RNA methylation regulators contribute to poor prognosis of hepatocellular carcinoma associated with the suppression of bile acid metabolism: a multi-omics analysis

RNA methylation has been known to promote the initiation and progression of many types of cancer, including hepatocellular carcinoma (HCC). To fully understand the importance of this post-transcriptional modification in HCC, a thorough investigation that combines different patterns of RNA methylation is urgently needed. In this study, we investigated the regulators of the three most common types of RNA methylation: m6A, N1-methyladenosine (m1A) and 5-methylcytosine (m5C). Based on the genomic and proteomic data, we constructed a classifier consisting of seven RNA methylation regulators. This classifier performed well and robustly predicted the prognosis of HCC patients. By analysis using this classifier, we found that the primary bile acid biosynthesis pathway was mostly downregulated in high-risk HCC patients. Furthermore, we found that the gene expression patterns regulated by several bile acids were similar to those regulated by some well-defined anti-tumor compounds, indicating that bile acid metabolism plays a crucial role in the progression of HCC, and the related metabolites can be used as the potential agents for HCC treatments. Moreover, our study revealed a crosstalk between RNA methylation and bile acid regulators, demonstrating a novel mechanism of the downregulation of bile acid metabolism in HCC and providing new insights into how RNA methylation regulators affect the oncogenesis of HCC.