Hsa_circ_0049271 Facilitates Esophageal Squamous Cell Carcinoma Progression and Cisplatin Resistance by Enhancing Cellular Senescence via miR-455-5p/ETS1

Abstract

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.