N(6)-methyladenosine methylation-regulated polo-like kinase 1 cell cycle homeostasis as a potential target of radiotherapy in pancreatic adenocarcinoma

Shotaro Tatekawa, Keisuke Tamari, Ryota Chijimatsu, Masamitsu Konno, Daisuke Motooka, Suguru Mitsufuji, Hirofumi Akita, Shogo Kobayashi, Yoshiki Murakumo, Yuichiro Doki, Hidetoshi Eguchi, Hideshi Ishii, Kazuhiko Ogawa

Research output: Contribution to journalArticlepeer-review

Abstract

In pancreatic cancer, methyltransferase-like 3 (METTL3), a N(6)-methyladenosine (m6A) methyltransferase, has a favorable effect on tumors and is a risk factor for patients’ prognosis. However, the details of what genes are regulated by METTL3 remain unknown. Several RNAs are methylated, and what genes are favored in pancreatic cancer remains unclear. By epitranscriptomic analysis, we report that polo-like kinase 1 (PLK1) is an important hub gene defining patient prognosis in pancreatic cancer and that RNA methylation is involved in regulating its cell cycle-specific expression. We found that insulin like growth factor 2 mRNA binding protein 2 (IGF2BP2) binds to m6A of PLK1 3′ untranslated region and is involved in upregulating PLK1 expression and that demethylation of this site activates the ataxia telangiectasia and Rad3-related protein pathway by replicating stress and increasing mitotic catastrophe, resulting in increased radiosensitivity. This suggests that PLK1 methylation is essential for cell cycle maintenance in pancreatic cancer and is a new therapeutic target.

Original languageEnglish
Article number11074
JournalScientific reports
Volume12
Issue number1
DOIs
Publication statusPublished - Dec 2022
Externally publishedYes

ASJC Scopus subject areas

  • General

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