Circular RNA hsa_circ_0004396 acts as a sponge of miR‐615‐5p to promote non‐small cell lung cancer progression and radioresistance through the upregulation of P21‐Activated Kinase 1

• Published in: Journal of clinical laboratory analysis 2022-06, Vol.36 (6), p.e24463-n/a
• Main Authors: Li, Dong, Yan, Lin, Zhang, Junhan, Gu, Feng
• Format: Article
• Language: English
• Subjects: Antibodies; Apoptosis; Bax protein; Bcl-x protein; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - radiotherapy; Cell cycle; Cell growth; Cell migration; Cell Proliferation - genetics; Cholecystokinin; circRNA hsa_circ_0004396; Circular RNA; Cloning; Cyclin-dependent kinase inhibitor p21; Flow cytometry; Gene expression; Humans; Kinases; Lung cancer; Lung Neoplasms - drug therapy; Lung Neoplasms - genetics; Lung Neoplasms - radiotherapy; Medical prognosis; MicroRNAs - genetics; MicroRNAs - metabolism; miR‐615‐5p; Non-small cell lung carcinoma; non‐small cell lung cancer; p21-Activated Kinases - genetics; p21-Activated Kinases - metabolism; PAK1; Proteins; Proto-Oncogene Proteins c-bcl-2 - metabolism; Radioresistance; Radiosensitivity; Reverse transcription; RNA, Circular - genetics; Small cell lung carcinoma; Therapeutic targets; Tumors; Up-Regulation - genetics; Xenografts
• ISSN: 0887-8013; 1098-2825
• DOI: 10.1002/jcla.24463

Backgrounds CircRNA hsa_circ_0004396 has been confirmed to be upregulated in human non‐small cell lung cancer (NSCLC). The aim of his study was to evaluate its mechanism in the radioresistance and progression of NSCLC. Methods Hsa_circ_0004396, miR‐615‐5p, and P21‐Activated Kinase 1 (PAK1) were measured by reverse transcription quantitative real‐time polymerase chain reaction (RT‐qPCR). The binding between miR‐615‐5p and hsa_circ_0004396 or PAK1 was predicted by circinteractome or Targetscan, as verified by dual‐luciferase reporter assay and RIP assay. Proliferation, clonogenicity capacity, cell cycle progression, apoptosis, migration, and invasion were assessed by CCK‐8, colony formation, flow cytometry, and Transwell assay. Bcl‐2, Bcl‐2 associated protein X (Bax), MMP‐2, and PAK1 protein levels were detected using western blot assay. In addition, in vivo function of hsa_circ_0004396 was evaluated by tumor xenograft assay. Results Hsa_circ_0004396 and PAK1 levels were upregulated, while miR‐615‐5p was declined in NSCLC. Hsa_circ_0004396 silencing inhibited NSCLC cell malignant behavior and induced radiosensitivity. Hsa_circ_0004396 functions as a molecular sponge of miR‐615‐5p to regulate PAK1 expression. Moreover, hsa_circ_0004396 knockdown inhibited NSCLC tumor growth in vivo. Conclusion Our findings demonstrated that hsa_circ_0004396 promoted NSCLC development and radioresistance through the miR‐615‐5p/PAK1 axis, which might provide a new therapeutic target for NSCLC treatment. CircHUWE1 boosted cell proliferation, radiosensitivity, migration and invasion and repressed apoptosis of NSCLC cells by regulating the miR‐615‐5p/PAK1 axis.