KMT2A facilitates the epithelial-to-mesenchymal transition and the progression of ovarian cancer.

Abstract

Epithelial-mesenchymal transition (EMT) plays critical roles in cancer progression and metastasis. Thus, the exploration of the molecular mechanism regulating EMT would provide potential opportunities for the therapy of metastatic ovarian cancer (OC). Herein, we investigated the putative role of KMT2A in modulating EMT and metastasis in OC. The expression of KMT2A in OC was detected by Western blot and immunohistochemistry and its relationship with clinicopathological factors was analyzed. The effect of KMT2A on the biological behavior of OC cells was examined. Moreover, the expressions of EMT-associated proteins were detected in vivo and vitro by Western blot, immunofluorescence, and immunohistochemistry. KMT2A was highly expressed in OC cell lines and tissues and was positively correlated with advanced International Federation of Gynecology and Obstetrics (FIGO) stage, pathological grade, and metastasis. KMT2A overexpression was correlated with poor prognosis. Suppression of KMT2A inhibited OC cells proliferation, migration, and invasion and induced their apoptosis in vitro and vivo. In contrast, the ectopic expression of KMT2A had the opposite effects. Furthermore, KMT2A knockdown inhibited TGF-β-induced EMT in OC and reduced the phosphorylation levels of Smad2. Taken together, these observations demonstrate that KMT2A could promote the malignant behavior of OC by activating TGF-β/Smad signaling pathway and may be a potential prognostic biomarker and therapeutic target for OC.