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

Abstract

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.

Current perspectives on naturally occurring saponins as anticancer agents

“…ZnS ( 17 , IC 50 : 0.51 and 1.0 µM, CCK‐8 assay), isolated from Dioscorea zingiberensis C. H. Wright, exhibited profound activity against Huh7 and SMMC‐7721 hepatocellular carcinoma cell lines. [ 30 ] ZnS significantly inhibited the viability, apoptosis, invasion, and tumorigenicity of hepatocellular carcinoma cells by regulating the expression of TCONS‐00026762. In the SMMC‐7721 xenograft mouse model, ZnS (60 mg/kg, oral administration) suppressed ~75% of the tumor volume without affecting body weight.…”

Zingiberensis Newsaponin Inhibits the Malignant Progression of Hepatocellular Carcinoma via Suppressing Autophagy Moderated by the AKR1C1-Mediated JAK2/STAT3 Pathway

“…Our previous study has shown that the anticancer activity of ZnS against HCC may be involved with the inhibition of autophagy [ 28 ]. Hence, the effects of 3-MA (a specific autophagy inhibitor) on HCC were simultaneously investigated in this study.…”

“…Wright. Some studies have demonstrated that ZnS exhibits antiproliferative, proapoptotic, and antimetastasis effects in cancer treatment [ 28 , 32 ]. Similarly, our study found that ZnS inhibited the viability and migration, as well as promoted the apoptosis of HCC cells.…”

“…Recently, autophagy has attracted considerable attention as a potential target of drugs for cancer treatment. Our previous study has suggested that the anticancer activity of ZnS may be associated with the inhibition of autophagy [ 28 ]. Therefore, the relationship between ZnS and autophagy was further investigated.…”

Zingiberensis New Saponin Inhibits LncRNA TCONS-00026762/AKR1C1 Pathway, Revealing Unique Insights into Cellular Processes and Drug Response in Hepatocellular Carcinoma

“…For example, in breast cancer, metformin induces ferroptosis by suppressing autophagy through the lncRNA H19 (11). Our previous study found that Zingiberensis new saponin (ZnS) inhibits HCC growth by downregulating the expression of a novel LncRNA TCONS-00026762 (12); however, the exact mechanism by which LncRNA TCONS-00026762 inhibits HCC growth is unclear.…”