MIR100HG promoted ferroptosis via regulating the expression of ACSL3 in lung cancer cells

Abstract

Abstract MIR100HG, a lncRNA residing on chromosome 11, affected the occurrence and prognosis of many cancers. Although previous reports revealed that MIR100HG was down-regulated in lung tumor tissues and prolonged the survival time of lung cancer patients, its detailed mechanism remained elusive. In our study, the mechanism of MIR100HG on ferroptosis in lung cancer cells was investigated. RT-PCR revealed that MIR100HG was upregulated by RSL3. Subsequently, MIR100HG was found to affect intracellular GSH and ROS levels and promote RSL3-induced ferroptosis in lung cancer cells. In vitro experiments, including transcriptomics sequencing, RT-PCR, western blot and RNA immunoprecipitation (RIP), found that MIR100HG was mainly located in the nucleus and negatively regulated the expression of ACSL3 via affecting the association of HuR and the mRNA of ACSL3. Analyzing RNA-sequencing data in TCGA database and measuring their expression levels unveiled that MIR100HG and ACSL3 were differentially expressed between lung cancer and paired-paracancerous tissues. Moreover, KM plotter results indicated that MIR100HG and ACSL3 affected the prognosis of lung cancer patients. Although still needing to be further investigated, our results showed that the MIR100HG-ACSL3 axis regulated ferroptosis in lung cancer cells and affected the occurrence and prognosis of lung cancer for the first time.