Overexpression of LINC00551 promotes autophagy-dependent ferroptosis of lung adenocarcinoma via upregulating DDIT4 by sponging miR-4328
Xiong Peng, Rui Yang, Weilin Peng, Zhenyu Zhao, Guangxu Tu, Boxue He, Qidong Cai, Shuai Shi, Wei Yin, Fenglei Yu, Yongguang Tao, Xiang Wang
Abstract
According to mounting evidence, long noncoding RNAs (lncRNAs) play a vital role in regulated cell death (RCD). A potential strategy for cancer therapy involves triggering ferroptosis, a novel form of RCD. Although it is thought to be an autophagy-dependent process, it is still unclear how the two processes interact. This study characterized a long intergenic noncoding RNA, LINC00551, expressed at a low level in lung adenocarcinoma (LUAD) and some other cancers. Overexpression of LINC00551 suppresses cell viability while promoting autophagy and RSL-3-induced ferroptosis in LUAD cells. LINC00551 acts as a competing endogenous RNA (ceRNA) and binds with miR-4328 which up-regulates the target DNA damage-inducible transcript 4 (DDIT4). DDIT4 inhibits the activity of mTOR, promotes LUAD autophagy, and then promotes the ferroptosis of LUAD cells in an autophagy-dependent manner. This study provided an insight into the molecular mechanism regulating ferroptosis and highlighted LINC00551 as a potential therapeutic target for LUAD.