Bao Erwen, Li Shuai, Shen Peipei, Qian Danqi, Xu Yu, Zhou Jialiang
Department of Tumor Radiotherapy, Affiliated Hospital of Jiangnan University, Wuxi, China.
J Biochem Mol Toxicol. 2025 Jun;39(6):e70328. doi: 10.1002/jbt.70328.
Cisplatin resistance is a major therapeutic challenge in esophageal squamous cell carcinoma (ESCC). circRNAs play an important role in cisplatin resistance. The aim of this paper was to investigate the role and mechanism of hsa_circ_0049271 in ESCC progression and drug resistance. GEO database was retrieved to collect circRNAs, miRNAs, and mRNAs associated with cisplatin resistance in ESCC. Reverse transcription-quantitative PCR (RT-qPCR) was used to detect hsa_circ_0049271 expression levels in ESCC cell lines. CCK-8 assay, flow cytometric assay, and cell migration/invasion assays were used to examine the function of hsa_circ_0049271 in ESCC cells. RT-qPCR and coculture assays were used to detect the effect of circRNA_103615 on cellular senescence under cisplatin treatment. Hsa_circ_0049271, miR-455-5p, and ETS1 were dysregulated in ESCC tissues. ESCC cell lines had increased levels of hsa_circ_0049271 and ETS1 mRNA compared with normal cells and normal tissues, as well as decreased levels of miR-455-5p. Functionally, small interfering RNA silencing of hsa_circ_0049271 by small interfering RNA resulted in suppression of cell growth, migration, and invasion in both non-senescent and senescent cells. MiR-455-5p was significantly increased, but ETS1 expression was significantly decreased after hsa_circ_0049271 knockdown. Hsa_circ_0049271 promoted the secretion of senescence-associated secretory phenotypes, including IL1B, IL6, CXCL5, and MMP3. Hsa_circ_0049271 may enhance DDP treatment-induced cellular senescence to promote ESCC progression and chemoresistance through the miR-455-5p/ETS1 axis.
顺铂耐药是食管鳞状细胞癌（ESCC）治疗中的一项重大挑战。环状RNA（circRNAs）在顺铂耐药中发挥重要作用。本文旨在研究hsa_circ_0049271在ESCC进展和耐药中的作用及机制。检索基因表达综合数据库（GEO数据库）以收集与ESCC顺铂耐药相关的circRNAs、微小RNA（miRNAs）和信使核糖核酸（mRNAs）。采用逆转录定量聚合酶链反应（RT-qPCR）检测ESCC细胞系中hsa_circ_0049271的表达水平。采用细胞计数试剂盒-8（CCK-8）检测法、流式细胞术检测法及细胞迁移/侵袭检测法来研究hsa_circ_0049271在ESCC细胞中的功能。采用RT-qPCR和共培养检测法检测顺铂处理下circRNA_103615对细胞衰老的影响。hsa_circ_0049271、miR-455-5p和ETS1在ESCC组织中表达失调。与正常细胞和正常组织相比，ESCC细胞系中hsa_circ_0049271和ETS1 mRNA水平升高，而miR-455-5p水平降低。在功能上，通过小干扰RNA沉默hsa_circ_0049271可抑制非衰老细胞和衰老细胞的生长、迁移及侵袭。hsa_circ_0049271敲低后，miR-455-5p显著升高，但ETS1表达显著降低。hsa_circ_0049271促进衰老相关分泌表型的分泌，包括白细胞介素1β（IL1B）、白细胞介素6（IL6）、CXC趋化因子配体5（CXCL5）和基质金属蛋白酶3（MMP3）。hsa_circ_0049271可能通过miR-455-5p/ETS1轴增强顺铂治疗诱导的细胞衰老，从而促进ESCC进展和化疗耐药。
