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Article

Integrative In Silico and In Vitro Transcriptomics Analysis Revealed Gene Expression Changes and Oncogenic Features of Normal Cholangiocytes after Chronic Alcohol Exposure

1
Applied Biological Sciences Program, Chulabhorn Graduate Institute, Chulabhorn Royal Academy, Bangkok 10210, Thailand
2
Laboratory of Pharmacology, Chulabhorn Research Institute, Bangkok 10210, Thailand
3
Center of Excellence on Environmental Health and Toxicology, Office of Higher Education Commission, Ministry of Education, Bangkok 10400, Thailand
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(23), 5987; https://doi.org/10.3390/ijms20235987
Received: 23 October 2019 / Revised: 18 November 2019 / Accepted: 20 November 2019 / Published: 28 November 2019
(This article belongs to the Special Issue Cell Targets and Toxicity)
Cholangiocarcinoma (CCA) is a malignant tumor originating from cholangiocyte. Prolonged alcohol consumption has been suggested as a possible risk factor for CCA, but there is no information about alcohol’s mechanisms in cholangiocyte. This study was designed to investigate global transcriptional alterations through RNA-sequencing by using chronic alcohol exposure (20 mM for 2 months) in normal human cholangiocyte MMNK-1 cells. To observe the association of alcohol induced CCA pathogenesis, we combined differentially expressed genes (DEGs) with computational bioinformatics of CCA by using publicly gene expression omnibus (GEO) datasets. For biological function analysis, Gene ontology (GO) analysis showed biological process and molecular function related to regulation of transcription from RNA polymerase II promoter, while cellular component linked to the nucleoplasm. KEGG pathway presented pathways in cancer that were significantly enriched. From KEGG result, we further examined the oncogenic features resulting in chronic alcohol exposure, enhanced proliferation, and migration through CCND-1 and MMP-2 up-regulation, respectively. Finally, combined DEGs were validated in clinical data including TCGA and immunohistochemistry from HPA database, demonstrating that FOS up-regulation was related to CCA pathogenesis. This study is the first providing more information and molecular mechanisms about global transcriptome alterations and oncogenic enhancement of chronic alcohol exposure in normal cholangiocytes. View Full-Text
Keywords: cholangiocarcinoma; chronic alcohol exposure; normal cholangiocyte; oncogenic feature; transcriptomic analysis cholangiocarcinoma; chronic alcohol exposure; normal cholangiocyte; oncogenic feature; transcriptomic analysis
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MDPI and ACS Style

Chujan, S.; Suriyo, T.; Satayavivad, J. Integrative In Silico and In Vitro Transcriptomics Analysis Revealed Gene Expression Changes and Oncogenic Features of Normal Cholangiocytes after Chronic Alcohol Exposure. Int. J. Mol. Sci. 2019, 20, 5987. https://doi.org/10.3390/ijms20235987

AMA Style

Chujan S, Suriyo T, Satayavivad J. Integrative In Silico and In Vitro Transcriptomics Analysis Revealed Gene Expression Changes and Oncogenic Features of Normal Cholangiocytes after Chronic Alcohol Exposure. International Journal of Molecular Sciences. 2019; 20(23):5987. https://doi.org/10.3390/ijms20235987

Chicago/Turabian Style

Chujan, Suthipong, Tawit Suriyo, and Jutamaad Satayavivad. 2019. "Integrative In Silico and In Vitro Transcriptomics Analysis Revealed Gene Expression Changes and Oncogenic Features of Normal Cholangiocytes after Chronic Alcohol Exposure" International Journal of Molecular Sciences 20, no. 23: 5987. https://doi.org/10.3390/ijms20235987

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