1. Academic Validation
  2. Pharmacological targeting of TNS3 with histone deacetylase inhibitor as a therapeutic strategy in esophageal squamous cell carcinoma

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.
Yang Shi 1 2 Zheng Xiang 3 Huiyu Yang 1 2 Suliman Khan 4 Ruizhe Li 5 Siran Zhou 1 2 Saif Ullah 1 2 Jiyu Zhang 1 2 Bingrong Liu 1 2
Affiliations

Affiliations

  • 1 Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
  • 2 State Key Laboratory of Esophageal Cancer Prevention and Treatment, Zhengzhou University, Zhengzhou 450052, China.
  • 3 Department of Pathology, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Henan University People's Hospital, Zhengzhou 450003, China.
  • 4 Department of Cerebrovascular Diseases, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou 450000, China.
  • 5 Department of Pathology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
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.

Figures
Products