LncRNA GAS5 regulates apoptosis in ovarian cancer cells by regulating O-GlcNAcylation of GOLGA8B
Ovarian cancer therapy faces significant challenges, including late diagnosis, high recurrence rates, and chemoresistance. The long non-coding RNA GAS5 acts as a tumor suppressor and is downregulated in ovarian cancer, but the mechanism by which it regulates apoptosis remains unclear. This study aimed to reveal the molecular mechanism of GAS5-mediated apoptosis in ovarian cancer cells. We found that GAS5 expression was lower in ovarian cancer tissues and cell lines. Low GAS5 expression was related to worse prognosis. Functional experiments showed that increasing GAS5 expression promoted apoptosis in ovarian cancer cells. Mechanistically, increasing GAS5 raised the mRNA level of the Golgi protein-GOLGA8B. But it reduced the GOLGA8B protein level. Furthermore, GAS5 overexpression shortened the protein half-life and decreased the stability of GOLGA8B, suggesting the involvement of post-transcriptional regulation. Further investigation revealed that GAS5 inhibits O-GlcNAc transferase (OGT), thereby reducing O-GlcNAcylation of GOLGA8B.Ser58 was found to be the key modification site of GOLGA8B. Functionally, GOLGA8B was shown to activate the STAT3 signaling pathway.GAS5 inhibits STAT3 phosphorylation by downregulating GOLGA8B, thereby inducing cell apoptosis. In vivo animal experiments confirmed that GAS5 overexpression suppresses tumor growth. In summary, this study reveals that GAS5 regulates ovarian cancer cell apoptosis by modulating the O-GlcNAcylation of GOLGA8B, which in turn affects the STAT3 signaling pathway, providing a new potential therapeutic target for ovarian cancer.