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Cisplatin and phenanthriplatin modulate long-noncoding RNA expression in A549 and IMR90 cells revealing regulation of microRNAs, Wnt/β-catenin and TGF-β signaling

Abstract:
Lung cancer cells tend to develop resistance to cisplatin (DDP) during continuous chemotherapy, making it crucial to improve DDP sensitivity to enhance therapeutic outcomes. The levels of miR-149-3p in lung tissues and cells, as well as the biological behaviors of lung cancer cells, were analyzed. H446/DDP and A549/DDP cell lines were established to investigate how miR-149-3p affects lung cancer cells’ sensitivity to DDP. Bioinformatics analysis predicted transmembrane serine protease 4 (TMPRSS4) as a downstream target of miR-149-3p, which was subsequently confirmed. Western blot analysis was used to examine proteins related to migration, invasion, apoptosis, and TMPRSS4 expression. Additionally, a subcutaneous graft tumor model in nude mice was created to assess the impact of miR-149-3p on tumor growth. In lung cancer tissues and cells, miR-149-3p expression was reduced, while TMPRSS4 expression was elevated. Overexpression of miR-149-3p inhibited cancer progression, promoted apoptosis, and enhanced the chemosensitivity of lung cancer cells to DDP. Moreover, miR-149-3p negatively regulated TMPRSS4, reducing malignancy-associated characteristics of lung cancer cells and further improving their DDP sensitivity. In vivo, high miR-149-3p expression increased the chemosensitivity of cancer cells. In conclusion, miR-149-3p suppresses the aggressive progression of lung cancer by directly downregulating TMPRSS4 and enhances the responsiveness of lung cancer cells to DDP
Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.1038/s41598-021-89911-z

Authors

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Role:
Author
ORCID:
0000-0001-8543-5799
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Institution:
University of Oxford
Role:
Author
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Role:
Author
ORCID:
0000-0002-6233-9654



Publisher:
Nature Research
Journal:
Scientific Reports More from this journal
Volume:
11
Issue:
1
Pages:
10408-10408
Article number:
10408
Publication date:
2021-05-17
DOI:
EISSN:
2045-2322
ISSN:
2045-2322


Language:
English
Keywords:
Pubs id:
1621823
Local pid:
pubs:1621823
Source identifiers:
W3133233794
Deposit date:
2026-06-08
ARK identifier:
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