ALYREF mediates RNA m5C modification to promote hepatocellular carcinoma progression
Chen Xue, Xinyu Gu, Qiuxian Zheng, Qingmiao Shi, Xin Yuan, Yuanshuai Su, Junjun Jia, Jianwen Jiang, Juan Lu, Lanjuan Li
Abstract
The incidence of hepatocellular carcinoma (HCC) is increasing in many countries due to hepatic virus infection and unhealthy diet habits, and the unsatisfactory overall survival rate calls for novel treatments with higher efficacy. 1 Recent studies have shown that RNA modifications are likely to participate in the progression of HCC, 2 suggesting new methods for tumor growth control. Specifically, 5-methylcytosine (m 5 C) is one of the most interesting RNA modification types, as accumulating evidence suggests its role in the promotion of HCC tumorigenesis. 3 The RNA methyltransferase Aly/REF export factor (ALYREF) is considered one type of “reader” protein located in the nucleus that recognizes and binds directly with m 5 C sites in RNA and facilitates the export of RNA from the nucleus to the cytoplasm. 4 Notably, ALYREF is considered a promising target for diagnosis and prognosis prediction. 5 However, until now, the low number of related studies has limited the understanding of the mechanism of the HCC-promoting effects of ALYREF. To further elucidate the oncogenic roles of ALYREF in HCC, we assessed the expression levels of ALYREF in clinical samples and HCC cell lines and explored the effects of ALYREF deficiency by both in vitro and in vivo experiments and m 5 C-methylated RNA immunoprecipitation sequencing (m 5 C-MeRIP-Seq).