Pharmacological targeting of TNS3 with histone deacetylase inhibitor as a therapeutic strategy in esophageal squamous cell carcinoma

Aging (Albany NY). 2021 May 28;13(11):15336-15352. doi: 10.18632/aging.203091. Epub 2021 May 28.

Abstract

Histone acetylation which regulates about 2-10% of genes has been demonstrated to be involved in tumorigenesis of esophageal squamous cell carcinoma (ESCC). In this study, we investigated the treatment response of ESCC to selective histone deacetylase inhibitor (HDACi) LMK-235 and potential biomarker predicting the treatment sensitivity. We identified tensin-3 (TNS3) which was highly over-expressed in ESCC as one of the down-regulated genes in response to LMK-235 treatment. TNS3 was found positively correlated with the tumor malignancy and poor prognosis in the patients. Silencing TNS3 significantly inhibited ESCC cell proliferation both in vitro and in vivo, sensitizing the treatment response to LMK-235. Our findings provide an insight into understanding the oncogenic role of TNS3 in ESCC and its clinical application for HDAC targeted therapy of ESCC.

Keywords: LMK-235; esophageal squamous cell carcinoma; histone acetylation; histone deacetylase inhibitors; tensin-3.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzamides / pharmacology
  • Benzamides / therapeutic use*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Databases as Topic
  • Esophageal Neoplasms / drug therapy*
  • Esophageal Neoplasms / genetics
  • Esophageal Neoplasms / pathology
  • Esophageal Squamous Cell Carcinoma / drug therapy*
  • Esophageal Squamous Cell Carcinoma / genetics
  • Esophageal Squamous Cell Carcinoma / pathology
  • Gene Expression Regulation, Neoplastic / drug effects
  • Histone Deacetylase Inhibitors / pharmacology
  • Histone Deacetylase Inhibitors / therapeutic use*
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Oncogenes
  • Phenotype
  • RNA, Small Interfering / metabolism
  • Tensins / metabolism*

Substances

  • Benzamides
  • Histone Deacetylase Inhibitors
  • LMK-235
  • RNA, Small Interfering
  • TNS3 protein, human
  • Tensins