lncRNA MALAT1 participates in metformin inhibiting the proliferation of breast cancer cell.

Abstract

In recent years, the repurposing of conventional and chemotherapeutic drugs is recognized as an alternative strategy for health care. The main purpose of this study is to strengthen the application of non-oncological drug metformin on breast cancer treatment in the perspective of epigenetics. In the present study, metformin was found to inhibit cell proliferation, promote apoptosis and induce cell cycle arrest in breast cancer cells at a dose-dependent manner. In addition, metformin treatment elevated acH3K9 abundance and decreased acH3K18 level. The expression of lncRNA MALAT1, HOTAIR, DICER1-AS1, LINC01121 and TUG1 was up-regulated by metformin treatment. In metformin-treated cells, MALAT1 knock-down increased the Bax/Bcl2 ratio and enhanced p21 but decreased cyclin B1 expression. The expression of Beclin1, VDAC1, LC3-II, CHOP and Bip was promoted in the cells received combinatorial treatment of metformin and MALAT1 knock-down. The reduced phosphorylation of c-Myc was further decreased in the metformin-treated cells in combination with MALAT1 knock-down than metformin treatment alone. Taken together, these results provide a promising repurposed strategy for metformin on cancer treatment by modulating epigenetic modifiers.

• Authors: Yongye Huang, Ziyan Zhou, Jin Zhang, Zhenzhen Hao, Yunhao He, Zihan Wu, Yiquan Song, Kexun Yuan, Shanyu Zheng, Qi Zhao, Tianye Li, Bing Wang
• Journal: Journal of cellular and molecular medicine (J Cell Mol Med) Vol. 25 Issue 15 Pg. 7135-7145 (08 2021) ISSN: 1582-4934 [Electronic] England
• PMID: 34164906 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.

Chemical References

• Beclin-1
• Cyclin-Dependent Kinase Inhibitor p21
• DDIT3 protein, human
• Endoplasmic Reticulum Chaperone BiP
• Hypoglycemic Agents
• MALAT1 long non-coding RNA, human
• MAP1LC3B protein, human
• Microtubule-Associated Proteins
• RNA, Long Noncoding
• VDAC1 protein, human
• Transcription Factor CHOP
• Metformin
• Voltage-Dependent Anion Channel 1

Topics

• Apoptosis (drug effects)
• Beclin-1 (metabolism)
• Breast Neoplasms (metabolism)
• Cell Proliferation (drug effects)
• Cyclin-Dependent Kinase Inhibitor p21 (metabolism)
• Endoplasmic Reticulum Chaperone BiP (metabolism)
• Female
• Humans
• Hypoglycemic Agents (pharmacology)
• MCF-7 Cells
• Metformin (pharmacology)
• Microtubule-Associated Proteins (metabolism)
• RNA, Long Noncoding (genetics, metabolism)
• Transcription Factor CHOP (metabolism)
• Voltage-Dependent Anion Channel 1 (metabolism)