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Article: Integrated mRNA and microRNA transcriptome sequencing characterizes sequence variants and mRNA – microRNA regulatory network in nasopharyngeal carcinoma model systems

TitleIntegrated mRNA and microRNA transcriptome sequencing characterizes sequence variants and mRNA – microRNA regulatory network in nasopharyngeal carcinoma model systems
Authors
Issue Date2014
PublisherElsevier BV. The Journal's web site is located at http://www.journals.elsevier.com/febs-open-bio
Citation
FEBS Open Bio, 2014, v. 4, p. 128-140 How to Cite?
AbstractNasopharyngeal carcinoma (NPC) is a prevalent malignancy in Southeast Asia among the Chinese population. Aberrant regulation of transcripts has been implicated in many types of cancers including NPC. Herein, we characterized mRNA and miRNA transcriptomes by RNA sequencing (RNASeq) of NPC model systems. Matched total mRNA and small RNA of undifferentiated Epstein-Barr virus (EBV)-positive NPC xenograft X666 and its derived cell line C666, well-differentiated NPC cell line HK1, and the immortalized nasopharyngeal epithelial cell line NP460 were sequenced by Solexa technology. We found 2812 genes and 149 miRNAs (human and EBV) to be differentially expressed in NP460, HK1, C666 and X666 with RNASeq; 533 miRNA-mRNA target pairs were inversely regulated in the three NPC cell lines compared to NP460. Integrated mRNA/miRNA expression profiling and pathway analysis show extracellular matrix organization, Beta-1 integrin cell surface interactions, and the PI3K/AKT, EGFR, ErbB, and Wnt pathways were potentially deregulated in NPC. Real-time quantitative PCR was performed on selected mRNA/miRNAs in order to validate their expression. Transcript sequence variants such as short insertions and deletions (INDEL), single nucleotide variant (SNV), and isomiRs were characterized in the NPC model systems. A novel TP53 transcript variant was identified in NP460, HK1, and C666. Detection of three previously reported novel EBV-encoded BART miRNAs and their isomiRs were also observed. Meta-analysis of a model system to a clinical system aids the choice of different cell lines in NPC studies. This comprehensive characterization of mRNA and miRNA transcriptomes in NPC cell lines and the xenograft provides insights on miRNA regulation of mRNA and valuable resources on transcript variation and regulation in NPC, which are potentially useful for mechanistic and preclinical studies. © 2014 The Authors.
Persistent Identifierhttp://hdl.handle.net/10722/198007
ISSN
2015 Impact Factor: 2.101
2015 SCImago Journal Rankings: 0.981
PubMed Central ID
ISI Accession Number ID
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DC FieldValueLanguage
dc.contributor.authorSzeto, CYYen_US
dc.contributor.authorLin, Cen_US
dc.contributor.authorChoi, SCen_US
dc.contributor.authorYip, TTen_US
dc.contributor.authorNgan, RKen_US
dc.contributor.authorTsao, GSWen_US
dc.contributor.authorLung, MLen_US
dc.date.accessioned2014-06-25T02:39:04Z-
dc.date.available2014-06-25T02:39:04Z-
dc.date.issued2014en_US
dc.identifier.citationFEBS Open Bio, 2014, v. 4, p. 128-140en_US
dc.identifier.issn2211-5463-
dc.identifier.urihttp://hdl.handle.net/10722/198007-
dc.description.abstractNasopharyngeal carcinoma (NPC) is a prevalent malignancy in Southeast Asia among the Chinese population. Aberrant regulation of transcripts has been implicated in many types of cancers including NPC. Herein, we characterized mRNA and miRNA transcriptomes by RNA sequencing (RNASeq) of NPC model systems. Matched total mRNA and small RNA of undifferentiated Epstein-Barr virus (EBV)-positive NPC xenograft X666 and its derived cell line C666, well-differentiated NPC cell line HK1, and the immortalized nasopharyngeal epithelial cell line NP460 were sequenced by Solexa technology. We found 2812 genes and 149 miRNAs (human and EBV) to be differentially expressed in NP460, HK1, C666 and X666 with RNASeq; 533 miRNA-mRNA target pairs were inversely regulated in the three NPC cell lines compared to NP460. Integrated mRNA/miRNA expression profiling and pathway analysis show extracellular matrix organization, Beta-1 integrin cell surface interactions, and the PI3K/AKT, EGFR, ErbB, and Wnt pathways were potentially deregulated in NPC. Real-time quantitative PCR was performed on selected mRNA/miRNAs in order to validate their expression. Transcript sequence variants such as short insertions and deletions (INDEL), single nucleotide variant (SNV), and isomiRs were characterized in the NPC model systems. A novel TP53 transcript variant was identified in NP460, HK1, and C666. Detection of three previously reported novel EBV-encoded BART miRNAs and their isomiRs were also observed. Meta-analysis of a model system to a clinical system aids the choice of different cell lines in NPC studies. This comprehensive characterization of mRNA and miRNA transcriptomes in NPC cell lines and the xenograft provides insights on miRNA regulation of mRNA and valuable resources on transcript variation and regulation in NPC, which are potentially useful for mechanistic and preclinical studies. © 2014 The Authors.-
dc.languageengen_US
dc.publisherElsevier BV. The Journal's web site is located at http://www.journals.elsevier.com/febs-open-bio-
dc.relation.ispartofFEBS Open Bioen_US
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.titleIntegrated mRNA and microRNA transcriptome sequencing characterizes sequence variants and mRNA – microRNA regulatory network in nasopharyngeal carcinoma model systemsen_US
dc.typeArticleen_US
dc.identifier.emailSzeto, CYY: cyyszeto@hku.hken_US
dc.identifier.emailLin, C: nicklin@hku.hken_US
dc.identifier.emailChoi, SC: scchoi66@hku.hken_US
dc.identifier.emailTsao, GSW: gswtsao@hku.hken_US
dc.identifier.emailLung, ML: mlilung@hku.hken_US
dc.identifier.authorityTsao, GSW=rp00399en_US
dc.identifier.authorityLung, ML=rp00300en_US
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1016/j.fob.2014.01.004-
dc.identifier.pmid24490137-
dc.identifier.pmcidPMC3907684-
dc.identifier.scopuseid_2-s2.0-84892876422-
dc.identifier.hkuros229532en_US
dc.identifier.volume10en_US
dc.identifier.spage128en_US
dc.identifier.epage140en_US
dc.identifier.isiWOS:000346278200016-
dc.relation.projectCentre for Nasopharyngeal Carcinoma Research-

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