Arsenic trioxide inhibits EMT in hepatocellular carcinoma by promoting lncRNA MEG3 via PKM2.

Abstract

Hepatocellular carcinoma (HCC) presents a great burden for patients worldwide, and metastasis of HCC remains problematic. Arsenic trioxide is a traditional drug that has shown excellent efficacy when applied as cancer therapy. Our study explored the antimetastatic mechanism of arsenic trioxide in HCC. We investigated changes in pyruvate kinase muscle isoform 2 (PKM2) and maternal expression gene 3 (MEG3) following treatment with arsenic trioxide in HCC cells. Consequently, arsenic trioxide negatively regulated PKM2 and positively regulated MEG3. We explored migration ability and the expression of the epithelial to mesenchymal transition (EMT)-related biomarkers E-cadherin, N-cadherin and Vimentin by silencing MEG3 under arsenic trioxide treatment. The wound healing assay showed that arsenic trioxide inhibited the migration of HCC, but silencing MEG3 partially reversed this effect. On the other hand, the EMT-related biomarkers are alleviated under the treatment of arsenic trioxide, but this effect deteriorated when MEG3 is silenced. In conclusion, our study demonstrates a novel mechanism by which arsenic trioxide inhibits EMT in hepatocellular carcinoma by promoting lncRNA MEG3 and PKM2 negatively regulating MEG3.

• Authors: Zhuoyang Fan, Jing He, Tong Fu, Wei Zhang, Guowei Yang, Xudong Qu, Rong Liu, Lei Lv, Jianhua Wang
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 513 Issue 4 Pg. 834-840 (06 11 2019) ISSN: 1090-2104 [Electronic] United States
• PMID: 31003765 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019 Elsevier Inc. All rights reserved.

Chemical References

• Carrier Proteins
• MEG3 non-coding RNA, human
• Membrane Proteins
• RNA, Long Noncoding
• Thyroid Hormones
• Arsenic Trioxide

Topics

• Arsenic Trioxide (pharmacology)
• Carcinoma, Hepatocellular (drug therapy, pathology)
• Carrier Proteins (drug effects, metabolism)
• Cell Movement (drug effects)
• Epithelial-Mesenchymal Transition (drug effects)
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• Liver Neoplasms (drug therapy, pathology)
• Membrane Proteins (drug effects, metabolism)
• RNA, Long Noncoding (drug effects)
• Thyroid Hormones (metabolism)
• Tumor Cells, Cultured
• Thyroid Hormone-Binding Proteins