Role of m6A RNA Methylation in Thyroid Cancer Cell Lines

Int J Mol Sci. 2022 Sep 29;23(19):11516. doi: 10.3390/ijms231911516.

Abstract

N6-methyladenosine (m6A) is the most abundant internal modification of RNA in eukaryotic cells, and, in recent years, it has gained increasing attention. A good amount of data support the involvement of m6A modification in tumorigenesis, tumor progression, and metastatic dissemination. However, the role of this RNA modification in thyroid cancer still remains poorly investigated. In this study, m6A-related RNA methylation profiles are compared between a normal thyroid cell line and different thyroid cancer cell lines. With this approach, it was possible to identify the different patterns of m6A modification in different thyroid cancer models. Furthermore, by silencing METTL3, which is the main player in the RNA methylation machinery, it was possible to evaluate the impact of m6A modification on gene expression in an anaplastic thyroid cancer model. This experimental approach allowed us to identify DDI2 as a gene specifically controlled by the m6A modification in anaplastic thyroid cancer cell lines. Altogether, these data are a proof of concept that RNA methylation widely occurs in thyroid cancer cell models and open a way forward in the search for new molecular patterns for diagnostic discrimination between benign and malignant lesions.

Keywords: METTL3; RNA methylation; epitranscriptome; m6A; thyroid cancer.

MeSH terms

  • Cell Line
  • Humans
  • Methylation
  • Methyltransferases / genetics
  • Methyltransferases / metabolism
  • RNA / metabolism
  • Thyroid Carcinoma, Anaplastic*
  • Thyroid Neoplasms* / genetics

Substances

  • RNA
  • Methyltransferases
  • METTL3 protein, human

Grants and funding

L.A. and C.M. post-doctoral fellowships are funded by “Dipartimento di Area Medica” of the University of Udine. E.M. doctoral fellowship is funded by Dipartimento di Scienze agroalimentari, ambientali e animali of the University of Udine. No other financial assistance was received in support of the study.