Circ_0074027 regulates the progression of non-small cell lung cancer via miR-1304-5p/GJB2 axis

• Published in: Molecular & cellular toxicology 2023, 19(1), , pp.41-52
• Main Authors: Zhang, Jie, Zhu, Yangli, Lin, Ya, Hu, Yuli, Kuang, Zhijian
• Format: Article
• Language: English
• Subjects: Apoptosis; BAX protein; Bcl-2 protein; Biomedical and Life Sciences; Cell Biology; Cell proliferation; Circular RNA; Flow cytometry; Immunoprecipitation; Life Sciences; Lung cancer; miRNA; Non-small cell lung carcinoma; Original Article; Pharmacology/Toxicology; Polymerase chain reaction; Small cell lung carcinoma; Thymidine; Tumors; Xenografts; 생물학
• ISSN: 1738-642X; 2092-8467
• DOI: 10.1007/s13273-022-00235-z

Background Non-small cell lung cancer (NSCLC) is one of the most common malignant tumors; circular RNA (circRNA) has been shown to be involved in the advance of NSCLC. However, the function of circ_0074027 in NSCLC has not been fully studied. Objective Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression of circ_0074027, microRNA-1304-5p (miR-1304-5p) and gap junction protein beta 2 (GJB2) in NSCLC. Cell counting kit-8 assay, thymidine analog 5-ethynyl-2′-deoxyuridine (EdU) assay, transwell assay, and flow cytometry were designed to explore cell function. Western blot examined the protein levels of Bax, Bcl-2 and GJB2. The relationship between miR-1304-5p and circ_0074027 or GJB2 was verified by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. The xenotransplantation model was established to study the role of circ_0074027 in vivo. Results circ_0074027 and GJB2 are significantly high-expressed in NSCLC tissues and cells. Silencing circ_0074027 reduced the proliferation, migration and invasion of NSCLC cells, and promoted cell apoptosis. MiR-1304-5p is a target of circ_0074027. Silencing circ_0074027 inhibited the malignant behavior of NSCLC cells by releasing miR-1304-5p. In addition, GJB2 is a target of miR-1304-5p. Overexpression of GJB2 partially restored the inhibitory effect of miR-1304-5p on cell malignant behavior. Animal experiments confirmed the anti-tumor effect of silence circ_0074027 in vivo. Conclusion Circ_0074027 regulates the expression of GJB2 by regulating miR-1304-5p, thereby promoting the development of NSCLC. Our study provides a novel targeted therapy for NSCLC.