Role of Main RNA Methylation in Hepatocellular Carcinoma: N6-Methyladenosine, 5-Methylcytosine, and N1-Methyladenosine

Abstract

RNA methylation is considered a significant epigenetic modification, a process that does not alter gene sequence but may play a necessary role in multiple biological processes, such as gene expression, genome editing, and cellular differentiation. With advances in RNA detection, various forms of RNA methylation can be found, including N6-methyladenosine (m6A), N1-methyladenosine (m1A), and 5-methylcytosine (m5C). Emerging reports confirm that dysregulation of RNA methylation gives rise to a variety of human diseases, particularly hepatocellular carcinoma. We will summarize essential regulators of RNA methylation and biological functions of these modifications in coding and noncoding RNAs. In conclusion, we highlight complex molecular mechanisms of m6A, m5C, and m1A associated with hepatocellular carcinoma and hope this review might provide therapeutic potent of RNA methylation to clinical research.

Correlation Between the RNA Methylation Genes and Immune Infiltration and Prognosis of Patients with Hepatocellular Carcinoma: A Pan-Cancer Analysis

“…Based on the abovementioned analysis and previous articles, genes had an important and complex role in HCC. 19 The genes whose fold changes were >1.5 and with FDR adjusted p-value < 0.05 were determined as differential genes (DEGs). 20 Figure 5A shows the association between DEGs, except for YTHDF3 and ALYREF , and most DEGs were positively correlated with each other, thereby suggesting the synergistic role of genes in the development of HCC.…”

“…In view of the role of RNA methylation genes in tumors, an RNA methylation gene-based prognostic model was established based on related studies. 19 Results showed that the model was a more accurate predictor of patient prognosis and that low-risk patients had a higher degree of immune infiltration and expression of immunosuppressive genes than low-risk patients. In mRNA, m5C modification can have a significant effect on metabolism.…”

“… 27 YTHDF1 acts as a “reader” of m6A, and there is growing evidence that facilitated translation positively regulates the role of YTHDF1 . 19 YTHDF1 plays “Promote proliferation, migration, and invasion” role in HCC via PI3K/Akt/mTOR. 19 , 26 , 28 In addition, GDSC and CTRP database analysis was performed to identify whether VAF-347, AZD1480, rigosertib, and KX2-391 are potential therapeutic agents in HCC.…”

“… 19 YTHDF1 plays “Promote proliferation, migration, and invasion” role in HCC via PI3K/Akt/mTOR. 19 , 26 , 28 In addition, GDSC and CTRP database analysis was performed to identify whether VAF-347, AZD1480, rigosertib, and KX2-391 are potential therapeutic agents in HCC. The sample size in the current study is a major limitation.…”

Identification of RNA Methylation-Related lncRNAs Signature for Predicting Hot and Cold Tumors and Prognosis in Colon Cancer

“…RNA methylation is considered an important process in epigenetic regulation, which occurs in mRNA and in ncRNA ( Xu et al, 2021 ). Various forms of RNA methylation exist depending on the site of methylation, including N1-methyladenosine (m1A), 5-methylcytosine (m5C), N6-methyladenosine (m6A), 7-methylguanosine (m7G), and 2-O-dimethyladenosine (m6Am) ( Xie et al, 2020 ).…”