Circ_0010235 confers cisplatin resistance in lung cancer by upregulating E2F7 through absorbing miR‐379‐5p
Background Cisplatin (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 ca...
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Veröffentlicht in: | Thoracic cancer 2023-07, Vol.14 (20), p.1946-1957 |
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Zusammenfassung: | Background
Cisplatin (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.
Methods
Expression 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.
Results
Circ_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.
Conclusion
Circ_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.
Circ_0010235 elevates E2F7 expression by absorbing miR‐379‐5p, thereby promoting DDP resistance and tumor growth in lung cancer. |
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ISSN: | 1759-7706 1759-7714 |
DOI: | 10.1111/1759-7714.14941 |