Sortilin‐1, Targeted by miR‐146a, Regulates the Behavior of Non‐Small Cell Lung Cancer

Background Sortilin‐1 (SORT1) has been implicated in the pathogenesis of various malignancies, but its role in non‐small cell lung cancer (NSCLC) remains to be elucidated. Methods Immunohistochemistry was employed to assess the expression of SORT1 in cancerous tissues compared to adjacent non‐cancerous tissues. NSCLC cell lines, including A549, H1299, and PC‐9, underwent treatment with miR‐146a mimics or SORT1 small interfering RNA (siRNA), followed by evaluations of cell viability, migration, invasion, and apoptosis using cell counting kit‐8, transwell assays, and scratch wound assays. Additionally, bioinformatic methods were employed to predict miR‐146a target genes, which were subsequently validated through dual‐luciferase reporter assays. Results SORT1 was significantly elevated in NSCLC tissues compared to adjacent non‐cancerous counterparts. Downregulation of SORT1 inhibited proliferation, invasion, migration of tumor cell lines and promoted apoptosis. Moreover, SORT1 was a direct target of miR‐146a. MiR‐146a modulated tumor cell proliferation, migration, invasion, and apoptosis by suppressing SORT1 expression. Conclusion These results suggest that miR‐146a plays a critical role in the pathogenesis of NSCLC by targeting SORT1, highlighting its potential as a therapeutic target for NSCLC.