HuR Affects Chemoresistance of Small Cell Lung Cancer by Regulating FGFRL1 Expression
Experimental and Therapeutic Medicine(2022)
摘要
Human antigen R (HuR), an RNA-binding protein, has been demonstrated to serve an oncogenic role in various types of cancer. Fibroblast growth factor receptor-like 1 (FGFRL1) has been shown to regulate small cell lung cancer (SCLC) chemoresistance. In the present study, the role of HuR in chemoresistance of SCLC, as well as its possible molecular mechanism involving FGFRL1, was explored by reverse transcription-quantitative PCR, western blotting, Cell Counting Kit-8 assay, flow cytometry and RNA immunoprecipitation. The results revealed that HuR expression levels were markedly upregulated in drug-resistant SCLC cell lines (H69AR and H446DDP) compared with in the parental cell lines (H69 and H446). Knockdown of HuR in drug-resistant SCLC cells enhanced drug sensitivity, cell apoptosis and cell cycle arrest. Furthermore, molecular mechanism studies indicated that HuR could bind and regulate FGFRL1 expression levels to increase FGFRL1 mRNA stability. Taken together, the present study suggested that HuR may mediate chemoresistance of SCLC by regulating FGFRL1 expression. HuR may represent a prognostic predictor and a potential target for overcoming chemoresistance in SCLC.
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关键词
human antigen R,small cell lung cancer,chemoresistance,fibroblast growth factor receptor-like 1
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