Affiliation:
1. Department of Pulmonary and Critical Care Medicine Changzhou Third People's Hospital Changzhou China
2. Department of Pulmonary and Critical Care Medicine The Third Affiliated Hospital of Hebei Medical University Shijiazhuang China
Abstract
AbstractBackgroundCisplatin (DDP) treatment is one of the most predominant chemotherapeutic strategies for lung cancer patients. Circular RNAs (circRNAs) have been revealed to participate in the chemoresistance in lung cancer. Hence, the role and mechanism of circ_0010235 in cisplatin resistance in lung cancer was investigated.MethodsExpression levels of circ_0010235, microRNA (miR)‐379‐5p and E2F transcription factor 7 (E2F7) were analyzed using quantitative reverse transcription PCR (qRT‐PCR) and western blot. Cell DDP sensitivity, proliferation, apoptosis, invasion, and migration were detected by cell counting kit‐8 assay, 5‐ethynyl‐2′‐deoxyuridine (EDU) assay, flow cytometry and western blot, respectively. The binding interaction was verified using dual‐luciferase reporter assay. A murine xenograft model was established to investigate effects in vivo.ResultsCirc_0010235 was highly expressed in DDP‐resistant lung cancer tissues and cells. Knockdown of circ_0010235 elevated DDP sensitivity, constrained proliferation, invasion and migration as well as fostered apoptosis in DDP‐resistant lung cancer cells. Moreover, circ_0010235 silencing boosted DDP sensitivity and impeded tumor growth in lung cancer in vivo. Mechanistically, circ_0010235 acted as a sponge for miR‐379‐5p to elevate the expression of its target E2F7. Rescue experiments showed that miR‐379‐5p inhibition attenuated circ_0010235 knockdown‐evoked reduction on DDP resistance of DDP‐resistant cancer cells. In addition, miR‐379‐5p re‐expression elevated DDP sensitivity and suppressed the malignant phenotype of DDP‐resistant lung cancer cells through miR‐379‐5p.ConclusionCirc_0010235 knockdown reduced DDP resistance and tumor growth via miR‐379‐5p/ E2F7 axis in lung cancer, suggesting an effective therapeutic target for lung cancer patients.
Subject
Pulmonary and Respiratory Medicine,Oncology,General Medicine