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Cited by 71RNA modifications and cancerCancer-related molecular mechanisms researchEpigenetics and DNA Methylation

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METTL3 promotes pancreatic cancer proliferation and stemness by increasing stability of ID2 mRNA in a m6A-dependent manner

Chen, Jiaoshun, Zhang, Haoxiang, Xiu, Chaoyang, Gao, Chenggang, Wu, Shihong, Bai, Jianwei, Shen, Qiang, Yin, Tao·2023·Cancer Letters
DOI 10.1016/j.canlet.2023.216222
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Abstract

In eukaryotes, N 6-methyladenosine (m6A) is the most prevalent epigenetic alteration. Methyltransferase-like 3 (METTL3) is a key player in the control of m6A, although its function in pancreatic cancer is incompletely understood. In this study, we examined the role that METTL3 plays in pancreatic cancer cell proliferation and stemness. We discovered that in pancreatic cancer cells, METTL3-mediated m6A alterations regulate ID2 as a downstream target. The stability of ID2 mRNA was decreased and m6A modification was effectively eliminated by METTL3 knockdown in pancreatic cancer cells. We also demonstrate that m6a-YTHDF2 is necessary for the METTL3-mediated stabilization of ID2 mRNA. Additionally, we show that ID2 controls the stemness molecules NANOG and SOX2 via the PI3K-AKT pathway to support pancreatic cancer growth and stemness maintenance. Our data suggest that METTL3 may post-transcriptionally upregulate ID2 expression in an m6A-YTHDF2-dependent manner to further promote the stabilization of ID2 mRNA, which may be a new target for pancreatic cancer treatment.

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Metadata

Authors
Chen, J., Zhang, H., Xiu, C., Gao, C., Wu, S., Bai, J., Shen, Q., & Yin, T.
Affiliations
  • Wuhan Union Hospital (CN)
  • Chengdu University of Traditional Chinese Medicine (CN)
  • Louisiana State University Health Sciences Center New Orleans (US)
Corresponding author
Yin, Tao
ORCID
Venue
Cancer Letters
Publisher
Elsevier BV
Published
2023-07
Volume
565
Pages
216222
ISSN
0304-3835 (ISSN-L)
DOI
10.1016/j.canlet.2023.216222
OpenAlex
W4377011231
Cited by
71
References
1
Citations by year
2026: 13 · 2025: 33 · 2024: 25
FWCI
6.31
Type
journal article
Language
en
Open access
closed
Licence
Locations
  • Cancer Letters (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Natural Science Foundation of China (81772564, 82173196)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA modifications and cancer
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
Keywords
METTL3, pancreatic cancer, m6A RNA methylation, Id2, mRNA stability, YTHDF2, cancer stemness, Nanog, SOX2, PI3K/Akt signaling, cell proliferation, post-transcriptional regulation
MeSH terms
Humans, Methyltransferases, Pancreatic Neoplasms, RNA, Messenger, Transcription Factors, Phosphatidylinositol 3-Kinases, Cell Proliferation, Inhibitor of Differentiation Protein 2

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