Abstract
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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Acknowledgements
We would like to thank all the patients and family members participating in this work for their cooperation and patience. This study was supported by The First People’s Hospital of Wenling.
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JZ: formal analysis, methodology, data curation, and writing–review and editing. YZ and YL: conceptualization, data curation, and resourse. YH and ZK: methodology, software, and conceptualization.
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Jie Zhang declares that he has no conflict of interest. Yangli Zhu declares that she has no conflict of interest. Ya Lin declares that she has no conflict of interest. Yuli Hu declares that she has no conflict of interest. Zhijian Kuang declares that he has no conflict of interest.
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The research related to human use has been complied with all the relevant national regulations, and in accordance the tenets of the Helsinki Declaration, and has been approved by the Ethics Committee of The First People’s Hospital of Wenling.
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13273_2022_235_MOESM1_ESM.tif
Supplementary Fig. 1 The transfection efficiency of si-circ_0074027#1/#2/#3. After transfection with si-circ_0074027#1/#2/#3 into A549 and H1299 cells, circ_0074027 expression was detected by qRT-PCR. *P<0.05 (TIF 202 KB)
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Zhang, J., Zhu, Y., Lin, Y. et al. Circ_0074027 regulates the progression of non-small cell lung cancer via miR-1304-5p/GJB2 axis. Mol. Cell. Toxicol. 19, 41–52 (2023). https://doi.org/10.1007/s13273-022-00235-z
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DOI: https://doi.org/10.1007/s13273-022-00235-z