MicroRNA-234-3p inhibits the progression of ovarian cancer by regulating the WNK2/Ras/MEK/ERG signaling pathway tears or tendinopathy: a double-blind randomized controlled trial

Abstract

Ovarian cancer (OC) is the most lethal gynecological malignancy, characterized by late diagnosis, high recurrence rates, and limited effective targeted therapies. MicroRNAs (miRNAs) play critical roles in OC progression by post-transcriptionally regulating oncogenes and tumor suppressors. In this study, we investigated the expression, function, and molecular mechanism of miR-234-3p in OC. We found that miR-234-3p was significantly downregulated in OC tissues and cell lines compared with normal ovarian epithelium. Overexpression of miR-234-3p suppressed OC cell proliferation, colony formation, and invasion in vitro, whereas its inhibition promoted these malignant phenotypes. Bioinformatics prediction and dual-luciferase reporter assays identified WNK2 as a direct target of miR-234-3p. WNK2 was upregulated in OC tissues, correlated with advanced clinicopathological features and poor prognosis, and promoted cell proliferation and invasion both in vitro and in vivo. Mechanistically, WNK2 activated the Ras/MEK/ERK/ERG signaling pathway, as evidenced by increased RAS-GTP levels and elevated phosphorylation of MEK and ERK. Rescue experiments demonstrated that WNK2 partially reversed the tumor-suppressive effects of miR-234-3p. Collectively, our findings reveal that miR-234-3p inhibits OC progression by directly targeting WNK2 and thereby attenuating the Ras/MEK/ERK/ERG pathway. These results highlight the miR-234-3p/WNK2 axis as a potential diagnostic biomarker and therapeutic target for ovarian cancer.