microRNA-324-3p suppresses the aggressive ovarian cancer by targeting WNK2/RAS pathway

Abstract

Ovarian cancer (OC) has the highest mortality rate among gynecological cancers, which progresses owing to dysregulated microRNAs (miRNAs) expression. Our study attempts to reveal the mechanism by which decreased miR-324-3p expression suppresses OC proliferation. Quantitative real-time PCR, western blotting, in situ hybridization, and immunohistochemistry were performed to estimate miR-324-3p and WNK2 expression levels in OC cells and tissues. Cell Counting Kit-8, colony formation, EdU, and transwell assays were performed to analyze the influence of miR-324-3p and WNK2 on the proliferation and invasion ability of OC cells. Subsequently, xenograft models were established to examine the effects of WNK2 on OC cell proliferation in vivo, and databases and luciferase reporter assays were used to test the relationship between miR-324-3p and WNK2 expression. Then, we showed that miR-324-3p expression is decreased in OC cells and tissues, indicating its inhibitory effect on OC cell proliferation. Quantitative real-time PCR and luciferase reporter assays demonstrated that miR-324-3p inhibited WNK2 expression by directly binding to its 3’ untranslated region. WNK2, an upregulated kinase, promotes the proliferation and invasion of OC cells by activating the RAS pathway. Moreover, WNK2 can partly reverse the inhibitory effects of miR-324-3p on OC cell proliferation. Hence, we demonstrate that miR-324-3p suppressed ovarian cancer progression by targeting the WNK2 /RAS pathway. Our study provides theoretical evidence for the clinical application potential of miR-324-3p.

MicroRNA-mediated epigenetic regulation of HDAC8 and HDAC6: Functional significance in cervical cancer

“…This discrepancy emphasizes the complexity of miRNA regulation in cancer and necessitates comprehensive investigations to decipher context-specific roles. Intriguingly, our results align with emerging evidence that positions miR-324–3p as a tumor suppressor in various female-specific cancers, including breast and ovarian cancer [ 38 , [54] , [55] , [56] , [57] , [58] , [59] ]. These studies collectively highlight the potential multifaceted roles of miR-324–3p across distinct cancer types.…”

Role of RAS signaling in ovarian cancer

“…Moreover, phosphorylation modification levels of most proteins, most significantly RAS was observed when WNK2 was knocked down in SKOV3 and CAOV3 cell lines as analyzed by the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. 160 Reports from a recent study reveal that tumor progression was abolished upon the inhibition of RAS GTPase-activating protein SH3 domain-binding protein 1 (G3BP1) 161 involved in the RAS signaling pathway which is also involved in the development of several cancers such as breast, colon, and gastric cancer. 162 Figure 2.…”

“…Moreover, phosphorylation modification levels of most proteins, most significantly RAS was observed when WNK2 was knocked down in SKOV3 and CAOV3 cell lines as analyzed by the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. 160 …”

Expression profile analysis and the role of miRNA in breast adenocarcinoma

“…As these small molecules can affect almost all cellular activities, including cell cycle checkpoints, cell proliferation and apoptosis, and have a wide range of target genes. The dysregulation of miRNA expression is associated with various cancers by acting as tumor suppressors and oncogenes [6][7][8][9][10]. Circulating miRNAs also serve as potential biomarkers for diagnosis and prognosis of various cancers and other known diseases and syndromes [11][12][13].…”