ML323 suppresses the progression of ovarian cancer via regulating USP1-mediated cell cycle

Abstract

Background: Ubiquitin specific protease 1 (USP1) tightly correlates with poor prognosis of multiple cancers. However, whether USP1 underlies ovarian cancer (OV) progression remains unclarified.Methods: First, GSEA strategy and WGCNA analysis were used to screen for anti-ovarian cancer drugs and furthern optimal module, respectively. In addition, functional enrichments of module genes were realized by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Kaplan-Meier was then employed to analyze the prognostic impact of USP1 expression on OV patients. Cell proliferation and cell cycle assays were used to confirm biological functions of USP1 in the final.Results: Through the forementioned methods, we obtained five candidate drugs against OV from 353 anticancer drugs, and proposed ML323 as a novel anti-OV drug. As our hypothesized, ML323 significantly inhibited the proliferation of OV cells. Combined with WGCNA and KEGG analysis, the turquoise module was related to ML323, together with cell cycle. USP1 was subsequently identified as a target of ML323 and according to the TCGA database, USP1 negatively correlated with prognosis in OV, and its reduction and ML323-treatment both inhibited the proliferation of OV cells, blocking the S phase of cell cycle in vitro.Conclusion: Taken together, ML323 exerts its inhibitory effect on the proliferation of OV cells by targeting USP1-regulated cell cycle, providing a therapeutical strategy and potential target against OV.