Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Ohtsuka, M; Ling, H; Ivan, C; Pichler, M; Matsushita, D; Goblirsch, M; Stiegelbauer, V; Shigeyasu, K; Zhang, X; Chen, M; Vidhu, F; Bartholomeusz, GA; Toiyama, Y; Kusunoki, M; Doki, Y; Mori, M; Song, S; Gunther, JR; Krishnan, S; Slaby, O; Goel, A; Ajani, JA; Radovich, M; Calin, GA.
H19 Noncoding RNA, an Independent Prognostic Factor, Regulates Essential Rb-E2F and CDK8-β-Catenin Signaling in Colorectal Cancer.
EBioMedicine. 2016; 13(3):113-124
Doi: 10.1016/j.ebiom.2016.10.026
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- Co-Autor*innen der Med Uni Graz
- Pichler Martin
- Stiegelbauer Verena
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- Abstract:
- The clinical significance of long noncoding RNAs (lncRNAs) in colorectal cancer (CRC) remains largely unexplored. Here, we analyzed a large panel of lncRNA candidates with The Cancer Genome Atlas (TCGA) CRC dataset, and identified H19 as the most significant lncRNA associated with CRC patient survival. We further validated such association in two independent CRC cohorts. H19 silencing blocked G1-S transition, reduced cell proliferation, and inhibited cell migration. We profiled gene expression changes to gain mechanism insight of H19 function. Transcriptome data analysis revealed not only previously identified mechanisms such as Let-7 regulation by H19, but also RB1-E2F1 function and β-catenin activity as essential upstream regulators mediating H19 function. Our experimental data showed that H19 affects phosphorylation of RB1 protein by regulating gene expression of CDK4 and CCND1. We further demonstrated that reduced CDK8 expression underlies changes of β-catenin activity, and identified that H19 interacts with macroH2A, an essential regulator of CDK8 gene transcription. However, the relevance of H19-macroH2A interaction in CDK8 regulation remains to be experimentally determined. We further explored the clinical relevance of above mechanisms in clinical samples, and showed that combined analysis of H19 with its targets improved prognostic value of H19 in CRC. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Cell Line, Tumor -
- Colorectal Neoplasms - genetics
- Colorectal Neoplasms - metabolism
- Colorectal Neoplasms - mortality
- Colorectal Neoplasms - pathology
- Cyclin-Dependent Kinase 8 - genetics
- Cyclin-Dependent Kinase 8 - metabolism
- Databases, Nucleic Acid -
- E2F Transcription Factors - metabolism
- Gene Expression Profiling -
- Gene Expression Regulation, Neoplastic -
- Gene Regulatory Networks -
- Humans -
- Mice -
- Prognosis -
- RNA Interference -
- RNA, Long Noncoding - genetics
- Retinoblastoma Protein - metabolism
- Signal Transduction -
- Survival Analysis -
- Transcriptome -
- beta Catenin - metabolism
- Find related publications in this database (Keywords)
- H19
- RB1
- E2F
- CDK8
- beta-Catenin
- Colorectal cancer