Astragaloside IV suppresses development of hepatocellular carcinoma by regulating miR-150-5p/β-catenin axis.

Abstract

Hepatocellular carcinoma (HCC), a common malignant tumor, has been regarded as a leading cause of cancer-related deaths globally. Astragaloside IV (AS-IV) was reported to participate in the regulation of multiple tumors. However, the role of AS-IV in HCC was still unclear in HCC. Bioinformatics analysis and function or mechanism experiments including RT-qPCR, MTT assay, flow cytometry, Western blot, luciferase reporter assay and xenografts assays were applied to investigate the function of AS-IV, miR-150-5p and CTNNB1. We discovered that AS-IV treatment was supposed to significantly increase miR-150-5p level. In addition, AS-IV accelerated cell apoptosis by inducing miR-150-5p in vitro and in vivo. Furthermore, AS-IV increased cell apoptosis rate through reducing β-catenin level in vitro and in vivo. In detail, AS-IV triggered a decline of Bax and a rise of Bcl-2 in HCC cells and xenograft tissues. In mechanism, we validated the combination between miR-150-5p and CTNNB1. Moreover, miR-150-5p could negatively regulate CTNNB1 level by binding to its3'UTR. Finally, rescue assay demonstrated that CTNNB1 overexpression partially rescued the inhibitive effect on tumor growth and promotive influence on cell apoptosis caused by miR-150-5p amplification. The up-regulation of miR-150-5p induced by AS-IV suppressed the progression of HCC by repressing β-catenin, providing a new molecular target for the utilization of AS-IV In the treatment of HCC.

• Authors: Xiang Cui, Xiaoyan Jiang, Chunshan Wei, Yufeng Xing, Guangdong Tong
• Journal: Environmental toxicology and pharmacology (Environ Toxicol Pharmacol) Vol. 78 Pg. 103397 (Aug 2020) ISSN: 1872-7077 [Electronic] Netherlands
• PMID: 32417721 (Publication Type: Journal Article)
• Copyright: Copyright © 2020 Elsevier B.V. All rights reserved.

Chemical References

• Antineoplastic Agents, Phytogenic
• CTNNB1 protein, human
• MIRN150 microRNA, human
• MicroRNAs
• Saponins
• Triterpenes
• beta Catenin
• astragaloside A

Topics

• Animals
• Antineoplastic Agents, Phytogenic (pharmacology, therapeutic use)
• Apoptosis (drug effects)
• Carcinoma, Hepatocellular (drug therapy, genetics, metabolism)
• Cell Line, Tumor
• Humans
• Liver Neoplasms (drug therapy, genetics, metabolism)
• Male
• Mice, Inbred BALB C
• Mice, Nude
• MicroRNAs
• Saponins (pharmacology, therapeutic use)
• Triterpenes (pharmacology, therapeutic use)
• beta Catenin (genetics, metabolism)