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Identification of gene signature in mock and miR-625-3p-transfected ovarian cancer cells

ABSTRACT: Advanced-stage high-grade serous ovarian cancer (HGSC) is a disease that is difficult to manage due to its heterogeneous clinical behavior. No reliable prediction of response to chemotherapy is currently available and the overall survival rate remains poor. Herein, we sought to determine the molecular mechanisms by which microRNAs (miRNAs) confer chemoresistance in ovarian cancer and to demonstrate the efficacy of targeting miRNAs to sensitize HGSC to cisplatin treatment. An miRNA signature for intrinsic chemoresistance was identified. Amongst all the downregulated miRNAs in the chemo-refractory samples, only miR-625-3p was associated with poorer overall survival and progression-free survival rates. Further functional studies showed that overexpression of miR-625-3p significantly decreased cisplatin resistance in ovarian cancer cells both in vitro and in vivo. SSX2IP was confirmed to be the direct gene target of miR-625-3p and its upregulation abrogated miR-625-3p-mediated cisplatin resistance by enhancing exosomal export of cisplatin in ovarian cancer cells. These findings provided a new paradigm for intrinsic cisplatin resistance acquisition by HGSC cells, which will be crucial for developing new treatment strategies for ovarian cancer based on upregulation of miR-625-3p or downregulation of SSX2IP to enhance cisplatin sensitivity and improve patient survival rates.

ORGANISM(S): Homo sapiens

PROVIDER: GSE301530 | GEO | 2026/03/18

REPOSITORIES: GEO

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Expression data from high-grade serous ovarian carcinomas (HGSC), clear cell ovarian carcinomas (CCC) and ovarian surface epithelium (OSE)

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