Identification of Targets of JS-K Against HBV-positive Human Hepatocellular Carcinoma HepG2.2.15 Cells with ITRAQ Proteomics

Overview

Journal Sci Rep

Specialty Science

Date 2021 May 18

PMID 34001947

Citations 5

Authors

Zhengyun Liu

Yan Xu

Wanling Zhang

Xinghong Gao

Guo Luo

Hong Song

Jie Liu

Huan Wang

Affiliations

Soon will be listed here.

Abstract

JS-K, a nitric oxide-releasing diazeniumdiolates, is effective against various tumors. We have discovered that JS-K was effective against Hepatitis B virus (HBV)-positive HepG2.2.15 cells. This study used iTRAQ to identify differentially expressed proteins following JS-K treatment of HepG2.2.15 cells. Silenced Transgelin (shTAGLN-2.15) cells were constructed, and the cell viability was analyzed by the CCK8 assay after treatment with JS-K. There were 182 differentially expressed proteins in JS-K treated-HepG2.2.15 cells; 73 proteins were up-regulated and 109 proteins were down-regulated. These proteins were categorized according to GO classification. KEGG enrichment analysis showed that Endocytosis, Phagosome and Proteoglycans were the most significant pathways. RT-PCR confirmed that the expression levels of TAGLN, IGFBP1, SMTN, SERPINE1, ANXA3, TMSB10, LGALS1 and KRT19 were significantly up-regulated, and the expression levels of C5, RBP4, CHKA, SIRT5 and TRIM14 were significantly down-regulated in JS-K treated-HepG2.2.15 cells. Western blotting confirmed the increased levels of USP13 and TAGLN proteins in JS-K treated-HepG2.2.15 cells. Molecular docking revealed the binding of JS-K to TAGLN and shTAGLN-2.15 cells were resistant to JS-K cytotoxicity, suggesting that TAGLN could be an important target in JS-K anti-HBV-positive liver cancer cells. These proteomic findings could shed new insights into mechanisms underlying the effect of JS-K against HBV-related HCC.

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