A significant difference was identified following in vitro experiments for the NSCLC cell line A549, which revealed that miR‑146a‑5p and TCSF regulated cell viability, proliferation and apoptosis.
Taken together, our work reveals that miR-146a-5p functions as a tumor suppressor in NSCLC by controlling various metabolic and signaling pathways through direct and indirect mechanisms.
Subsequently, MUC5AC, a major mucin in the human respiratory tract correlated with post-operative metastasis and recurrence of NSCLC, is confirmed to be regulated by SNHG16 and miR-146a, and plays a positive role in promoting cell proliferation, migration and invasion, which might be involved in the oncogenic activity of SNHG16-miR-146a axis in NSCLC.
In a CAM xenograft tumor model, overexpression of miR‑146a‑5p inhibited the tumorigenesis and angiogenesis of an NSCLC cell line. miR‑146a‑5p may act as a tumor suppressor gene in NSCLC and have moderate prognostic value in lung cancer.
Furthermore, siRNA-mediated downregulation of CCND1 or CCND2 yielded the same effects on proliferation and cell cycle arrest as miR-146a-5p upregulation did in the NSCLC cell lines.
The patients with high miR-146a expression in their tumors showed longer progression-free survival (25.6 weeks in miR-146a high patients vs. 4.8 weeks in miR-146a low patients, P<0.05). miR-146a is therefore a strong candidate prognostic biomarker in NSCLC.
Our findings suggest that polymorphisms in the rs2910164 of miR-146a and the rs11614913 of miR-196a2 are associated with prognosis in patients with completely resected NSCLC.
Our results seem to demonstrate that sequence variants of miR-196a2 can have an influence on its expression, while miR-146a can have a role in increasing the risk of NSCLC.