Metformin may induce ferroptosis by inhibiting autophagy via lncRNA H19 in breast cancer

• Published in: FEBS open bio Vol. 12; no. 1; pp. 146 - 153
• Main Authors: Chen, Jida, Qin, Chuan, Zhou, Yulu, Chen, Yongxia, Mao, Misha, Yang, Jingjing
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01.01.2022; John Wiley and Sons Inc; Wiley
• Subjects: Apoptosis; Autophagy; Autophagy - genetics; biomedical research; Breast cancer; breast neoplasms; Breast Neoplasms - drug therapy; Breast Neoplasms - genetics; Cancer therapies; carcinogenesis; Cell culture; Female; Ferroptosis; Ferroptosis - genetics; H19; Humans; Lipids; Mammals; Medical research; Metformin; Metformin - pharmacology; Non-coding RNA; Protein expression; Proteins; Reactive oxygen species; RNA, Long Noncoding - genetics; Tumorigenesis; Tumors; United States > US; H19; breast cancer; metformin; autophagy; ferroptosis
• ISSN: 2211-5463; 2211-5463
• DOI: 10.1002/2211-5463.13314

Autophagy and ferroptosis have been major foci of biomedical research in recent years. Elucidation of their intrinsic molecular relationships is important for cancer prevention and treatment. Metformin can directly inhibit tumorigenesis, although the mechanism responsible for this is not fully understood. Here, we demonstrate that metformin and lncRNA‐H19 can regulate both autophagy and ferroptosis. Autophagy inducers and H19 can reverse the production of lipid reactive oxygen species and the inhibition of autophagy induced by metformin. The present study suggests that metformin may induce ferroptosis by inhibiting autophagy via H19, and this discovery may facilitate the development of novel therapies for the treatment of breast cancer. The present study demonstrates that metformin can inhibit autophagy and induce ferroptosis, and this can be reversed by H19. Furthermore, the induction of ferroptosis by knockdown of H19 can be reversed by inducing autophagy. These results imply that metformin may induce ferroptosis by inhibiting autophagy through H19, which further highlights the role of H19 in the anticancer effect of metformin.