miR-101 Inhibits Cholangiocarcinoma Angiogenesis through Targeting Vascular Endothelial Growth Factor (VEGF)

HIF1A
DOI: 10.1016/j.ajpath.2013.01.045 Publication Date: 2013-04-20T01:17:59Z
ABSTRACT
Recent evidence has suggested an important role of miRNAs in liver biology and diseases, although the implication cholangiocarcinoma remains to be defined further. This study was designed examine biological function molecular mechanism miR-101 cholangiocarcinogenesis tumor progression. In situ hybridization quantitative RT-PCR were performed determine expression human tissues cell lines. Compared with noncancerous biliary epithelial cells, is decreased 43.5% specimens all three lines used this study. Forced overexpression significantly inhibited growth severe combined immunodeficiency mice. miR-101-overexpressed xenograft showed capillary densities levels vascular endothelial factor (VEGF) cyclooxygenase-2 (COX-2). The VEGF COX-2 mRNAs identified as bona fide targets cells by both computational analysis experimental assays. inhibits angiogenesis direct targeting mRNA 3'untranslated region repression gene transcription through inhibition COX-2. established a novel tumor-suppressor it suggests possibility related signaling pathways for future therapy.
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