Author Correction: RNA cytosine methylation and methyltransferases mediate chromatin organization and 5-azacytidine response and resistance in leukaemia

Abstract

In the originally published version of this Article, the GAPDH loading control blot in Fig. 1a was inadvertently replaced with a duplicate of the DNMT2 blot in the same panel during assembly of the figure. This has now been corrected in both the PDF and HTML versions of the Article.

The RNA Methyltransferase NSUN2 and Its Potential Roles in Cancer

“…Given that alterations involving increased expression of NSUN2 are common in breast cancer [ 93 , 95 , 98 ], colon cancer [ 92 , 93 ], and lung cancer as suggested in the suggestions above, molecularly targeting this RNMT would appear to an attractive approach moving forward. While studies on NSUN2 have used azacytidine in the past [ 24 , 110 ], due to the previously poor responses to this drug observed in the past, newer approaches may be necessary to elicit effective responses in patients. For example, it may be possible to use agents targeting NSUN2 to increase the number of patients that may be suitable for checkpoint inhibitors.…”

“…Loss of the region containing NSUN3 has been reported as a common loss in lung adenocarcinomas of never-smokers at a frequency of 15% [ 109 ], and interestingly, this was the only coding gene in the region lost [ 109 ]. Mutation of NSUN3 has been shown to result in reduced mitochondrial protein translation and respiration [ 2 ], while some evidence has shown a role for NSUN3 in nuclear transcriptional regulation in leukemic cells [ 110 ].…”

“…Molecularly targeting m5C RNMTs using drugs previously developed to target DNMTs is a potential possibility as demonstrated from using Aza-IP [ 24 ] and preliminary in vitro data in leukemic cells, where novel RNA:m5C/RCMT-mediated chromatin structures form that modulate 5-AZA response/resistance [ 110 ]. Alternatively, it may be possible to target NSUN2-mediated events such as that shown for the lncRNA NMR in esophageal cancer, whereby NSUN2-methylated NMR interacts with the chromatin remodeling factor Bromodomain PHD Finger Transcription Factor (BPTF) [ 35 , 118 ] to regulate resistance to cisplatin.…”

The Interplay Between the Genetic and Immune Landscapes of AML: Mechanisms and Implications for Risk Stratification and Therapy

“…In addition to its effect on DNA, azacitadine has been reported to inhibit the RNA methyltransferase, DNMT2 (96) suggesting that it's mechanism of action in myeloid neoplasms may be linked to modification of RNA. Consistent with this possibility, in a recent report, distinct RNA 5-methylcytosine methyltransferase chromatin complexes were demonstrated to mediate sensitivity vs. resistance to azacitadine (97). Up-regulation of antigen presentation pathways, such as MHC expression, are part of the mechanism by which HMA are described to recalibrate the immune micoenvironment promoting anti-tumor responses (98–103).…”

Environmental epitranscriptomics

“…The cause of NSUN2 up-regulation in solid tumours such as colorectal and oral cancers can be increased copy number (Okamoto et al, 2012). There is already emerging evidence for an impact of RNA m 5 C on drug sensitivity (Cheng et al, 2018), suggesting that this may be a fruitful avenue of research in the near future.…”