ALKBH5 promotes autophagy and progression by mediating m6A methylation of lncRNA UBOX5-AS1 in endometriosis.

Abstract

Long noncoding RNA (lncRNA) and N6-methyladenosine (m6A) methylation modification have recently been suggested as potential functional modulators in ovarian endometriosis, however, the function and mechanism of m6A-modified lncRNA in ovarian endometriosis remain poorly understood. In this study, we demonstrated that lncRNA UBOX5-AS1 expression was significantly elevated in ovarian endometriosis tissue and primary ectopic endometrial stromal cells. The expression of lncRNA UBOX5-AS1, which has m6A modifications, was highly positively correlated with demethylase Alk B homologous protein 5 (ALKBH5) expression and autophagy. Functional studies revealed that increased ALKBH5 and lncRNA UBOX5-AS1 expression promoted cell autophagy, proliferation, and invasion in endometriosis in vitro. LncRNA UBOX5-AS1 mediates ALKBH5-regulated autophagy, proliferation, and invasion. ALKBH5-mediated autophagy facilitates cell proliferation, migration, and invasion. In vivo, the knockdown of ALKBH5 inhibited endometriotic lesion growth. Mechanistically, we observed that ALKBH5 mediated the m6A demethylation of lncRNA UBOX5-AS1 and promoted its expression. Thus, our findings highlight that ALKBH5/lncRNA UBOX5-AS1 might serve as potential targets for ovarian endometriosis therapy in the future.NEW & NOTEWORTHY In the present study, we investigated the role and potential molecular mechanism of long noncoding RNA (lncRNA) UBOX5-AS1 in ovarian endometriosis progression. Combined with the aforementioned, we proposed the hypothesis that lncRNA UBOX5-AS1 regulated by Alk B homologous protein 5 (ALKBH5)-mediated N6-methyladenosine (m6A) modification contributes to the progression of ovarian endometriosis progression.