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

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

IntroductionNon-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 mediatin...

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Main Authors: Qing-Hua Yin, Qiang Zhou, Jian-Bing Hu, Jie Weng, Er-Dong Shen, Fang Wen, Song-Lian Liu, Lei-Lan Yin, Ya-Jun Tong, Ling Long, Ke-Wei Tang, Si-Te Bai, Lu-Di Ou
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-07-01
Series:Frontiers in Pharmacology
Subjects:
dihydroartemisinin (DHA)
non-small cell lung cancer (NSCLC)
miR-497-5p
SOX5
anticancer activity
Online Access:https://www.frontiersin.org/articles/10.3389/fphar.2025.1605531/full
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Summary:IntroductionNon-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.MethodsIn 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).ResultsDHA 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.DiscussionDHA 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.
ISSN:1663-9812

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