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Notch1 pathway-mediated microRNA-151-5p promotes gastric cancer progression
Gastric carcinoma is the third leading cause of lethal cancer worldwide. Previous studies showed that Notch1 receptor intracellular domain (N1IC), the activated form of Notch1 receptor, promotes gastric cancer progression. It has been demonstrated that a significant cross-talk interplays between Not...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5122370/ https://www.ncbi.nlm.nih.gov/pubmed/27191259 http://dx.doi.org/10.18632/oncotarget.9342 |
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author | Hsu, Kai-Wen Fang, Wen-Liang Huang, Kuo-Hung Huang, Tzu-Ting Lee, Hsin-Chen Hsieh, Rong-Hong Chi, Chin-Wen Yeh, Tien-Shun |
author_facet | Hsu, Kai-Wen Fang, Wen-Liang Huang, Kuo-Hung Huang, Tzu-Ting Lee, Hsin-Chen Hsieh, Rong-Hong Chi, Chin-Wen Yeh, Tien-Shun |
author_sort | Hsu, Kai-Wen |
collection | PubMed |
description | Gastric carcinoma is the third leading cause of lethal cancer worldwide. Previous studies showed that Notch1 receptor intracellular domain (N1IC), the activated form of Notch1 receptor, promotes gastric cancer progression. It has been demonstrated that a significant cross-talk interplays between Notch pathways and microRNAs (miRNAs) in controlling tumorigenesis. This study identified an intronic microRNA-151 (miR-151), which consists of two mature miRNAs, miR-151-3p and miR-151-5p, as a Notch1 receptor-induced miRNA in gastric cancer cells. Activation of Notch1 pathway enhanced expressions of miR-151 and its host gene, focal adhesion kinase (FAK), in gastric cancer cells. The levels of miR-151 in gastric cancer samples were higher than those of adjacent non-tumor samples. Activated Notch1 pathway induced CBF1-dependent FAK promoter activity. The ectopic expression of miR-151 promoted growth and progression of SC-M1 gastric cancer cells including cell viability and colony formation, migration, and invasion abilities. Activated Notch1 pathway could augment progression of gastric cancer cells through miR-151-5p and FAK. The mRNA levels of pluripotency genes, Nanog and SOX-2, tumorsphere formation ability, tumor growth, and lung metastasis of SC-M1 cells were elevated by activated Notch1 pathway through miR-151-5p. Furthermore, miR-151-5p could target 3′-untranslated region (3′-UTR) of p53 mRNA and down-regulate p53 level in SC-M1 cells. Mechanistically, Notch1/miR-151-5p axis contributed to progression of SC-M1 cells through down-regulation of p53 which in turn repressed FAK promoter activity. Taken together, these results suggest that Notch1 pathway and miR-151-5p interplay with p53 in a reciprocal regulation loop in controlling gastric carcinogenesis. |
format | Online Article Text |
id | pubmed-5122370 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-51223702016-12-05 Notch1 pathway-mediated microRNA-151-5p promotes gastric cancer progression Hsu, Kai-Wen Fang, Wen-Liang Huang, Kuo-Hung Huang, Tzu-Ting Lee, Hsin-Chen Hsieh, Rong-Hong Chi, Chin-Wen Yeh, Tien-Shun Oncotarget Research Paper Gastric carcinoma is the third leading cause of lethal cancer worldwide. Previous studies showed that Notch1 receptor intracellular domain (N1IC), the activated form of Notch1 receptor, promotes gastric cancer progression. It has been demonstrated that a significant cross-talk interplays between Notch pathways and microRNAs (miRNAs) in controlling tumorigenesis. This study identified an intronic microRNA-151 (miR-151), which consists of two mature miRNAs, miR-151-3p and miR-151-5p, as a Notch1 receptor-induced miRNA in gastric cancer cells. Activation of Notch1 pathway enhanced expressions of miR-151 and its host gene, focal adhesion kinase (FAK), in gastric cancer cells. The levels of miR-151 in gastric cancer samples were higher than those of adjacent non-tumor samples. Activated Notch1 pathway induced CBF1-dependent FAK promoter activity. The ectopic expression of miR-151 promoted growth and progression of SC-M1 gastric cancer cells including cell viability and colony formation, migration, and invasion abilities. Activated Notch1 pathway could augment progression of gastric cancer cells through miR-151-5p and FAK. The mRNA levels of pluripotency genes, Nanog and SOX-2, tumorsphere formation ability, tumor growth, and lung metastasis of SC-M1 cells were elevated by activated Notch1 pathway through miR-151-5p. Furthermore, miR-151-5p could target 3′-untranslated region (3′-UTR) of p53 mRNA and down-regulate p53 level in SC-M1 cells. Mechanistically, Notch1/miR-151-5p axis contributed to progression of SC-M1 cells through down-regulation of p53 which in turn repressed FAK promoter activity. Taken together, these results suggest that Notch1 pathway and miR-151-5p interplay with p53 in a reciprocal regulation loop in controlling gastric carcinogenesis. Impact Journals LLC 2016-05-13 /pmc/articles/PMC5122370/ /pubmed/27191259 http://dx.doi.org/10.18632/oncotarget.9342 Text en Copyright: © 2016 Hsu et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Hsu, Kai-Wen Fang, Wen-Liang Huang, Kuo-Hung Huang, Tzu-Ting Lee, Hsin-Chen Hsieh, Rong-Hong Chi, Chin-Wen Yeh, Tien-Shun Notch1 pathway-mediated microRNA-151-5p promotes gastric cancer progression |
title | Notch1 pathway-mediated microRNA-151-5p promotes gastric cancer progression |
title_full | Notch1 pathway-mediated microRNA-151-5p promotes gastric cancer progression |
title_fullStr | Notch1 pathway-mediated microRNA-151-5p promotes gastric cancer progression |
title_full_unstemmed | Notch1 pathway-mediated microRNA-151-5p promotes gastric cancer progression |
title_short | Notch1 pathway-mediated microRNA-151-5p promotes gastric cancer progression |
title_sort | notch1 pathway-mediated microrna-151-5p promotes gastric cancer progression |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5122370/ https://www.ncbi.nlm.nih.gov/pubmed/27191259 http://dx.doi.org/10.18632/oncotarget.9342 |
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