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

组蛋白去乙酰化酶抑制剂对 TNS3 的药理靶向治疗作为食管鳞状细胞癌的治疗策略

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作者:Yang Shi, Zheng Xiang, Huiyu Yang, Suliman Khan, Ruizhe Li, Siran Zhou, Saif Ullah, Jiyu Zhang, Bingrong Liu

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.

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