# Dihydroartemisinin targets the miR-497-5p/SOX5 axis to suppress tumor progression in non-small cell lung cancer

## TL;DR

This study shows that dihydroartemisinin fights non-small cell lung cancer by targeting a specific genetic pathway involving miR-497-5p and SOX5.

## Contribution

The paper identifies a novel mechanism by which dihydroartemisinin suppresses tumor progression via the miR-497-5p/SOX5 axis in NSCLC.

## Key findings

- DHA inhibits cancer cell proliferation, migration, and invasion while inducing apoptosis in NSCLC cells.
- DHA activates miR-497-5p and suppresses SOX5, a key driver in NSCLC progression.
- In vivo, DHA reduces tumor growth through the miR-497-5p/SOX5 axis, with effects confirmed by genetic manipulation.

## Abstract

Non-small cell lung cancer (NSCLC) remains a lethal malignancy with limited therapeutic options. Although dihydroartemisinin (DHA) exhibits anticancer properties, its mechanisms in NSCLC are incompletely understood. This study investigated the role of the miR-497-5p/SOX5 axis in mediating DHA’s effects on NSCLC.

In vitro experiments utilized A549 and H1299 cells treated with DHA (50 μM). Proliferation, migration, invasion, and apoptosis were assessed. miR-497-5p and SOX5 expression was modulated via genetic silencing. In vivo, A549 xenograft tumor growth in mice was evaluated under DHA treatment (25/50 mg/kg).

DHA significantly suppressed proliferation, migration, and invasion while inducing apoptosis in vitro. Mechanistically, DHA upregulated miR-497-5p and downregulated SOX5—overexpressed in clinical NSCLC. Silencing miR-497-5p attenuated DHA’s effects and increased SOX5, whereas SOX5 knockdown reversed miR-497-5p inhibition. In vivo, DHA dose-dependently inhibited tumor growth with miR-497-5p elevation and SOX5 suppression, effects abrogated by miR-497-5p inhibition but rescued by SOX5 knockdown.

DHA exerts antitumor activity by activating the miR-497-5p/SOX5 axis, revealing a novel mechanism. Bridging efficacious in vitro concentrations with clinically achievable dosing remains essential for therapeutic translation.