The Role of RNA Modifications and RNA-modifying Proteins in Cancer Therapy and Drug Resistance

Abstract

The advent of new genome-wide sequencing technologies has uncovered abnormal RNA modifications and RNA editing in a variety of human cancers. The discovery of reversible RNA N6-methyladenosine (RNA: m⁶A) by fat mass and obesity-associated protein (FTO) demethylase has led to exponential publications on the pathophysiological functions of m⁶A and its corresponding RNA modifying proteins (RMPs) in the past decade. Some excellent reviews have summarized the recent progress in this field. Compared to the extent of research into RNA: m⁶A and DNA 5-methylcytosine (DNA: m⁵C), much less is known about other RNA modifications and their associated RMPs, such as the role of RNA: m⁵C and its RNA cytosine methyltransferases (RCMTs) in cancer therapy and drug resistance. In this review, we will summarize the recent progress surrounding the function, intramolecular distribution and subcellular localization of several major RNA modifications, including 5' cap N7-methylguanosine (m7G) and 2'-O-methylation (Nm), m⁶A, m⁵C, A-to-I editing, and the associated RMPs. We will then discuss dysregulation of those RNA modifications and RMPs in cancer and their role in cancer therapy and drug resistance.

Keywords: 5-methylcytosine (m5C); 5′ cap; Myc; N6-methyladenosine (m6A); NOL1/NOP2/sun domain (NSUN); adenosine-to-inosine editing (A-to-I); drug resistance; mTOR.