HDAC7/c-Myc signaling pathway promotes the proliferation and metastasis of choroidal melanoma cells

Cell Death Dis. 2023 Jan 18;14(1):38. doi: 10.1038/s41419-022-05522-0.

Abstract

Choroidal melanoma (CM) is the most common type of diagnosed uveal melanoma (UM), which is prone to metastasis and exhibits a poor prognosis. The molecular mechanisms underlying CM progression need further elucidation to research effective therapeutic strategies. Histone deacetylase 7 (HDAC7) is very important in regulating cancer progression, but the significance and effect of HDAC7 on CM progression are unclear. In the present study, we found that HDAC7 is overexpressed in CM tissues versus normal tissues. We built HDAC7 overexpressing CM cell lines to study the functions of HDAC7 in CM progression and verified that upregulation of HDAC7 promoted the proliferation and metastasis of CM cells, while pharmacological inhibition of HDAC7 suppressed both the proliferation and metastasis of CM cells. Furthermore, we found that the aforementioned cancer-promoting effect of HDAC7 was mediated by c-Myc. Targeted inhibition of c-Myc inhibited CM progression by interfering with the HDAC7/c-Myc signaling pathway. Our study highlighted the function of targeting the HDAC7/c-Myc signaling pathway to intervene in the pathological process of CM, which provides potential therapeutic strategies for CM treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Proliferation / genetics
  • Histone Deacetylases / genetics
  • Histone Deacetylases / metabolism
  • Humans
  • Melanoma* / genetics
  • Proto-Oncogene Proteins c-myc* / genetics
  • Proto-Oncogene Proteins c-myc* / metabolism
  • Signal Transduction

Substances

  • Proto-Oncogene Proteins c-myc
  • Histone Deacetylases
  • HDAC7 protein, human

Supplementary concepts

  • Uveal melanoma