WNK2 facilitates ovarian cancer progression by upregulating POU5F1B

Ovarian cancer (OC) remains the most lethal gynecological malignancy. Our previous work established that WNK lysine-deficient protein kinase 2 (WNK2) promotes OC cell proliferation and migration. To elucidate how WNK2 drives OC progression, we performed transcriptome sequencing to identify WNK2-regulated mRNAs and noncoding RNAs. Candidate targets were validated via qRT-PCR and Western blot. Functional assays (CCK-8, colony formation, Transwell) assessed the role of POU5F1B and its ability to rescue WNK2 knockdown effects. Given AKTs involvement downstream of POU5F1B, we measured AKT phosphorylation. Additionally, since WNK2 activates RAS (as previously shown), we tested whether RAS inhibition blocks WNK2-mediated POU5F1B regulation. POU5F1B exhibited oncogenic properties in OC cells. WNK2 upregulated POU5F1B mRNA and protein levels, and POU5F1B overexpression reversed tumor-suppressive effects caused by WNK2 knockdown. Mechanistically, WNK2 depletion reduced AKT phosphorylation, which was restored by POU5F1B overexpression. Furthermore, RAS inhibition abolished WNK2-driven POU5F1B upregulation, linking WNK2-RAS signaling to POU5F1B activation. Our study demonstrates that WNK2 promotes OC progression by upregulating POU5F1B, thereby activating AKT signaling. These findings solidify WNK2s oncogenic role and highlight its therapeutic potential in OC.