Cited by 984MicroRNA in disease regulationCholangiocarcinoma and Gallbladder Cancer StudiesCancer-related molecular mechanisms research

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Involvement of Human Micro-RNA in Growth and Response to Chemotherapy in Human Cholangiocarcinoma Cell Lines

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Meng, Fanyin, Henson, Roger, Lang, Molly, Wehbe, Hania, Maheshwari, Shail, Mendell, Joshua T., Jiang, Jinmai, Schmittgen, Thomas D., Patel, Tushar·2006·Gastroenterology

DOI 10.1053/j.gastro.2006.02.057

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Abstract

Background & aims Micro-RNA (miRNA) are endogenous regulatory RNA molecules that modulate gene expression. Alterations in miRNA expression can contribute to tumor growth by modulating the functional expression of critical genes involved in tumor cell proliferation or survival. Our aims were to identify specific miRNA involved in the regulation of cholangiocarcinoma growth and response to chemotherapy. Methods miRNA expression in malignant and nonmalignant human cholangiocytes was assessed using a microarray. Expression of selected miRNA and their precursors was evaluated by Northern blots and real-time polymerase chain reaction, respectively. The effect of selected miRNA on cell growth and response to chemotherapy was assessed using miRNA-specific antisense oligonucleotides to decrease miRNA expression or with precursor miRNA to increase cellular expression. Results miRNA expression was markedly different in malignant cholangiocytes, with decreased expression of many miRNA compared with nonmalignant cells. A cluster of miRNA, including miR-320, miR-200b, miR-21, miR-23a, miR-141, miR-27a, and miR-34a, were expressed in all cell lines. MiR-21, miR-141, and miR-200b were highly over-expressed in malignant cholangiocytes. Inhibition of miR-21 and miR-200b increased sensitivity to gemcitabine, whereas inhibition of miR-141 decreased cell growth. Treatment of tumor cell xenografts with systemic gemcitabine altered the expression of a significant number of miRNA. miR-21 modulates gemcitabine-induced apoptosis by phosphatase and tensin homolog deleted on chromosome 10 (PTEN)-dependent activation of PI 3-kinase signaling. Potential target genes that were modulated by selected miRNA were identified. Conclusions Alterations in miRNA expression contribute to tumor growth and response to chemotherapy. Aberrantly expressed miRNA or their targets will provide mechanistic insight and therapeutic targets for cholangiocarcinoma.

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Authors: Meng, F., Henson, R., Lang, M., Wehbe, H., Maheshwari, S., Mendell, J. T., Jiang, J., Schmittgen, T. D., & Patel, T.
Affiliations: Texas A&M University System (US)
Johns Hopkins University (US)
The Ohio State University (US)
Corresponding author: Patel, Tushar
ORCID: Meng, Fanyin
Mendell, Joshua T.
Jiang, Jinmai
Schmittgen, Thomas D.
Patel, Tushar
Venue: Gastroenterology
Publisher: Elsevier BV
Published: 2006-06
Volume: 130
Issue: 7
Pages: 2113-2129
ISSN: 0016-5085 (ISSN-L)
DOI: 10.1053/j.gastro.2006.02.057
OpenAlex: W1990645475
Cited by: 984
References: 44
Citations by year: 2026: 9 · 2025: 19 · 2024: 13 · 2023: 24 · 2022: 26 · 2021: 27 · 2020: 22 · 2019: 28 · 2018: 27 · 2017: 49 · 2016: 60 · 2015: 64 · 2014: 86 · 2013: 76 · 2012: 65
FWCI: 27.56
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Gastroenterology (publishedVersion)
PubMed (publishedVersion)
OakTrust (Texas A&M University Libraries) (submittedVersion)
Funders: National Institutes of Health
National Institute of Diabetes and Digestive and Kidney Diseases (DK-069370, R01DK069370)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
Health Sciences › Medicine › Surgery › Cholangiocarcinoma and Gallbladder Cancer Studies
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
Keywords: microRNA, cholangiocarcinoma, miR-21, miR-200b, miR-141, gemcitabine, chemotherapy response, tumor cell proliferation, PTEN, PI3K signaling, apoptosis, miRNA expression profiling, cholangiocytes, xenografts, therapeutic target
MeSH terms: Gemcitabine, Animals, Deoxycytidine, Humans, Male, Mice, Nude, Probability, Sampling Studies, Sensitivity and Specificity, Transfection, Transplantation, Heterologous, Blotting, Northern, Blotting, Western, Gene Expression Regulation, Neoplastic, Apoptosis, Cholangiocarcinoma, Reverse Transcriptase Polymerase Chain Reaction, Oligonucleotide Array Sequence Analysis, Gene Expression Profiling, MicroRNAs, Cell Line, Tumor, Cell Proliferation, Mice

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Involvement of Human Micro-RNA in Growth and Response to Chemotherapy in Human Cholangiocarcinoma Cell Lines

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