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 The monofunctional platinum(II) complex, phenanthriplatin, acts by blocking transcription, but its regulatory effects on long-noncoding RNAs (lncRNAs) have not been elucidated relative to traditional platinum-based chemotherapeutics, e.g., cisplatin. Here, we treated A549 non-small cell lun...

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Autores principales: Jerry D. Monroe, Satya A. Moolani, Elvin N. Irihamye, Katheryn E. Lett, Michael D. Hebert, Yann Gibert, Michael E. Smith
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Publicado: Nature Portfolio 2021
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spelling oai:doaj.org-article:e55824703fa84bb4bb1566c8e9a7f0a82021-12-02T16:51:31ZCisplatin and phenanthriplatin modulate long-noncoding RNA expression in A549 and IMR90 cells revealing regulation of microRNAs, Wnt/β-catenin and TGF-β signaling10.1038/s41598-021-89911-z2045-2322https://doaj.org/article/e55824703fa84bb4bb1566c8e9a7f0a82021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-89911-zhttps://doaj.org/toc/2045-2322Abstract The monofunctional platinum(II) complex, phenanthriplatin, acts by blocking transcription, but its regulatory effects on long-noncoding RNAs (lncRNAs) have not been elucidated relative to traditional platinum-based chemotherapeutics, e.g., cisplatin. Here, we treated A549 non-small cell lung cancer and IMR90 lung fibroblast cells for 24 h with either cisplatin, phenanthriplatin or a solvent control, and then performed microarray analysis to identify regulated lncRNAs. RNA22 v2 microRNA software was subsequently used to identify microRNAs (miRNAs) that might be suppressed by the most regulated lncRNAs. We found that miR-25-5p, -30a-3p, -138-5p, -149-3p, -185-5p, -378j, -608, -650, -708-5p, -1253, -1254, -4458, and -4516, were predicted to target the cisplatin upregulated lncRNAs, IMMP2L-1, CBR3-1 and ATAD2B-5, and the phenanthriplatin downregulated lncRNAs, AGO2-1, COX7A1-2 and SLC26A3-1. Then, we used qRT-PCR to measure the expression of miR-25-5p, -378j, -4516 (A549) and miR-149-3p, -608, and -4458 (IMR90) to identify distinct signaling effects associated with cisplatin and phenanthriplatin. The signaling pathways associated with these miRNAs suggests that phenanthriplatin may modulate Wnt/β-catenin and TGF-β signaling through the MAPK/ERK and PTEN/AKT pathways differently than cisplatin. Further, as some of these miRNAs may be subject to dissimilar lncRNA targeting in A549 and IMR90 cells, the monofunctional complex may not cause toxicity in normal lung compared to cancer cells by acting through distinct lncRNA and miRNA networks.Jerry D. MonroeSatya A. MoolaniElvin N. IrihamyeKatheryn E. LettMichael D. HebertYann GibertMichael E. SmithNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Jerry D. Monroe
Satya A. Moolani
Elvin N. Irihamye
Katheryn E. Lett
Michael D. Hebert
Yann Gibert
Michael E. Smith
Cisplatin and phenanthriplatin modulate long-noncoding RNA expression in A549 and IMR90 cells revealing regulation of microRNAs, Wnt/β-catenin and TGF-β signaling
description Abstract The monofunctional platinum(II) complex, phenanthriplatin, acts by blocking transcription, but its regulatory effects on long-noncoding RNAs (lncRNAs) have not been elucidated relative to traditional platinum-based chemotherapeutics, e.g., cisplatin. Here, we treated A549 non-small cell lung cancer and IMR90 lung fibroblast cells for 24 h with either cisplatin, phenanthriplatin or a solvent control, and then performed microarray analysis to identify regulated lncRNAs. RNA22 v2 microRNA software was subsequently used to identify microRNAs (miRNAs) that might be suppressed by the most regulated lncRNAs. We found that miR-25-5p, -30a-3p, -138-5p, -149-3p, -185-5p, -378j, -608, -650, -708-5p, -1253, -1254, -4458, and -4516, were predicted to target the cisplatin upregulated lncRNAs, IMMP2L-1, CBR3-1 and ATAD2B-5, and the phenanthriplatin downregulated lncRNAs, AGO2-1, COX7A1-2 and SLC26A3-1. Then, we used qRT-PCR to measure the expression of miR-25-5p, -378j, -4516 (A549) and miR-149-3p, -608, and -4458 (IMR90) to identify distinct signaling effects associated with cisplatin and phenanthriplatin. The signaling pathways associated with these miRNAs suggests that phenanthriplatin may modulate Wnt/β-catenin and TGF-β signaling through the MAPK/ERK and PTEN/AKT pathways differently than cisplatin. Further, as some of these miRNAs may be subject to dissimilar lncRNA targeting in A549 and IMR90 cells, the monofunctional complex may not cause toxicity in normal lung compared to cancer cells by acting through distinct lncRNA and miRNA networks.
format article
author Jerry D. Monroe
Satya A. Moolani
Elvin N. Irihamye
Katheryn E. Lett
Michael D. Hebert
Yann Gibert
Michael E. Smith
author_facet Jerry D. Monroe
Satya A. Moolani
Elvin N. Irihamye
Katheryn E. Lett
Michael D. Hebert
Yann Gibert
Michael E. Smith
author_sort Jerry D. Monroe
title Cisplatin and phenanthriplatin modulate long-noncoding RNA expression in A549 and IMR90 cells revealing regulation of microRNAs, Wnt/β-catenin and TGF-β signaling
title_short Cisplatin and phenanthriplatin modulate long-noncoding RNA expression in A549 and IMR90 cells revealing regulation of microRNAs, Wnt/β-catenin and TGF-β signaling
title_full Cisplatin and phenanthriplatin modulate long-noncoding RNA expression in A549 and IMR90 cells revealing regulation of microRNAs, Wnt/β-catenin and TGF-β signaling
title_fullStr Cisplatin and phenanthriplatin modulate long-noncoding RNA expression in A549 and IMR90 cells revealing regulation of microRNAs, Wnt/β-catenin and TGF-β signaling
title_full_unstemmed Cisplatin and phenanthriplatin modulate long-noncoding RNA expression in A549 and IMR90 cells revealing regulation of microRNAs, Wnt/β-catenin and TGF-β signaling
title_sort cisplatin and phenanthriplatin modulate long-noncoding rna expression in a549 and imr90 cells revealing regulation of micrornas, wnt/β-catenin and tgf-β signaling
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/e55824703fa84bb4bb1566c8e9a7f0a8
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