miR-1236 regulates epithelial-mesenchymal transition and metastatic activity through repressing sentrin-specific protease1(SENP1) and HDAC3
博士 === 國立陽明大學 === 生化暨分子生物研究所 === 105 === Intratumoral hypoxia induces epithelial–mesenchymal transition and promotes cancer metastasis. MicroRNAs (miRNAs) are endogenous, single-strand RNA molecules that regulate gene expression. MiRNAs control cell growth, proliferation, differentiation and cell de...
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ndltd-TW-105YM0051070042019-05-15T23:17:14Z http://ndltd.ncl.edu.tw/handle/tda32k miR-1236 regulates epithelial-mesenchymal transition and metastatic activity through repressing sentrin-specific protease1(SENP1) and HDAC3 miR-1236透過抑制組蛋白去乙醯酶3和Sentrin特定蛋白酶1表現而調控上皮細胞中胚轉化和癌細胞的轉移活性 Sung-Yuan Chen 陳松遠 博士 國立陽明大學 生化暨分子生物研究所 105 Intratumoral hypoxia induces epithelial–mesenchymal transition and promotes cancer metastasis. MicroRNAs (miRNAs) are endogenous, single-strand RNA molecules that regulate gene expression. MiRNAs control cell growth, proliferation, differentiation and cell death and may function as oncogenes or tumor suppressors. HDAC3 and SENP1 are two molecules involved in hypoxia-induced EMT and HIF-1α stability, respectively. In this proposal, we show that miR-1236 plays a critical role in hypoxia-induced EMT and metastasis. MiRNA prediction programs TargetScan and miRanda show that miR-1236 may target HDAC3 and SENP1. MiR-1236 represses the luciferase activity of reporter constructs containing 3’UTR of HDAC3 and SENP1 as well as the expression levels of HDAC3 and SENP1. MiR-1236 abolishes hypoxia-induced EMT and inhibits migration and invasion activity of tumor cells. Hypoxia represses miR-1236 expression. The promoter region of miR-1236 is identified as the NELFE promoter. Twist1, an EMT regulator activated by hypoxia/HIF-1α, is shown to repress the reporter construct driven by the NELFE promoter. The binding site of Twist1 in the NELFE promoter is identified and chromatin immunoprecipitation assays show the direct binding of Twist1 to this site. Overexpression or knockdown of Twist1 in stable cell lines shows the inverse correlation between Twist1 and miR-1236 expression. These results identify a miRNA that regulates hypoxia-induced EMT and metastasis through repressing HDAC3 and SENP1 expression and present a regulatory network that involves many key players in hypoxia-induced EMT. Kou-Juey Wu Tzu-Hao Cheng 吳國瑞 鄭子豪 2017 學位論文 ; thesis 80 en_US |
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博士 === 國立陽明大學 === 生化暨分子生物研究所 === 105 === Intratumoral hypoxia induces epithelial–mesenchymal transition and promotes cancer metastasis. MicroRNAs (miRNAs) are endogenous, single-strand RNA molecules that regulate gene expression. MiRNAs control cell growth, proliferation, differentiation and cell death and may function as oncogenes or tumor suppressors. HDAC3 and SENP1 are two molecules involved in hypoxia-induced EMT and HIF-1α stability, respectively. In this proposal, we show that miR-1236 plays a critical role in hypoxia-induced EMT and metastasis. MiRNA prediction programs TargetScan and miRanda show that miR-1236 may target HDAC3 and SENP1. MiR-1236 represses the luciferase activity of reporter constructs containing 3’UTR of HDAC3 and SENP1 as well as the expression levels of HDAC3 and SENP1. MiR-1236 abolishes hypoxia-induced EMT and inhibits migration and invasion activity of tumor cells. Hypoxia represses miR-1236 expression. The promoter region of miR-1236 is identified as the NELFE promoter. Twist1, an EMT regulator activated by hypoxia/HIF-1α, is shown to repress the reporter construct driven by the NELFE promoter. The binding site of Twist1 in the NELFE promoter is identified and chromatin immunoprecipitation assays show the direct binding of Twist1 to this site. Overexpression or knockdown of Twist1 in stable cell lines shows the inverse correlation between Twist1 and miR-1236 expression. These results identify a miRNA that regulates hypoxia-induced EMT and metastasis through repressing HDAC3 and SENP1 expression and present a regulatory network that involves many key players in hypoxia-induced EMT.
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author2 |
Kou-Juey Wu |
author_facet |
Kou-Juey Wu Sung-Yuan Chen 陳松遠 |
author |
Sung-Yuan Chen 陳松遠 |
spellingShingle |
Sung-Yuan Chen 陳松遠 miR-1236 regulates epithelial-mesenchymal transition and metastatic activity through repressing sentrin-specific protease1(SENP1) and HDAC3 |
author_sort |
Sung-Yuan Chen |
title |
miR-1236 regulates epithelial-mesenchymal transition and metastatic activity through repressing sentrin-specific protease1(SENP1) and HDAC3 |
title_short |
miR-1236 regulates epithelial-mesenchymal transition and metastatic activity through repressing sentrin-specific protease1(SENP1) and HDAC3 |
title_full |
miR-1236 regulates epithelial-mesenchymal transition and metastatic activity through repressing sentrin-specific protease1(SENP1) and HDAC3 |
title_fullStr |
miR-1236 regulates epithelial-mesenchymal transition and metastatic activity through repressing sentrin-specific protease1(SENP1) and HDAC3 |
title_full_unstemmed |
miR-1236 regulates epithelial-mesenchymal transition and metastatic activity through repressing sentrin-specific protease1(SENP1) and HDAC3 |
title_sort |
mir-1236 regulates epithelial-mesenchymal transition and metastatic activity through repressing sentrin-specific protease1(senp1) and hdac3 |
publishDate |
2017 |
url |
http://ndltd.ncl.edu.tw/handle/tda32k |
work_keys_str_mv |
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