DNMT3B-mediated FAM111B methylation promotes papillary thyroid tumor glycolysis, growth and metastasis

Int J Biol Sci. 2022 Jul 4;18(11):4372-4387. doi: 10.7150/ijbs.72397. eCollection 2022.


Over the past decades, the incidence of thyroid cancer (TC) rapidly increased all over the world, with the papillary thyroid cancer (PTC) accounting for the vast majority of TC cases. It is crucial to investigate novel diagnostic and therapeutic targets for PTC and explore more detailed molecular mechanisms in the carcinogenesis and progression of PTC. Based on the TCGA and GEO databases, FAM111B is downregulated in PTC tissues and predicts better prognosis in PTC patients. FAM111B suppresses the growth, migration, invasion and glycolysis of PTC both in vitro and in vivo. Furthermore, estrogen inhibits FAM111B expression by DNMT3B methylation via enhancing the recruitment of DNMT3B to FAM111B promoter. DNMT3B-mediated FAM111B methylation accelerates the growth, migration, invasion and glycolysis of PTC cells. In clinical TC patient specimens, the expression of FAM111B is inversely correlated with the expressions of DNMT3B and the glycolytic gene PGK1. Besides, the expression of FAM111B is inversely correlated while DNMT3B is positively correlated with glucose uptake in PTC patients. Our work established E2/DNMT3B/FAM111B as a crucial axis in regulating the growth and progression of PTC. Suppression of DNMT3B or promotion of FAM111B will be potential promising strategies in the estrogen induced PTC.

Keywords: DNMT3B; Estrogen; FAM111B; Glycolysis; Papillary thyroid cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle Proteins* / genetics
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • DNA (Cytosine-5-)-Methyltransferases* / genetics
  • DNA Methyltransferase 3B
  • Estrogens
  • Gene Expression Regulation, Neoplastic
  • Glycolysis
  • Humans
  • Methylation
  • Thyroid Cancer, Papillary / genetics
  • Thyroid Cancer, Papillary / pathology
  • Thyroid Neoplasms* / genetics
  • Thyroid Neoplasms* / pathology


  • Cell Cycle Proteins
  • Estrogens
  • FAM111B protein, human
  • DNA (Cytosine-5-)-Methyltransferases