Research Paper|Volume 13, Issue 11|pp 15336—15352

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

Yang Shi^1,², Zheng Xiang⁴, Huiyu Yang^1,², Suliman Khan⁵, Ruizhe Li³, Siran Zhou^1,², Saif Ullah^1,², Jiyu Zhang^1,², Bingrong Liu^1,²

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

* Equal contribution

Received: February 2, 2021Accepted: March 6, 2021Published: May 28, 2021

https://doi.org/10.18632/aging.203091

Copyright: © 2021 Shi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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.