ALKBH5 promotes ovarian cancer progression by activating Notch2 signaling.

Abstract

Background: ALKBH5, one of the RNA N6-methyladenosine (m6A) demethyltransferases, has been suggested to be involved in the progression of several cancers. The aim of this study was to investigate clinical significance and biological functions of ALKBH5 in promoting ovarian cancer progression.

Results: We found a significant upregulation of ALKBH5 expression in ovarian cancer tissues compared with normal tissues. Correlation analyses indicated an association between heightened ALKBH5 expression and FIGO stage, as well as lymph node metastasis. Importantly, increased ALKBH5 expression indicated shorter progression-free survival and overall survival. Moreover, we found that hypoxia induced an increase in ALKBH5 expression in ovarian cancer via an HIF-1α-dependent mechanism. Loss-of-function assays demonstrated that ALKBH5 knockdown inhibited ovarian cancer cell progression both in vitro and in vivo. Furthermore, we found that knockdown of ALKBH5-meidated m6A demethylation decreased Notch2 mRNA stability and expression, resulting in the inhibition of cell proliferation, invasion and metastasis in OC cells.

Conclusion: In summary, our findings demonstrated that ALKBH5 promotes the progression of ovarian cancer by activating Notch2 signaling, and suggested that ALKBH5 functions as an oncogene and may serve as a prognostic biomarker and therapeutic target in ovarian cancer.