miR-33a-3p regulates METTL3-mediated AREG stability and alters EMT to inhibit pancreatic cancer invasion and metastasis

Recent studies have shown that amphoteric regulatory protein (AREG), a member of the epidermal growth factor (EGF) family, is expressed in many cancers and is an independent prognostic indicator for patients with pancreatic cancer, but whether AREG is regulated at the epigenetic level to promote the...

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Published in:Scientific reports 2023-08, Vol.13 (1), p.13587-13587, Article 13587
Main Authors: Su, Xiaowen, Lai, Tiantian, Tao, Yue, Zhang, Yong, Zhao, Changyong, Zhou, Junjing, Chen, Enhong, Zhu, Maoqun, Zhang, Shuo, Wang, Bei, Mao, Yong, Hu, Hao
Format: Article
Language:English
Subjects:
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Amphiregulin - metabolism
Cell migration
Cell proliferation
Clonal deletion
Epidermal Growth Factor
Epigenetics
Epithelial-Mesenchymal Transition
Humanities and Social Sciences
Humans
Metastases
Methyltransferase
Methyltransferases - genetics
MicroRNAs - genetics
mRNA stability
multidisciplinary
N6-methyladenosine
Pancreatic cancer
Pancreatic Neoplasms
Pancreatic Neoplasms - genetics
Pancreatic Neoplasms - metabolism
Pancreatic Neoplasms - pathology
Science
Science (multidisciplinary)
Tumor cell lines
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Summary:Recent studies have shown that amphoteric regulatory protein (AREG), a member of the epidermal growth factor (EGF) family, is expressed in many cancers and is an independent prognostic indicator for patients with pancreatic cancer, but whether AREG is regulated at the epigenetic level to promote the development of pancreatic cancer (PC) has not been elucidated. Our results support the notion that AREG is overexpressed in pancreatic cancer tissues and cell lines. Functionally, the deletion of AREG impedes pancreatic cancer (PC) cell proliferation, migration, and invasion. In addition, we identified and validated that methyltransferase-like 3 (METTL3) induced the m 6 A modification on AREG and facilitated the stability of AREG mRNA after sequencing. Additionally, we obtained experimental evidence that miR-33a-3p targets and inhibits METTL3 from taking action, as predicted by using the miRDB and RNAinter. Remediation experiments showed that miR-33a-3p inhibits PC progression through METTL3. In summary, this research reveals that miR-33a-3p inhibits m 6 A-induced stabilization of AREG by targeting METTL3, which plays a key role in the aggressive progression of PC. AREG could be a potential target for PC treatment.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-023-39506-7