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Integrative CAGE and DNA Methylation Profiling Identify Epigenetically Regulated Genes in NSCLC
Univ Tokyo, Dept Resp Med, Grad Sch Med, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1130033, Japan.;Univ Tokyo, Div Hlth Serv Promot, Bunkyo Ku, Tokyo, Japan.;RIKEN Ctr Life Sci Technol, DGT, Yokohama, Kanagawa, Japan..
RIKEN Ctr Life Sci Technol, DGT, Yokohama, Kanagawa, Japan..
Ohu Univ, Dept Biochem, Sch Pharmaceut Sci, Koriyama, Fukushima, Japan..
Univ Tokyo, Dept Resp Med, Grad Sch Med, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1130033, Japan..
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2017 (English)In: Molecular Cancer Research, ISSN 1541-7786, E-ISSN 1557-3125, Vol. 15, no 10, p. 1354-1365Article in journal (Refereed) Published
Abstract [en]

Lung cancer is the leading cause of cancer-related deaths worldwide. The majority of cancer driver mutations have been identified; however, relevant epigenetic regulation involved in tumorigenesis has only been fragmentarily analyzed. Epigenetically regulated genes have a great theranostic potential, especially in tumors with no apparent driver mutations. Here, epigenetically regulated genes were identified in lung cancer by an integrative analysis of promoter-level expression profiles from Cap Analysis of Gene Expression (CAGE) of 16 nonsmall cell lung cancer (NSCLC) cell lines and 16 normal lung primary cell specimens with DNA methylation data of 69 NSCLC cell lines and 6 normal lung epithelial cells. A core set of 49 coding genes and 10 long noncoding RNAs (lncRNA), which are upregulated in NSCLC cell lines due to promoter hypomethylation, was uncovered. Twenty-two epigenetically regulated genes were validated (upregulated genes with hypomethylated promoters) in the adenocarcinoma and squamous cell cancer subtypes of lung cancer using The Cancer Genome Atlas data. Furthermore, it was demonstrated that multiple copies of the REP522 DNA repeat family are prominently upregulated due to hypomethylation in NSCLC cell lines, which leads to cancer-specific expression of lncRNAs, such as RP1-90G24.10, AL022344.4, and PCAT7. Finally, Myeloma Overexpressed (MYEOV) was identified as the most promising candidate. Functional studies demonstrated that MYEOV promotes cell proliferation, survival, and invasion. Moreover, high MYEOV expression levels were associated with poor prognosis. (C) 2017 AACR.

Place, publisher, year, edition, pages
AMER ASSOC CANCER RESEARCH , 2017. Vol. 15, no 10, p. 1354-1365
National Category
Cancer and Oncology
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URN: urn:nbn:se:uu:diva-337081DOI: 10.1158/1541-7786.MCR-17-0191ISI: 000412161400006PubMedID: 28698358OAI: oai:DiVA.org:uu-337081DiVA, id: diva2:1179377
Available from: 2018-02-01 Created: 2018-02-01 Last updated: 2018-02-01Bibliographically approved

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