Exploring the Impact of hsa_circ_0049168 on NSCLC Proliferation and Apoptosis via the miR-370/PIN1 Regulatory Network

Abstract In this study, we explored the biological role and underlying mechanisms of hsa_circ_0049168 in NSCLC. Utilizing circRNA microarray analysis and bioinformatics analyzation, we identified a significant upregulation of hsa_circ_0049168 in both NSCLC tissues and cell lines. Our results demonstrate that hsa_circ_0049168, originating from the PIN1 gene, promotes tumor cell proliferation and inhibits apoptosis. Mechanistically, hsa_circ_0049168 functions by sponging miR-370, subsequently upregulating PIN1 expression, a key regulator of cellular proliferation and survival pathways. Through in vitro and in vivo experiments, we confirmed that knockdown of hsa_circ_0049168 leads to increased apoptosis and decreased proliferation of NSCLC cells. Moreover, the effects of hsa_circ_0049168 knockdown were reversed upon inhibition of miR-370, highlighting the specificity of the hsa_circ_0049168/miR-370/PIN1 regulatory axis in NSCLC. Notably, hsa_circ_0049168 was found to modulate key downstream targets, including β-catenin and cyclin D1, which play critical roles in cell cycle regulation and tumorigenesis. The clinical relevance of hsa_circ_0049168 was further underscored by its correlation with advanced tumor characteristics such as larger tumor size, poorer differentiation, and lymph node metastasis in NSCLC patients. Taken together, our findings suggest that hsa_circ_0049168 contributes to NSCLC progression via the miR-370/PIN1 axis and could serve as a promising biomarker for diagnosis and prognosis, as well as a potential therapeutic target in NSCLC.