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