Biomedical Research Center and Key Laboratory of Biotherapy of Zhejiang Province, Hangzhou, China.
Department of Pathology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, China.
FEBS Open Bio. 2022 Jan;12(1):146-153. doi: 10.1002/2211-5463.13314. Epub 2021 Oct 27.
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.
自噬和铁死亡是近年来生物医学研究的主要焦点。阐明它们内在的分子关系对癌症的预防和治疗很重要。二甲双胍可以直接抑制肿瘤的发生,尽管其机制尚不完全清楚。在这里,我们证明二甲双胍和长链非编码 RNA-H19 可以调节自噬和铁死亡。自噬诱导物和 H19 可以逆转二甲双胍诱导的脂质活性氧的产生和自噬的抑制。本研究表明,二甲双胍可能通过 H19 抑制自噬诱导铁死亡,这一发现可能有助于开发治疗乳腺癌的新疗法。