KMT2D Regulates the NCOA6/THRB Signal Axis through Epigenetic Modification to Promote the Migration and Invasion of Papillary Thyroid Cancer

Front Biosci (Landmark Ed). 2023 Jan 18;28(1):17. doi: 10.31083/j.fbl2801017.

Abstract

Background: The histone lysine methyltransferase Histone-lysine N-methytransferase 2D (KMT2D) is a common mutated gene in a variety of cancers, including papillary thyroid cancer (PTC). However, the mechanism of KMT2D on the progression of PTC remains unclear.

Methods: In this study, quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting were used to evaluate KMT2D expression between human normal cell (Nthy-ori 3-1) and PTC cells (TPC1, IHH-4 and BCPAP). Proliferation, migration and invasion of TPC1, IHH-4 and BCPAP were assessed by Cell Counting Kit-8 (CCK-8), Wound-healing assay and Transwell assay. The mechanism of KMT2D on thyroid papillary cancer was explored with Chromatin immunoprecipitation assay (ChIP), qRT-PCR and Western blotting.

Results: The expression of KMT2D in PTC cells was significantly increased. Downregulation of KMT2D significantly decreased the proliferation, migration and invasion of PTC cells, which was correlated with decreased expression levels of H3K4me2, H3K9me2, NCOA6 and THRB. Meanwhile, ChIP assay demonstrated that KMT2D was associated with NCOA6.

Conclusions: Study have shown that the downregulation of KMT2D reduces proliferation, migration and invasion of thyroid papillary carcinoma cells through epigenetic modification of NCOA6/THRB signal axis. These results provide a new insight into the role of KMT2D in migration and invasion of PTC.

Keywords: KMT2D; epigenetic modification; invasion; migration; papillary thyroid cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biological Assay
  • Blotting, Western
  • DNA-Binding Proteins* / genetics
  • Epigenesis, Genetic*
  • Genes, erbA
  • Histone-Lysine N-Methyltransferase / genetics
  • Humans
  • Neoplasm Proteins* / genetics
  • Nuclear Receptor Coactivators
  • Thyroid Cancer, Papillary / genetics
  • Thyroid Neoplasms* / genetics

Substances

  • Histone-Lysine N-Methyltransferase
  • NCOA6 protein, human
  • Nuclear Receptor Coactivators
  • KMT2D protein, human
  • DNA-Binding Proteins
  • Neoplasm Proteins