The Effect of Hsa-miR-504 Targeting MUC16 in Ovarian Cancer Progression

Abstract

Ovarian cancer (OC) is the most fatal gynecological tumor. Early diagnosis of OC is difficult and recurrence rate is high after treatment. Studies on the early detection of OC lesions using nanotechnology and nanomaterials are limited by the large number of OC subtypes and cannot achieve effective early detection. Understanding the molecular mechanism of OC and identifying new therapeutic targets is important. MUC16 is an important diagnostic indicator of OC, and hsa-miR-504 may be a potential biomarker of OC. However, the effects of miR-504 on cell cycle, apoptosis, and proliferation of OC and its relationship with MUC16 must be further clarified. The relationship between miR-504 and OC was determined by Gene Expression Omnibus (GEO) and meta-analysis, and the molecular pathways of miR-504 and MUC16 intervening in OC were screened by GSEA analysis. The expression of miR-504 and MUC16 in Skov3IP cells and their correlation with clinical features were detected by qRT-PCR and western blotting (WB). The correlation between miR-504 and MUC16 was detected with the luciferase reporter assay. The effects of miR-504 and MUC16 on the cell cycle and apoptosis of Skov3IP cells were detected by flow cytometry. Meta-analysis of the GSE dataset showed that miR-504 expression is downregulated in OC (95% CI [−0.39; 0.40]). GSEA enrichment analysis combined with literature review showed that MUC16 is involved in the TP53 signaling pathway to regulate cell proliferation and apoptosis. qRT-PCR and WB confirmed that the expression of MUC16 was upregulated and miR-504 was downregulated in Skov3IP cells. A luciferase reporter assay confirmed that miR-504 targeted MUC16. In OC, downregulation of miR-504 can increase the expression of MUC16, inhibit OC cell apoptosis, and promote OC cell proliferation. The miR-504 target MUC16 may participate in OC through the TP53 signaling pathway. miR-504 can be used as a potential tumor biomarker of OC.