Duan Xun-Huang, Chen Rui, Li Dao-Sheng, Luo Ai-Hua, Guo Lin-Lang
Department of Oncology, Jiujiang No. 1 People's Hospital, Jiujiang, Jiangxi 332000, P.R. China.
Department of Pathology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510220, P.R. China.
Exp Ther Med. 2022 Aug 24;24(4):638. doi: 10.3892/etm.2022.11575. eCollection 2022 Oct.
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.
人抗原R（HuR）是一种RNA结合蛋白，已被证明在多种类型的癌症中发挥致癌作用。成纤维细胞生长因子受体样1（FGFRL1）已被证明可调节小细胞肺癌（SCLC）的化疗耐药性。在本研究中，通过逆转录定量PCR、蛋白质免疫印迹法、细胞计数试剂盒-8检测、流式细胞术和RNA免疫沉淀，探讨了HuR在SCLC化疗耐药中的作用及其涉及FGFRL1的可能分子机制。结果显示，与亲本细胞系（H69和H446）相比，耐药SCLC细胞系（H69AR和H446DDP）中HuR的表达水平明显上调。在耐药SCLC细胞中敲低HuR可增强药物敏感性、细胞凋亡和细胞周期阻滞。此外，分子机制研究表明，HuR可结合并调节FGFRL1的表达水平，以增加FGFRL1 mRNA的稳定性。综上所述，本研究表明HuR可能通过调节FGFRL1的表达来介导SCLC的化疗耐药性。HuR可能是一种预后预测指标，也是克服SCLC化疗耐药性的潜在靶点。
