CSTF2 mediated mRNA N<sup>6</sup>-methyladenosine modification drives pancreatic ductal adenocarcinoma m<sup>6</sup>A subtypes.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 37816727.
- Also identified by DOI 10.1038/s41467-023-41861-y and PMC identifier 10564946.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
N<sup>6</sup>-methyladenosine (m<sup>6</sup>A) modification of gene transcripts plays critical roles in cancer. Here we report transcriptomic m<sup>6</sup>A profiling in 98 tissue samples from 65 individuals with pancreatic ductal adenocarcinoma (PDAC). We identify 17,996 m<sup>6</sup>A peaks with 195 hyper-methylated and 93 hypo-methylated in PDAC compared with adjacent normal tissues. The differential m<sup>6</sup>A modifications distinguish two PDAC subtypes with different prognosis outcomes. The formation of the two subtypes is driven by a newly identified m<sup>6</sup>A regulator CSTF2 that co-transcriptionally regulates m<sup>6</sup>A installation through slowing the RNA Pol II elongation rate during gene transcription. We find that most of the CSTF2-regulated m<sup>6</sup>As have positive effects on the RNA level of host genes, and CSTF2-regulated m<sup>6</sup>As are mainly recognized by IGF2BP2, an m<sup>6</sup>A reader that stabilizes mRNAs. These results provide a promising PDAC subtyping strategy and potential therapeutic targets for precision medicine of PDAC.
Medical subject headings
- Pancreatic Neoplasms
- Carcinoma, Pancreatic Ductal