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KMID : 1034820230190010041
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Molecular & Cellular Toxicology
2023 Volume.19 No. 1 p.41 ~ p.52
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Circ_0074027 regulates the progression of non-small cell lung cancer via miR-1304-5p/GJB2 axis
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Jie Zhang
Yangli Zhu
Ya Lin
Yuli Hu
Vivek Mohan Sharma
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Abstract
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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.
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KEYWORD
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Circ_0074027, MiR-1304-5p, GJB2, Non-small cell lung cancer
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