HuR affects chemoresistance of small-cell lung cancer by regulating FGFRL1 expression

Human antigen R (HuR), an RNA-binding protein, has been found to play an oncogenic role in various cancers. Our previous study showed that fibroblast growth factor receptor-like 1 (FGFRL1) can regulate SCLC chemoresistance. In this research, we explored the role of HuR in chemoresistance of SCLC, as well as its possible molecular mechanism involving FGFRL1. We found that HuR expression was significantly up-regulated in drug-resistant SCLC cells (H69AR and H446DDP) compared with its parental cells (H69 and H446). Knockdown of HuR in drug-resistant SCLC cells enhanced drug sensitivity, cell apoptosis, and cell cycle arrest. Mechanistic investigations indicated that HuR could regulate FGFRL1 expression by interacting with it to increase its mRNA stability. Taken together, our results suggested that HuR medicated chemoresistance of SCLC by regulating FGFRL1 expression. HuR may represent a prognostic predictor and a potential target for overcoming chemoresistance in SCLC.