ALYREF regulates the m5C modification and stability of BIRC5 mRNA to promote ovarian cancer progression

Ovarian cancer (OC) is the most dangerous cancer among gynecological tumors, which poses a significant threat to women's health worldwide. 5-methylcytosine (m5C) plays a significant role in regulating tumor development. The RNA methyltransferase Aly/REF export factor (ALYREF) is one of the m5C-modified RNA-reading proteins. Although it was reported that ALREF played a facilitating role in a variety of cancers, the mechanism of ALYREF in OC was unclear.

Bioinformatics and western blot were applied to analyze the expression levels of ALYREF both in tissues and cells of OC. Cellular behaviors were detected by CCK8, colony formation assay, EdU assay and flow cytometry. Then, glucose and lactate levels were measured to assess glycolysis. Next, RIP, MeRIP and qRT-PCR were used to explore the interaction between ALYREF and baculoviral IAP repeat containing 5 (BIRC5). At last, the roles of ALYREF and BIRC5 in vivo were proved by constructing xenograft tumor models.

ALYREF was highly expressed both in tissues and cells of OC. Downregulated ALYREF alleviated cell proliferation, migration, invasion, cell cycle, and glycolysis, and promoted apoptosis. Moreover, ALYREF had binding sites with BIRC5, and their expressions in tumors were positively correlated. The anti-tumor effects due to the downregulation of ALYREF could be reverted by overexpression of BIRC5. Furthermore, ALYREF knockdown restrained the growth of OC in vivo.

ALYREF regulates BIRC5 mRNA by m5C modification and exerts oncogenic effects in OC.