FTO/IGF2BP2-mediated N6 methyladenosine modification in invasion and metastasis of thyroid carcinoma via CDH12.

Cell Death Dis

Clinical Medical Research Center, The First Affiliated Hospital, Hengyang Medical School, University of South China, 421001, Hengyang, Hunan, China.

Published: October 2024

AI Article Synopsis

  • Epigenetic reprogramming, particularly through m6A RNA modification, significantly influences cancer progression, with increased levels noted in papillary and anaplastic thyroid cancers.
  • The down-regulation of the demethylase FTO contributes to higher m6A levels, promoting invasion and metastasis of thyroid cancer via the epithelial-to-mesenchymal transition (EMT) pathway.
  • CDH12 is identified as a key target gene affected by FTO, with IGF2BP2 playing a crucial role in stabilizing CDH12 mRNA, suggesting that targeting FTO, IGF2BP2, and CDH12 could be therapeutic strategies for aggressive thyroid cancers.

Article Abstract

Epigenetic reprogramming plays a critical role in cancer progression of cancer, and N6-methyladenosine (m6A) is the most common RNA modification in eukaryotes. The purpose of this study was to explore the related modification mode of m6A regulator construction and evaluate the invasion and migration of thyroid cancer. Our results showed that m6A levels were significantly increased in papillary thyroid cancer (PTC) and anaplastic thyroid cancer (ATC) samples, which may have been induced by the down-regulation of demethylase fat mass and obesity-associated gene (FTO). Moreover, FTO inhibited PTC and ATC invasion and metastasis through the epithelial-to-mesenchymal transition (EMT) pathway in vivo and in vitro. Mechanistically, an m6A-mRNA epitranscriptomic microarray showed that Cadherin 12 (CDH12) is the key target gene mediated by FTO in an m6A-dependent manner. CDH12 promotes invasion and metastasis through the EMT pathway in thyroid cancer, both in vivo and in vitro. Furthermore, we found that insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) is an important m6A reading protein, that regulates the stability of CDH12 mRNA and mediates EMT progression, thereby promoting the invasion and metastasis of PTC and ATC. Thus, FTO, IGF2BP2 and CDH12 may be effective therapeutic targets for PTC and ATC with significant invasion or distant metastasis. Schematic summary of FTO-IGF2BP2 axis in modulation of CDH12 mRNA m6A and upregulation of CDH12 expression in the invasion and metastasis of thyroid carcinoma.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11461506PMC
http://dx.doi.org/10.1038/s41419-024-07097-4DOI Listing

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