MicroRNA-dependent regulation of transcription in non-small cell lung cancer
Squamous cell lung cancer (SCC) and adenocarcinoma are the most common histological subtypes of non-small cell lung cancer (NSCLC), and have been traditionally managed in the clinic as a single entity. Increasing evidence, however, illustrates the biological diversity of these two histological subgr...
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| Veröffentlicht in: | PloS one 2014-03, Vol.9 (3), p.e90524-e90524 |
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| creator | Molina-Pinelo, Sonia Gutiérrez, Gabriel Pastor, Maria Dolores Hergueta, Marta Moreno-Bueno, Gema García-Carbonero, Rocío Nogal, Ana Suárez, Rocío Salinas, Ana Pozo-Rodríguez, Francisco Lopez-Rios, Fernando Agulló-Ortuño, Maria Teresa Ferrer, Irene Perpiñá, Asunción Palacios, José Carnero, Amancio Paz-Ares, Luis |
| description | Squamous cell lung cancer (SCC) and adenocarcinoma are the most common histological subtypes of non-small cell lung cancer (NSCLC), and have been traditionally managed in the clinic as a single entity. Increasing evidence, however, illustrates the biological diversity of these two histological subgroups of lung cancer, and supports the need to improve our understanding of the molecular basis beyond the different phenotypes if we aim to develop more specific and individualized targeted therapy. The purpose of this study was to identify microRNA (miRNA)-dependent transcriptional regulation differences between SCC and adenocarcinoma histological lung cancer subtypes. In this work, paired miRNA (667 miRNAs by TaqMan Low Density Arrays (TLDA)) and mRNA profiling (Whole Genome 44 K array G112A, Agilent) was performed in tumor samples of 44 NSCLC patients. Nine miRNAs and 56 mRNAs were found to be differentially expressed in SCC versus adenocarcinoma samples. Eleven of these 56 mRNA were predicted as targets of the miRNAs identified to be differently expressed in these two histological conditions. Of them, 6 miRNAs (miR-149, miR-205, miR-375, miR-378, miR-422a and miR-708) and 9 target genes (CEACAM6, CGN, CLDN3, ABCC3, MLPH, ACSL5, TMEM45B, MUC1) were validated by quantitative PCR in an independent cohort of 41 lung cancer patients. Furthermore, the inverse correlation between mRNAs and microRNAs expression was also validated. These results suggest miRNA-dependent transcriptional regulation differences play an important role in determining key hallmarks of NSCLC, and may provide new biomarkers for personalized treatment strategies. |
| doi_str_mv | 10.1371/journal.pone.0090524 |
| format | Article |
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Increasing evidence, however, illustrates the biological diversity of these two histological subgroups of lung cancer, and supports the need to improve our understanding of the molecular basis beyond the different phenotypes if we aim to develop more specific and individualized targeted therapy. The purpose of this study was to identify microRNA (miRNA)-dependent transcriptional regulation differences between SCC and adenocarcinoma histological lung cancer subtypes. In this work, paired miRNA (667 miRNAs by TaqMan Low Density Arrays (TLDA)) and mRNA profiling (Whole Genome 44 K array G112A, Agilent) was performed in tumor samples of 44 NSCLC patients. Nine miRNAs and 56 mRNAs were found to be differentially expressed in SCC versus adenocarcinoma samples. Eleven of these 56 mRNA were predicted as targets of the miRNAs identified to be differently expressed in these two histological conditions. Of them, 6 miRNAs (miR-149, miR-205, miR-375, miR-378, miR-422a and miR-708) and 9 target genes (CEACAM6, CGN, CLDN3, ABCC3, MLPH, ACSL5, TMEM45B, MUC1) were validated by quantitative PCR in an independent cohort of 41 lung cancer patients. Furthermore, the inverse correlation between mRNAs and microRNAs expression was also validated. These results suggest miRNA-dependent transcriptional regulation differences play an important role in determining key hallmarks of NSCLC, and may provide new biomarkers for personalized treatment strategies.