ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Pharmacology of Anti-Cancer Drugs
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1605531
Dihydroartemisinin Targets the miR-497-5p/SOX5 Axis to Suppress Tumor Progression in Non-Small Cell Lung Cancer
Provisionally accepted
Qinghua Yin*
Qiang ZhouJian-Bing HuJie WengEr-Dong ShenFang WenSong-Lian LiuLei- Lan YinYa-Jun TongLing LongKe-Wei TangSi-Te BaiLu-Di Ou- Yueyang Central Hospital, Yueyang, China
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Non-small cell lung cancer (NSCLC) remains a lethal malignancy with limited therapeutic options. Dihydroartemisinin (DHA) exhibits anticancer properties, but 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, DHA (50 μM) significantly suppressed proliferation, migration, and invasion while inducing apoptosis in A549 and H1299 cells. Mechanistically, DHA upregulated tumor-suppressive miR-497-5p and downregulated its target SOX5, an oncogene overexpressed in clinical NSCLC specimens. Silencing miR-497-5p attenuated DHA's antitumor effects and increased SOX5 expression, whereas SOX5 knockdown reversed the phenotypic impact of miR-497-5p inhibition. In vivo, DHA (25/50 mg/kg) dose-dependently inhibited A549 xenograft tumor growth in mice, concomitant with miR-497-5p elevation and SOX5 suppression-effects abrogated by miR-497-5p inhibition but rescued by concurrent SOX5 knockdown. Collectively, these results demonstrate that DHA exerts antitumor activity by activating the miR-497-5p/SOX5 axis, revealing a novel molecular mechanism; however, bridging the gap between efficacious in vitro concentrations and clinically achievable dosing remains essential for future therapeutic translation.
Keywords: Dihydroartemisinin (DHA), Non-small cell lung cancer (NSCLC), miR-497-5p, SOX5, Anticancer activity
Received: 03 Apr 2025; Accepted: 25 Jun 2025.
Copyright: © 2025 Yin, Zhou, Hu, Weng, Shen, Wen, Liu, Yin, Tong, Long, Tang, Bai and Ou. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Qinghua Yin, Yueyang Central Hospital, Yueyang, China
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