The diverse role of RNA methylation in esophageal cancer

Abstract

Esophageal cancer is one of the major life-threatening diseases in the world. RNA methylation is the most common post-transcriptional modification and a wide-ranging regulatory system controlling gene expression. Numerous studies have revealed that dysregulation of RNA methylation is critical for cancer development and progression. However, the diverse role of RNA methylation and its regulators in esophageal cancer remains to be elucidated and summarized. In this review, we focus on the regulation of major RNA methylation, including m ⁶A, m ⁵C, and m ⁷G, as well as the expression patterns and clinical implications of its regulators in esophageal cancer. We systematically summarize how these RNA modifications affect the "life cycle" of target RNAs, including mRNA, microRNA, long non-coding RNA, and tRNA. The downstream signaling pathways associated with RNA methylation during the development and treatment of esophageal cancer are also discussed in detail. Further studies on how these modifications function together in the microenvironment of esophageal cancer will draw a clearer picture of the clinical application of novel and specific therapeutic strategies.

Keywords: 5-methylcytosine; 7-methylguanosine; N6-methyladenosine; RNA methylation; esophageal cancer; post-transcriptional modification; tumor microenvironment.

Figure 1

Expression modulation of RNA methylation regulators in esophageal cancer The expressions of m 6A regulators METTL3, ALKBH5, IGF2BP2, HNRNPC, and YTHDC2, and m 5C regulators NSUN2 and TET1-3 are modulated by drugs, carcinogens, transcription factors (TFs), miRNAs and many other modalities.

Figure 2

Diverse effect of m ⁶A writers on the RNA life cycle and cellular function in esophageal cancer m 6A writers METTL3, METTL14, and WTAP mediate m 6A modification of target RNAs and promote esophageal cancer progression.

Figure 3

Diverse effect of m ⁶A erasers and readers on the RNA life cycle and cellular function in esophageal cancer (A) m 6A erasers FTO and ALKBH5 mediate the demethylation of target RNAs and affect the biological function of esophageal cancer. (B) m 6A readers YTHDF1 and IGF2BP2 exert different effects on m 6A-modified RNAs and mediate ESCC progression.

Figure 4

Diverse effect of m ⁵C and m ⁷G regulators on the RNA life cycle and cellular function in esophageal cancer (A) m 5C writer NSUN2 and reader YBX1 exert different effects on m 5C-modified RNAs and mediate ESCC progression. (B) m 7G writers METTL1/WDR4 promote tRNA expression through m 7G modification and mediate ESCC progression.