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0090524</identifier><identifier>PMID: 24625834</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>3' Untranslated Regions ; Adenocarcinoma ; Adenocarcinoma - genetics ; Adenocarcinoma - metabolism ; Aged ; Biochemistry ; Biodiversity ; Biology ; Biomarkers ; Biomarkers, Tumor - metabolism ; Breast cancer ; Cancer ; Carcinoma, Non-Small-Cell Lung - genetics ; Carcinoma, Non-Small-Cell Lung - metabolism ; Carcinoma, Squamous Cell - genetics ; Carcinoma, Squamous Cell - metabolism ; Cohort Studies ; Female ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Gene regulation ; Genes ; Genes, Reporter ; Genome, Human ; Genomes ; Genomics ; Hospitals ; Humans ; Kinases ; Lung cancer ; Lung diseases ; Lung Neoplasms - genetics ; Lung Neoplasms - metabolism ; Male ; Medical prognosis ; Medicine ; MicroRNA ; MicroRNAs - metabolism ; Middle Aged ; miRNA ; Mucins ; Mutation ; Non-small cell lung cancer ; Non-small cell lung carcinoma ; Oncology ; Pathology ; Patients ; Polymerase Chain Reaction ; Ribonucleic acid ; RNA ; Small cell lung cancer ; Subgroups ; Target recognition ; Transcription ; Transcription (Genetics) ; Transcription, Genetic</subject><ispartof>PloS one, 2014-03, Vol.9 (3), p.e90524-e90524</ispartof><rights>COPYRIGHT 2014 Public Library of Science</rights><rights>2014 Molina-Pinelo et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2014 Molina-Pinelo et al 2014 Molina-Pinelo et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-d8781e4aa35d8264081ae7c9abbc19e7b1844c6dc92f93a06830c946864f7e3f3</citedby><cites>FETCH-LOGICAL-c692t-d8781e4aa35d8264081ae7c9abbc19e7b1844c6dc92f93a06830c946864f7e3f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3953115/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3953115/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79343,79344</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24625834$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Mari, Bernard</contributor><creatorcontrib>Molina-Pinelo, Sonia</creatorcontrib><creatorcontrib>Gutiérrez, Gabriel</creatorcontrib><creatorcontrib>Pastor, Maria Dolores</creatorcontrib><creatorcontrib>Hergueta, Marta</creatorcontrib><creatorcontrib>Moreno-Bueno, Gema</creatorcontrib><creatorcontrib>García-Carbonero, Rocío</creatorcontrib><creatorcontrib>Nogal, Ana</creatorcontrib><creatorcontrib>Suárez, Rocío</creatorcontrib><creatorcontrib>Salinas, Ana</creatorcontrib><creatorcontrib>Pozo-Rodríguez, Francisco</creatorcontrib><creatorcontrib>Lopez-Rios, Fernando</creatorcontrib><creatorcontrib>Agulló-Ortuño, Maria Teresa</creatorcontrib><creatorcontrib>Ferrer, Irene</creatorcontrib><creatorcontrib>Perpiñá, Asunción</creatorcontrib><creatorcontrib>Palacios, José</creatorcontrib><creatorcontrib>Carnero, Amancio</creatorcontrib><creatorcontrib>Paz-Ares, Luis</creatorcontrib><title>MicroRNA-dependent regulation of transcription in non-small cell lung cancer</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Squamous cell lung cancer (SCC) and adenocarcinoma are the most common histological subtypes of non-small cell lung cancer (NSCLC), and have been traditionally managed in the clinic as a single entity. Increasing evidence, however, illustrates the biological diversity of these two histological subgroups of lung cancer, and supports the need to improve our understanding of the molecular basis beyond the different phenotypes if we aim to develop more specific and individualized targeted therapy. The purpose of this study was to identify microRNA (miRNA)-dependent transcriptional regulation differences between SCC and adenocarcinoma histological lung cancer subtypes. In this work, paired miRNA (667 miRNAs by TaqMan Low Density Arrays (TLDA)) and mRNA profiling (Whole Genome 44 K array G112A, Agilent) was performed in tumor samples of 44 NSCLC patients. Nine miRNAs and 56 mRNAs were found to be differentially expressed in SCC versus adenocarcinoma samples. Eleven of these 56 mRNA were predicted as targets of the miRNAs identified to be differently expressed in these two histological conditions. Of them, 6 miRNAs (miR-149, miR-205, miR-375, miR-378, miR-422a and miR-708) and 9 target genes (CEACAM6, CGN, CLDN3, ABCC3, MLPH, ACSL5, TMEM45B, MUC1) were validated by quantitative PCR in an independent cohort of 41 lung cancer patients. Furthermore, the inverse correlation between mRNAs and microRNAs expression was also validated. 