MiR-143 enhances the antitumor activity of shikonin by targeting BAG3 expression in human glioblastoma stem cells.

Abstract

Therapeutic applications of microRNAs (miRNAs) in chemotherapy were confirmed to be valuable, but there is rare to identify their specific roles and functions in shikonin treatment toward tumors. Here, for the first time, we reported that miR-143 played a critical role in the antitumor activity of shikonin in glioblastoma stem cells (GSCs). The results showed that the expression of miR-143 was downregulated in shikonin treated GSCs within 24 h. MiR-143 overexpression significantly enhanced the inhibitory effect of shikonin toward GSCs on cell viability. Besides, miR-143 overexpression caused a significant increase in the apoptotic fraction and made apoptosis occur earlier. Further investigation identified that BAG3, an apoptotic regulator, was a functional target of miR-143 in shikonin treated GSCs. The expression of BAG3 was upregulated in shikonin treated GSCs within 24 h. MiR-143 overexpression significantly reversed the high expression of BAG3 in shikonin treated GSCs. Moreover, it was confirmed that the enhanced cytotoxicity of shikonin by miR-143 overexpression was reversed by BAG3 overexpression both in vitro and in vivo, suggesting that the enhanced tumor suppressive effects by miR-143 overexpression was at least partly through the regulation of BAG3. Taken together, for the first time, our results demonstrate that miR-143 could enhance the antitumor activity of shikonin toward GSCs through reducing BAG3 expression, which may provide a novel therapeutic strategy for enhancing the treatment efficacy of shikonin toward GSCs.

• Authors: Jing Liu, Cheng-Bin Qu, Yi-Xue Xue, Zhen Li, Ping Wang, Yun-hui Liu
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) 2015 Dec 4-11 Vol. 468 Issue 1-2 Pg. 105-12 ISSN: 1090-2104 [Electronic] United States
• PMID: 26541455 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Inc. All rights reserved.

Chemical References

• Adaptor Proteins, Signal Transducing
• Antineoplastic Agents, Phytogenic
• Apoptosis Regulatory Proteins
• BAG3 protein, human
• Drugs, Chinese Herbal
• MIRN143 microRNA, human
• MicroRNAs
• Naphthoquinones
• shikonin

Topics

• Adaptor Proteins, Signal Transducing (genetics)
• Animals
• Antineoplastic Agents, Phytogenic (therapeutic use)
• Apoptosis Regulatory Proteins (genetics)
• Down-Regulation (drug effects)
• Drugs, Chinese Herbal (therapeutic use)
• Gene Expression Regulation, Neoplastic (drug effects)
• Glioblastoma (drug therapy, genetics, pathology)
• Humans
• Male
• Mice, Nude
• MicroRNAs (genetics)
• Naphthoquinones (therapeutic use)
• Neoplastic Stem Cells (drug effects, metabolism, pathology)
• Tumor Cells, Cultured
• Up-Regulation (drug effects)