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

## TL;DR

This study shows that miR-146a reduces cancer cell growth and spread in non-small cell lung cancer by targeting sortilin-1.

## Contribution

The study identifies sortilin-1 as a direct target of miR-146a in NSCLC and demonstrates its functional role in tumor progression.

## Key findings

- SORT1 expression is significantly higher in NSCLC tissues compared to normal tissues.
- miR-146a suppresses SORT1, reducing NSCLC cell proliferation, migration, and invasion while promoting apoptosis.
- Dual-luciferase assays confirm that miR-146a directly targets SORT1 in NSCLC cells.

## Abstract

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.

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.

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.

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.

Immunohistochemistry revealed elevated sortilin‐1 expression in NSCLC patient tissues compared to adjacent normal tissue. In vitro, miR‐146a directly targeted and downregulated sortilin‐1 in NSCLC cell lines, as confirmed by dual‐luciferase reporter assay, qRT‐PCR, and Western blot. Silencing sortilin (via siRNA) or overexpressing miR‐146a (via mimic) significantly inhibited NSCLC cell proliferation (CCK‐8), migration (scratch/transwell), and invasion (transwell), while promot ed apoptosis (flow cytometry).