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Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Molina-Pinelo, Sonia</au><au>Gutiérrez, Gabriel</au><au>Pastor, Maria Dolores</au><au>Hergueta, Marta</au><au>Moreno-Bueno, Gema</au><au>García-Carbonero, Rocío</au><au>Nogal, Ana</au><au>Suárez, Rocío</au><au>Salinas, Ana</au><au>Pozo-Rodríguez, Francisco</au><au>Lopez-Rios, Fernando</au><au>Agulló-Ortuño, Maria Teresa</au><au>Ferrer, Irene</au><au>Perpiñá, Asunción</au><au>Palacios, José</au><au>Carnero, Amancio</au><au>Paz-Ares, Luis</au><au>Mari, Bernard</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>MicroRNA-dependent regulation of transcription in non-small cell lung cancer</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2014-03-13</date><risdate>2014</risdate><volume>9</volume><issue>3</issue><spage>e90524</spage><epage>e90524</epage><pages>e90524-e90524</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Squamous cell lung cancer (SCC) and adenocarcinoma are the most common histological subtypes of non-small cell lung cancer (NSCLC), and have been traditionally managed in the clinic as a single entity. Increasing evidence, however, illustrates the biological diversity of these two histological subgroups of lung cancer, and supports the need to improve our understanding of the molecular basis beyond the different phenotypes if we aim to develop more specific and individualized targeted therapy. The purpose of this study was to identify microRNA (miRNA)-dependent transcriptional regulation differences between SCC and adenocarcinoma histological lung cancer subtypes. In this work, paired miRNA (667 miRNAs by TaqMan Low Density Arrays (TLDA)) and mRNA profiling (Whole Genome 44 K array G112A, Agilent) was performed in tumor samples of 44 NSCLC patients. Nine miRNAs and 56 mRNAs were found to be differentially expressed in SCC versus adenocarcinoma samples. Eleven of these 56 mRNA were predicted as targets of the miRNAs identified to be differently expressed in these two histological conditions. Of them, 6 miRNAs (miR-149, miR-205, miR-375, miR-378, miR-422a and miR-708) and 9 target genes (CEACAM6, CGN, CLDN3, ABCC3, MLPH, ACSL5, TMEM45B, MUC1) were validated by quantitative PCR in an independent cohort of 41 lung cancer patients. Furthermore, the inverse correlation between mRNAs and microRNAs expression was also validated. These results suggest miRNA-dependent transcriptional regulation differences play an important role in determining key hallmarks of NSCLC, and may provide new biomarkers for personalized treatment strategies.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>24625834</pmid><doi>10.1371/journal.pone.0090524</doi><tpages>e90524</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2014-03, Vol.9 (3), p.e90524-e90524 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1507247036 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Free Full-Text Journals in Chemistry; Public Library of Science (PLoS) |
| subjects | 3' Untranslated Regions Adenocarcinoma Adenocarcinoma - genetics Adenocarcinoma - metabolism Aged Biochemistry Biodiversity Biology Biomarkers Biomarkers, Tumor - metabolism Breast cancer Cancer Carcinoma, Non-Small-Cell Lung - genetics Carcinoma, Non-Small-Cell Lung - metabolism Carcinoma, Squamous Cell - genetics Carcinoma, Squamous Cell - metabolism Cohort Studies Female Gene Expression Profiling Gene Expression Regulation, Neoplastic Gene regulation Genes Genes, Reporter Genome, Human Genomes Genomics Hospitals Humans Kinases Lung cancer Lung diseases Lung Neoplasms - genetics Lung Neoplasms - metabolism Male Medical prognosis Medicine MicroRNA MicroRNAs - metabolism Middle Aged miRNA Mucins Mutation Non-small cell lung cancer Non-small cell lung carcinoma Oncology Pathology Patients Polymerase Chain Reaction Ribonucleic acid RNA Small cell lung cancer Subgroups Target recognition Transcription Transcription (Genetics) Transcription, Genetic |
| title | MicroRNA-dependent regulation of transcription in non-small cell lung cancer |
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