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
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Online Access:https://www.frontiersin.org/articles/10.3389/fphar.2025.1605531/full
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author 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
author_facet 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
author_sort Qing-Hua Yin
collection DOAJ
description 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.
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spelling doaj-art-5b2e3fdcb8234a55a0612c5ea3eb93152025-08-20T03:33:27ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-07-011610.3389/fphar.2025.16055311605531Dihydroartemisinin targets the miR-497-5p/SOX5 axis to suppress tumor progression in non-small cell lung cancerQing-Hua YinQiang ZhouJian-Bing HuJie WengEr-Dong ShenFang WenSong-Lian LiuLei-Lan YinYa-Jun TongLing LongKe-Wei TangSi-Te BaiLu-Di OuIntroductionNon-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.https://www.frontiersin.org/articles/10.3389/fphar.2025.1605531/fulldihydroartemisinin (DHA)non-small cell lung cancer (NSCLC)miR-497-5pSOX5anticancer activity
spellingShingle 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
Dihydroartemisinin targets the miR-497-5p/SOX5 axis to suppress tumor progression in non-small cell lung cancer
Frontiers in Pharmacology
dihydroartemisinin (DHA)
non-small cell lung cancer (NSCLC)
miR-497-5p
SOX5
anticancer activity
title Dihydroartemisinin targets the miR-497-5p/SOX5 axis to suppress tumor progression in non-small cell lung cancer
title_full Dihydroartemisinin targets the miR-497-5p/SOX5 axis to suppress tumor progression in non-small cell lung cancer
title_fullStr Dihydroartemisinin targets the miR-497-5p/SOX5 axis to suppress tumor progression in non-small cell lung cancer
title_full_unstemmed Dihydroartemisinin targets the miR-497-5p/SOX5 axis to suppress tumor progression in non-small cell lung cancer
title_short Dihydroartemisinin targets the miR-497-5p/SOX5 axis to suppress tumor progression in non-small cell lung cancer
title_sort dihydroartemisinin targets the mir 497 5p sox5 axis to suppress tumor progression in non small cell lung cancer
topic dihydroartemisinin (DHA)
non-small cell lung cancer (NSCLC)
miR-497-5p
SOX5
anticancer activity
url https://www.frontiersin.org/articles/10.3389/fphar.2025.1605531/full
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