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姜新皂苷通过抑制长链非编码RNA TCONS-00026762的表达来抑制肝细胞癌的生长。

Zingiberensis New Saponin Inhibits the Growth of Hepatocellular Carcinoma by Suppressing the Expression of Long Non-coding RNA TCONS-00026762.

作者信息

Liu Xing, Zhou Pingsheng, He Keqing, Wen Zhili, Gao Yong

机构信息

Department of Oncology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.

Department of Medicine, Jinggangshan University, Ji'an, China.

出版信息

Front Pharmacol. 2021 May 3;12:678620. doi: 10.3389/fphar.2021.678620. eCollection 2021.

Abstract

The etiology and carcinogenesis of hepatocellular carcinoma (HCC) are associated with various risk factors. Saponins extracted from zingiberensis C. H. Wright exhibit antitumor activity against HCC. This study aimed to investigate the effect and the underlying mechanism of Zingiberensis new saponin (ZnS) on HCC. Human HCC cell lines, Huh7 and SMMC-7721, were treated with different concentrations of ZnS. Cell apoptosis was determined flow cytometry assay. Differentially expressed lncRNAs (DElncRNAs) in ZnS-treated SMMC-7721 cells were determined through RNA-sequence. The role of lncRNA TCONS-00026762 in HCC was investigated gain of function analysis, along with cell proliferation, apoptosis, and invasion in HCC cells. A subcutaneous xenograft of SMMC-7721 cell lines was established to study the effects of TCONS-00026762 . The expression of apoptosis-related proteins was detected and western blotting. ZnS inhibited the proliferation of HCC cell in a dose-dependent manner. ZnS could induce apoptosis in HCC cells. Illumina sequencing results showed that 493 DElncRNAs were identified in ZnS-treated SMMC-7721 cells. TCONS-00026762 expression was down-regulated in the ZnS-treated SMMC-7721 cells. TCONS-00026762 inhibited the effect of ZnS on the proliferation, apoptosis, and invasion of HCC cells. ZnS inhibited the tumor growth, while, TCONS-00026762 promoted tumor growth . Furthermore, ZnS and TCONS-00026762 regulated cell apoptotic pathways. ZnS significantly inhibits the viability, apoptosis, invasion, and tumorigenicity of HCC cells by regulating the expression of TCONS-00026,762. Our findings provide novel insights into the potential role of lncRNA in HCC therapy.

摘要

肝细胞癌(HCC)的病因和致癌作用与多种危险因素相关。从温郁金中提取的皂苷对HCC具有抗肿瘤活性。本研究旨在探讨温郁金新皂苷(ZnS)对HCC的作用及其潜在机制。用不同浓度的ZnS处理人HCC细胞系Huh7和SMMC - 7721。通过流式细胞术检测细胞凋亡。通过RNA测序确定ZnS处理的SMMC - 7721细胞中差异表达的长链非编码RNA(DElncRNAs)。通过功能获得分析研究lncRNA TCONS - 00026762在HCC中的作用,以及其对HCC细胞增殖、凋亡和侵袭的影响。建立SMMC - 7721细胞系的皮下异种移植模型以研究TCONS - 00026762的作用。通过蛋白质免疫印迹法检测凋亡相关蛋白的表达。ZnS以剂量依赖性方式抑制HCC细胞的增殖。ZnS可诱导HCC细胞凋亡。Illumina测序结果显示,在ZnS处理的SMMC - 7721细胞中鉴定出493个DElncRNAs。在ZnS处理的SMMC - 7721细胞中,TCONS - 00026762的表达下调。TCONS - 00026762抑制了ZnS对HCC细胞增殖、凋亡和侵袭的作用。ZnS抑制肿瘤生长,而TCONS - 00026762促进肿瘤生长。此外,ZnS和TCONS - 00026762调节细胞凋亡途径。ZnS通过调节TCONS - 00026762的表达,显著抑制HCC细胞的活力、凋亡、侵袭和致瘤性。我们的研究结果为lncRNA在HCC治疗中的潜在作用提供了新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff63/8126712/8e7418439c56/fphar-12-678620-g001.jpg

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