MicroRNA induction by copy number gain is associated with poor outcome in squamous cell carcinoma of the lung

Abstract Copy number gains in cancer genomes have been shown to induce oncogene expression and promote carcinogenesis; however, their role in regulating oncogenic microRNAs (onco-miRNAs) remains largely unknown. Our aim was to identify onco-miRNAs induced by copy number gains in human squamous cell...

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Autores principales: Endi Xia, Sotaro Kanematsu, Yusuke Suenaga, Asmaa Elzawahry, Hitomi Kondo, Noriko Otsuka, Yasumitsu Moriya, Toshihiko Iizasa, Mamoru Kato, Ichiro Yoshino, Sana Yokoi
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Publicado: Nature Portfolio 2018
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spelling oai:doaj.org-article:9e94e1852eac42cc81b1c053060701a02021-12-02T15:08:38ZMicroRNA induction by copy number gain is associated with poor outcome in squamous cell carcinoma of the lung10.1038/s41598-018-33696-12045-2322https://doaj.org/article/9e94e1852eac42cc81b1c053060701a02018-10-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-33696-1https://doaj.org/toc/2045-2322Abstract Copy number gains in cancer genomes have been shown to induce oncogene expression and promote carcinogenesis; however, their role in regulating oncogenic microRNAs (onco-miRNAs) remains largely unknown. Our aim was to identify onco-miRNAs induced by copy number gains in human squamous cell carcinoma (Sq) of the lung. We performed a genome-wide screen of onco-miRNAs from 245 Sqs using data sets from RNA-sequencing, comparative genomic hybridization, and the corresponding clinical information from The Cancer Genome Atlas. Among 1001 miRNAs expressed in the samples, 231 were correlated with copy number alternations, with only 11 of these being highly expressed in Sq compared to adenocarcinoma and normal tissues. Notably, miR-296-5p, miR-324-3p, and miR-3928-3p expression was significantly associated with poor prognosis. Multivariate analysis using the Cox proportional hazards model showed that miRNA expression and smoking were independent prognostic factors and were associated with poor prognosis. Furthermore, the three onco-miRNAs inhibited FAM46C to induce MYC expression, promoting proliferation of Sq cells. We found that copy number gains in Sq of the lung induce onco-miRNA expression that is associated with poor prognosis.Endi XiaSotaro KanematsuYusuke SuenagaAsmaa ElzawahryHitomi KondoNoriko OtsukaYasumitsu MoriyaToshihiko IizasaMamoru KatoIchiro YoshinoSana YokoiNature PortfolioarticleCopy Number AlternationsThe Cancer Genome Atlas (TCGA)Induce Oncogene ExpressionmiRNA Mimic TransfectionDifferentially Expressed miRNA (DEMI)MedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-10 (2018)
institution DOAJ
collection DOAJ
language EN
topic Copy Number Alternations
The Cancer Genome Atlas (TCGA)
Induce Oncogene Expression
miRNA Mimic Transfection
Differentially Expressed miRNA (DEMI)
Medicine
R
Science
Q
spellingShingle Copy Number Alternations
The Cancer Genome Atlas (TCGA)
Induce Oncogene Expression
miRNA Mimic Transfection
Differentially Expressed miRNA (DEMI)
Medicine
R
Science
Q
Endi Xia
Sotaro Kanematsu
Yusuke Suenaga
Asmaa Elzawahry
Hitomi Kondo
Noriko Otsuka
Yasumitsu Moriya
Toshihiko Iizasa
Mamoru Kato
Ichiro Yoshino
Sana Yokoi
MicroRNA induction by copy number gain is associated with poor outcome in squamous cell carcinoma of the lung
description Abstract Copy number gains in cancer genomes have been shown to induce oncogene expression and promote carcinogenesis; however, their role in regulating oncogenic microRNAs (onco-miRNAs) remains largely unknown. Our aim was to identify onco-miRNAs induced by copy number gains in human squamous cell carcinoma (Sq) of the lung. We performed a genome-wide screen of onco-miRNAs from 245 Sqs using data sets from RNA-sequencing, comparative genomic hybridization, and the corresponding clinical information from The Cancer Genome Atlas. Among 1001 miRNAs expressed in the samples, 231 were correlated with copy number alternations, with only 11 of these being highly expressed in Sq compared to adenocarcinoma and normal tissues. Notably, miR-296-5p, miR-324-3p, and miR-3928-3p expression was significantly associated with poor prognosis. Multivariate analysis using the Cox proportional hazards model showed that miRNA expression and smoking were independent prognostic factors and were associated with poor prognosis. Furthermore, the three onco-miRNAs inhibited FAM46C to induce MYC expression, promoting proliferation of Sq cells. We found that copy number gains in Sq of the lung induce onco-miRNA expression that is associated with poor prognosis.
format article
author Endi Xia
Sotaro Kanematsu
Yusuke Suenaga
Asmaa Elzawahry
Hitomi Kondo
Noriko Otsuka
Yasumitsu Moriya
Toshihiko Iizasa
Mamoru Kato
Ichiro Yoshino
Sana Yokoi
author_facet Endi Xia
Sotaro Kanematsu
Yusuke Suenaga
Asmaa Elzawahry
Hitomi Kondo
Noriko Otsuka
Yasumitsu Moriya
Toshihiko Iizasa
Mamoru Kato
Ichiro Yoshino
Sana Yokoi
author_sort Endi Xia
title MicroRNA induction by copy number gain is associated with poor outcome in squamous cell carcinoma of the lung
title_short MicroRNA induction by copy number gain is associated with poor outcome in squamous cell carcinoma of the lung
title_full MicroRNA induction by copy number gain is associated with poor outcome in squamous cell carcinoma of the lung
title_fullStr MicroRNA induction by copy number gain is associated with poor outcome in squamous cell carcinoma of the lung
title_full_unstemmed MicroRNA induction by copy number gain is associated with poor outcome in squamous cell carcinoma of the lung
title_sort microrna induction by copy number gain is associated with poor outcome in squamous cell carcinoma of the lung
publisher Nature Portfolio
publishDate 2018
url https://doaj.org/article/9e94e1852eac42cc81b1c053060701a0
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