Work

Adenosine‐to‐inosine editing of miR ‐200b‐3p is associated with the progression of high‐grade serous ovarian cancer

Year: 2025

Type: article

Abstract: Deamination of adenosine to inosine (A-to-I) in double-stranded microRNAs (miRNAs) has been demonstrated to affect their function as suppressors or oncogenes in various cancers. Nevertheless, the functional impact of miRNA editing in high-grade serous ovarian cancer (HGSOC) remains largely unexplored. Here, we identified A-to-I editing in miRNAs in 60 HGSOC tissues and 48 ovarian tissues received in nononcological procedures using small RNA sequencing (RNA-Seq). To investigate the functional impact of A-to-I modifications, we tested the effect of edited RNA mimics and small interfering RNA (siRNA)-mediated downregulation of the RNA-editing enzyme double-stranded RNA-specific editase Adar (ADAR1) on cell proliferation, migration and three-dimensional (3D) growth of HGSOC cells in vitro. Tumour suppressor miR-200b-3p was the most overedited miRNA in HGSOC tumours, and the increased editing level was associated with statistically significant worse overall survival (OS). Mechanistically, in contrast to wild-type miRNA, edited miR-200b-3p promoted cell proliferation, migration and formation of 3D spheroids. Loss of function of ADAR1 profoundly repressed proliferation, migration and 3D growth of HGSOC cells. RNA-Seq and Gene Set Enrichment Analysis (GSEA) analysis revealed that, whereas wild-type miR-200b-3p induced the apoptosis pathway, edited miR-200b-3p substantially inhibited cell-cycle-related pathways. Bioinformatic prediction revealed that edited miR-200b-3p gained the function to repress the expression of new targets, including tumour suppressor MAX interactor 1, dimerisation protein (MXI1), which was associated with a statistically significantly worse OS time in HGSOC patients. Our study reports the potential contribution of edited miR-200b-3p in HGSOC progression, and highlights its potential as a new therapeutic target.

Source: Molecular Oncology

DOI: 10.1002/1878-0261.70106