MEX3A promotes the malignant progression of ovarian cancer by regulating intron retention in TIMELESS

Abstract

Abstract The latest research shows that RNA-binding proteins (RBPs) could serve as novel potential targets for cancer therapy. We used bioinformatics analysis to screen and identify the key RBPs in ovarian cancer, from which we found that Mex-3 RNA Binding Family Member A (MEX3A) was intimately associated with the clinical prognosis of ovarian cancer. Nevertheless, little is known about its biological roles in ovarian cancer. In this case, we observed that MEX3A was highly overexpressed in fresh-frozen ovarian cancer tissues. MEX3A knockdown suppressed the development and invasion of ovarian cancer cells, while MEX3A overexpression promoted the proliferation and invasion of ovarian cancer cells. Mechanistically, TIMELESS was the critical downstream target gene of MEX3A, as demonstrated through alternative splicing event analysis based on RNA-seq. MEX3A knockdown resulted in retention of intron twenty-three of TIMELESS mRNA and decreased TIMELESS mRNA owing to stimulation of nonsense-mediated RNA decay (NMD). Additionally, we found that TIMELESS overexpression with MEX3A knockdown partially restored the proliferation ability of ovarian cancer cells. The results of this paper demonstrated that the MEX3A/TIMELESS signaling pathway was a key regulator of ovarian cancer, and MEX3A was a novel possible treatment target for ovarian cancer patients.