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 Shi1,2, *, , Zheng Xiang4, *, , Huiyu Yang1,2, *, , Suliman Khan5, *, , Ruizhe Li3, , Siran Zhou1,2, , Saif Ullah1,2, , Jiyu Zhang1,2, , Bingrong Liu1,2, ,

  • 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, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
  • 4 Department of Pathology, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Henan University People's Hospital, Zhengzhou 450003, China
  • 5 Department of Cerebrovascular Diseases, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou 450000, China
* Equal contribution

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

https://doi.org/10.18632/aging.203091
How to Cite

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.

Abbreviations

DEGs: Differentially Expressed Genes; DMSO: Dimethyl sulfoxide; EAC: Esophageal Adenocarcinoma; EC: Esophageal cancer; EdU: 5-Ethynyl-2ยด-deoxyuridine; ESCC: Esophageal squamous cell cancer; FFPE: Formalin-fixed paraffin-embedded; FPKM: Normalized fragments per kilobase per million mapped reads; GDC: Genomic Data Commons; GEO: Gene Expression Omnibus; GI cancer: Gastrointestinal cancer; GO analysis: Gene Ontology analysis; GSEA: Gene Set Enrichment Analysis; GTEx: Genotype-Tissue Expression (GTEx) project; HATs: Histone acetyltransferases; HDACs: Histone deacetylases; HDACis: HDAC inhibitors; H3K9ac: Acetylated lysine 9 of histone 3; H3K14ac: Acetylated lysine 14 of histone 3; H3K27ac: Acetylated lysine 27 of histone 3; IC50: The half maximal inhibitory concentration; IF: Immunofluorescence; IHC: Immunohistochemistry; IRB: Institutional Review Board; KEGG: Kyoto Encyclopedia of Genes and Genomes; LOWESS: Locally weighted scatterplot smoothing; NC: Negative control; OD: Optical density; OS: Overall survival; real-time qRT-PCR: Real-time quantitative reverse transcription-polymerase chain reaction; RNA-seq: RNA-sequencing; RT: Room temperature; SEM: Standard error of the mean; SRA: Sequence Read Archive; TCGA: The Cancer Genome Atlas program; WCE: Whole-cell extraction.