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

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.