N1-methyladenosine modification in cancer biology: Current status and future perspectives

Abstract

Post-transcriptional modifications in RNAs regulate their biological behaviors and functions. N¹-methyladenosine (m¹A), which is dynamically regulated by writers, erasers and readers, has been found as a reversible modification in tRNA, mRNA, rRNA and long non-coding RNA (lncRNA). m¹A modification has impacts on the RNA processing, structure and functions of targets. Increasing studies reveal the critical roles of m¹A modification and its regulators in tumorigenesis. Due to the positive relevance between m¹A and cancer development, targeting m¹A modification and m¹A-related regulators has been of attention. In this review, we summarized the current understanding of m¹A in RNAs, covering the modulation of m¹A modification in cancer biology, as well as the possibility of targeting m¹A modification as a potential target for cancer diagnosis and therapy.

Keywords: AAA, Abdominal aortic aneurysm; ALKBH1, Alkb homologue 1; ALKBH3, Alkb homologue 3; ALKBH7, Alkb homologue 7; AML, Acute myeloid leukemia; BC, Breast cancer; BLCA, Bladder urothelial carcinoma; CC, Colon cancer; CRC, Colorectal cancer; Cancer biology; Diagnosis; FTO, Fat mass and obesity-associated protein; GBM, Glioblastoma multiforme; GI, Gastrointestinal cancer; HCC, Hepatocellular carcinoma; M1A; MA2, Meclofenamic acid 2; NML, Nucleomethylin; NSAID, Nonsteroidal anti-inflammatory drug; NSCLC, Non-small-cell lung cancer; Nm, Ribose-methylation; OC, Ovarian cancer; OSCC, Oral squamous cell carcinoma; PAAD, Pancreatic cancer; PC, Prostate cancer; R-2HG, R-2-hydroxyglutarate; RNA; SAM, S-adenosyl-l-methionine; TME, Tumor microenvironment; TRMT10C, tRNA methyltransferase 10C; TRMT6, tRNA methyltransferase 6; TRMT61A, tRNA methyltransferase 61A; TRMT61B, tRNA methyltransferase 61B; Therapy; UTR, 5′ untranslated region; YTH, YT521-B homology; YTHDC1, YTH domain containing 1; YTHDF1, YTH domain family protein 1; YTHDF2, YTH domain family protein 2; YTHDF3, YTH domain family protein 3; cyt-tRNA, Cytoplasmic tRNA; hm5C, 5-hydroxymethylcytosine; lncRNA, Long non-coding RNA; m1A, N1-methyladenosine; m1I, 1-methylinosine; m5C, 5-methylcytidine; m6A, N6-methyladenosine; m6Am, N6,2′-O-dimethyladenosine; m7G, N7-methylguanosine; mt-tRNA, Mitochondrial tRNA; tDRs, tRNA-derived small RNAs; tRFs, tRNA fragments.