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

Background: The etiology and carcinogenesis of hepatocellular carcinoma (HCC) are associated with various risk factors. Saponins extracted from Dioscorea zingiberensis C. H. Wright exhibit antitumor activity against HCC. This study aimed to investigate the effect and the underlying mechanism of Dios...

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Main Authors: Xing Liu, Pingsheng Zhou, Keqing He, Zhili Wen, Yong Gao
Format: Article
Language:English
Published: Frontiers Media S.A. 2021-05-01
Series:Frontiers in Pharmacology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fphar.2021.678620/full
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author Xing Liu
Xing Liu
Pingsheng Zhou
Keqing He
Zhili Wen
Yong Gao
author_facet Xing Liu
Xing Liu
Pingsheng Zhou
Keqing He
Zhili Wen
Yong Gao
author_sort Xing Liu
collection DOAJ
description Background: The etiology and carcinogenesis of hepatocellular carcinoma (HCC) are associated with various risk factors. Saponins extracted from Dioscorea zingiberensis C. H. Wright exhibit antitumor activity against HCC. This study aimed to investigate the effect and the underlying mechanism of Dioscorea Zingiberensis new saponin (ZnS) on HCC.Methods: Human HCC cell lines, Huh7 and SMMC-7721, were treated with different concentrations of ZnS. Cell apoptosis was determined via 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 in vivo. The expression of apoptosis-related proteins was detected in vivo and in vitro via western blotting.Results: 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 in vivo. Furthermore, ZnS and TCONS-00026762 regulated cell apoptotic pathways.Conclusion: 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.
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spelling doaj.art-7cdfc0425485497a86a88dd6f80f05582022-12-21T19:05:15ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122021-05-011210.3389/fphar.2021.678620678620Dioscorea Zingiberensis New Saponin Inhibits the Growth of Hepatocellular Carcinoma by Suppressing the Expression of Long Non-coding RNA TCONS-00026762Xing Liu0Xing Liu1Pingsheng Zhou2Keqing He3Zhili Wen4Yong Gao5Department of Oncology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, ChinaDepartment of Medicine, Jinggangshan University, Ji’an, ChinaInternational Education College, Jiangxi University of Traditional Chinese Medicine, Nanchang, ChinaDepartment of Hepatobiliary Diseases, Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine, Nanchang, ChinaDepartment of Gastroenterology, The Second Affiliated Hospital of Nanchang University, Nanchang, ChinaDepartment of Oncology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, ChinaBackground: The etiology and carcinogenesis of hepatocellular carcinoma (HCC) are associated with various risk factors. Saponins extracted from Dioscorea zingiberensis C. H. Wright exhibit antitumor activity against HCC. This study aimed to investigate the effect and the underlying mechanism of Dioscorea Zingiberensis new saponin (ZnS) on HCC.Methods: Human HCC cell lines, Huh7 and SMMC-7721, were treated with different concentrations of ZnS. Cell apoptosis was determined via 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 in vivo. The expression of apoptosis-related proteins was detected in vivo and in vitro via western blotting.Results: 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 in vivo. Furthermore, ZnS and TCONS-00026762 regulated cell apoptotic pathways.Conclusion: 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.https://www.frontiersin.org/articles/10.3389/fphar.2021.678620/fullHepatocellular carcinoma (HCC)long non-coding RNA (lncRNA)dioscorea zingiberensis new saponin (ZnS)TCONS-00026762apoptosis
spellingShingle Xing Liu
Xing Liu
Pingsheng Zhou
Keqing He
Zhili Wen
Yong Gao
Dioscorea Zingiberensis New Saponin Inhibits the Growth of Hepatocellular Carcinoma by Suppressing the Expression of Long Non-coding RNA TCONS-00026762
Frontiers in Pharmacology
Hepatocellular carcinoma (HCC)
long non-coding RNA (lncRNA)
dioscorea zingiberensis new saponin (ZnS)
TCONS-00026762
apoptosis
title Dioscorea Zingiberensis New Saponin Inhibits the Growth of Hepatocellular Carcinoma by Suppressing the Expression of Long Non-coding RNA TCONS-00026762
title_full Dioscorea Zingiberensis New Saponin Inhibits the Growth of Hepatocellular Carcinoma by Suppressing the Expression of Long Non-coding RNA TCONS-00026762
title_fullStr Dioscorea Zingiberensis New Saponin Inhibits the Growth of Hepatocellular Carcinoma by Suppressing the Expression of Long Non-coding RNA TCONS-00026762
title_full_unstemmed Dioscorea Zingiberensis New Saponin Inhibits the Growth of Hepatocellular Carcinoma by Suppressing the Expression of Long Non-coding RNA TCONS-00026762
title_short Dioscorea Zingiberensis New Saponin Inhibits the Growth of Hepatocellular Carcinoma by Suppressing the Expression of Long Non-coding RNA TCONS-00026762
title_sort dioscorea zingiberensis new saponin inhibits the growth of hepatocellular carcinoma by suppressing the expression of long non coding rna tcons 00026762
topic Hepatocellular carcinoma (HCC)
long non-coding RNA (lncRNA)
dioscorea zingiberensis new saponin (ZnS)
TCONS-00026762
apoptosis
url https://www.frontiersin.org/articles/10.3389/fphar.2021.678620/full
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