Exploring the Impact of hsa_circ_0049168 on Non-Small Cell Lung Cancer Proliferation and Apoptosis via the microRNA-370/PIN1 Regulatory Network

In this study, we investigated the biological role and underlying mechanisms of hsa_circ_0049168 in Non-Small Cell Lung Cancer (NSCLC). Using circular RNA (circRNA) microarray analysis and bioinformatics tools, 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 Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (pin1) gene, promotes tumor cell proliferation and inhibits apoptosis. Mechanistically, hsa_circ_0049168 functions by sponging miR-370, leading to the upregulation of PIN1 expression, a key regulator of cellular proliferation and survival pathways. In and ex vivo experiments confirmed that silencing hsa_circ_0049168 increased apoptosis and decreased proliferation in 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 also modulates key downstream targets such as β-catenin and cyclin D1, which are involved in cell cycle regulation and tumorigenesis. The clinical relevance of hsa_circ_0049168 was further confirmed by its correlation with advanced tumor characteristics, including larger tumor size, poorer differentiation, lymph node metastasis, and clinical stage in NSCLC patients. In conclusion, 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, prognosis, and potential therapeutic targeting in NSCLC.