Down‐regulation of miR‐214 contributes to intrahepatic cholangiocarcinoma metastasis by targeting Twist

miRNAs play an important role in many human diseases, including cancer metastasis. However, the mechanisms by which miRNAs regulate intrahepatic cholangiocarcinoma metastasis remain poorly understood. In the present study, we assayed the expression level of miR‐214 in intrahepatic cholangiocarcinoma...

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Veröffentlicht in:The FEBS journal 2012-07, Vol.279 (13), p.2393-2398
Hauptverfasser: Li, Bin, Han, Qingqi, Zhu, Yan, Yu, Yong, Wang, Jinghan, Jiang, Xiaoqing
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Han, Qingqi
Zhu, Yan
Yu, Yong
Wang, Jinghan
Jiang, Xiaoqing
description miRNAs play an important role in many human diseases, including cancer metastasis. However, the mechanisms by which miRNAs regulate intrahepatic cholangiocarcinoma metastasis remain poorly understood. In the present study, we assayed the expression level of miR‐214 in intrahepatic cholangiocarcinoma tissues by real‐time PCR, and defined the target gene and biological function by luciferase reporter assay and Western blot analysis. We found that the miR‐214 levels were remarkably decreased in metastatic intrahepatic cholangiocarcinoma tissues compared to non‐metastatic tissues. Inhibition of miR‐214 levels by its inhibitor promoted metastasis of human intrahepatic cholangiocarcinoma cell. We further demonstrated that down‐regulation of miR‐214 increased the transcript levels of the epithelial–mesenchymal transition‐associated gene Twist, and then decreased E‐cadherin levels. We confirmed that down‐regulation of miR‐214 promoted the epithelial–mesenchymal transition by directly targeting the Twist gene. These results suggest an important role for miR‐214 in regulating metastasis of intrahepatic cholangiocarcinoma, and potential application of miR‐214 in intrahepatic cholangiocarcinoma therapy. miR‐214 levels were remarkably decreased in metastatic intrahepatic cholangiocarcinoma tissues compared to non‐metastatic tissues. Inhibition of miR‐214 levels by its inhibitor promoted metastasis of human intrahepatic cholangiocarcinoma cells. Downregulated miR‐214 increased the levels of the EMT‐associated gene Twist, and decreased E‐cadherin levels. We confirmed that downregulated miR‐214 promoted EMT by directly targeting the Twist gene.
doi_str_mv 10.1111/j.1742-4658.2012.08618.x
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These results suggest an important role for miR‐214 in regulating metastasis of intrahepatic cholangiocarcinoma, and potential application of miR‐214 in intrahepatic cholangiocarcinoma therapy. miR‐214 levels were remarkably decreased in metastatic intrahepatic cholangiocarcinoma tissues compared to non‐metastatic tissues. Inhibition of miR‐214 levels by its inhibitor promoted metastasis of human intrahepatic cholangiocarcinoma cells. Downregulated miR‐214 increased the levels of the EMT‐associated gene Twist, and decreased E‐cadherin levels. 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However, the mechanisms by which miRNAs regulate intrahepatic cholangiocarcinoma metastasis remain poorly understood. In the present study, we assayed the expression level of miR‐214 in intrahepatic cholangiocarcinoma tissues by real‐time PCR, and defined the target gene and biological function by luciferase reporter assay and Western blot analysis. We found that the miR‐214 levels were remarkably decreased in metastatic intrahepatic cholangiocarcinoma tissues compared to non‐metastatic tissues. Inhibition of miR‐214 levels by its inhibitor promoted metastasis of human intrahepatic cholangiocarcinoma cell. We further demonstrated that down‐regulation of miR‐214 increased the transcript levels of the epithelial–mesenchymal transition‐associated gene Twist, and then decreased E‐cadherin levels. We confirmed that down‐regulation of miR‐214 promoted the epithelial–mesenchymal transition by directly targeting the Twist gene. These results suggest an important role for miR‐214 in regulating metastasis of intrahepatic cholangiocarcinoma, and potential application of miR‐214 in intrahepatic cholangiocarcinoma therapy. miR‐214 levels were remarkably decreased in metastatic intrahepatic cholangiocarcinoma tissues compared to non‐metastatic tissues. Inhibition of miR‐214 levels by its inhibitor promoted metastasis of human intrahepatic cholangiocarcinoma cells. Downregulated miR‐214 increased the levels of the EMT‐associated gene Twist, and decreased E‐cadherin levels. 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However, the mechanisms by which miRNAs regulate intrahepatic cholangiocarcinoma metastasis remain poorly understood. In the present study, we assayed the expression level of miR‐214 in intrahepatic cholangiocarcinoma tissues by real‐time PCR, and defined the target gene and biological function by luciferase reporter assay and Western blot analysis. We found that the miR‐214 levels were remarkably decreased in metastatic intrahepatic cholangiocarcinoma tissues compared to non‐metastatic tissues. Inhibition of miR‐214 levels by its inhibitor promoted metastasis of human intrahepatic cholangiocarcinoma cell. We further demonstrated that down‐regulation of miR‐214 increased the transcript levels of the epithelial–mesenchymal transition‐associated gene Twist, and then decreased E‐cadherin levels. We confirmed that down‐regulation of miR‐214 promoted the epithelial–mesenchymal transition by directly targeting the Twist gene. These results suggest an important role for miR‐214 in regulating metastasis of intrahepatic cholangiocarcinoma, and potential application of miR‐214 in intrahepatic cholangiocarcinoma therapy. miR‐214 levels were remarkably decreased in metastatic intrahepatic cholangiocarcinoma tissues compared to non‐metastatic tissues. Inhibition of miR‐214 levels by its inhibitor promoted metastasis of human intrahepatic cholangiocarcinoma cells. Downregulated miR‐214 increased the levels of the EMT‐associated gene Twist, and decreased E‐cadherin levels. We confirmed that downregulated miR‐214 promoted EMT by directly targeting the Twist gene.</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>22540680</pmid><doi>10.1111/j.1742-4658.2012.08618.x</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record>
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subjects Bile Duct Neoplasms
Bile Ducts, Intrahepatic
Biochemistry
Blotting, Western
Cancer
Cell Line, Tumor
Cell Movement
Cholangiocarcinoma - genetics
Cholangiocarcinoma - metabolism
Cholangiocarcinoma - secondary
Down-Regulation
Epithelial-Mesenchymal Transition
E‐cadherin
Gene Expression Regulation, Neoplastic - genetics
Humans
intrahepatic cholangiocarcinoma
Liver Neoplasms - genetics
Liver Neoplasms - metabolism
Liver Neoplasms - secondary
Luciferases - metabolism
Metastasis
MicroRNAs - genetics
MicroRNAs - metabolism
miR214
Nuclear Proteins - genetics
Nuclear Proteins - metabolism
Real-Time Polymerase Chain Reaction
Reverse Transcriptase Polymerase Chain Reaction
Ribonucleic acid
RNA
RNA, Messenger - genetics
Twist
Twist-Related Protein 1 - genetics
Twist-Related Protein 1 - metabolism
title Down‐regulation of miR‐214 contributes to intrahepatic cholangiocarcinoma metastasis by targeting Twist
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