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MiR-467a is Upregulated in Radiation-Induced Mouse Thymic Lymphomas and Regulates Apoptosis by Targeting Fas and Bax
It has been reported dysregulation of certain microRNAs (miRNAs / miRs) is involved in tumorigenesis. However, the miRNAs associated with radiocarcinogenesis remain undefined. In this study, we validated the upregulation of miR-467a in radiation-induced mouse thymic lymphoma tissues. Then, we invest...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Ivyspring International Publisher
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4278260/ https://www.ncbi.nlm.nih.gov/pubmed/25552935 http://dx.doi.org/10.7150/ijbs.10276 |
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author | Gao, Fu Chen, Song Sun, Mingjuan Mitchel, Ronald E.J. Li, Bailong Chu, Zhiyong Cai, Jianming Liu, Cong |
author_facet | Gao, Fu Chen, Song Sun, Mingjuan Mitchel, Ronald E.J. Li, Bailong Chu, Zhiyong Cai, Jianming Liu, Cong |
author_sort | Gao, Fu |
collection | PubMed |
description | It has been reported dysregulation of certain microRNAs (miRNAs / miRs) is involved in tumorigenesis. However, the miRNAs associated with radiocarcinogenesis remain undefined. In this study, we validated the upregulation of miR-467a in radiation-induced mouse thymic lymphoma tissues. Then, we investigated whether miR-467a functions as an oncogenic miRNA in thymic lymphoma cells. For this purpose, we assessed the biological effect of miR-467a on thymic lymphoma cells. Using miRNA microarray, we found four miRNAs (miR-467a, miR-762, miR-455 and miR-714) were among the most upregulated (>4-fold) miRNAs in tumor tissues. Bioinformatics prediction suggests miR-467a may potentially regulate apoptosis pathway via targeting Fas and Bax. Consistently, in miR-467a-transfected cells, both proliferation and colony formation ability were significantly increased with decrease of apoptosis rate, while, in miR-467a-knockdown cells, proliferation was suppressed with increase of apoptosis rate, indicating that miR-467a may be involved in the regulation of apoptosis. Furthermore, miR-467a-knockdown resulted in smaller tumors and better prognosis in an in vivo tumor-transplanted model. To explain the mechanism of apoptosis suppression by miR-467a, we explore the expression of candidate target genes (Fas and Bax) in miR-467a-transfected relative to negative control transfected cells using flow cytometry and immunoblotting. Fas and Bax were commonly downregulated in miR-467a-transfected EL4 and NIH3T3 cells, and all of the genes harbored miR-467a target sequences in the 3'UTR of their mRNA. Fas and Bax were actually downregulated in radiation-induced thymic lymphoma tissues, and therefore both were identified as possible targets of miR-467a in thymic lymphoma. To ascertain whether downregulation of Fas and / or Bax is involved in apoptosis suppression by miR-467a, we transfected vectors expressing Fas and Bax into miR-467a-upregulated EL4 cells. Then we found that both Fas- and Bax-overexpression decreased cell viability with increase of apoptosis rate, indicating that downregulation of Fas and Bax may be at least partly responsible for apoptosis suppression by miR-467a. These data suggest that miR-467a may have oncogenic functions in radiation-induced thymic lymphoma cells and that its increased expression may confer a growth advantage on tumor cells via aberrant expression of Fas and Bax. |
format | Online Article Text |
id | pubmed-4278260 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Ivyspring International Publisher |
record_format | MEDLINE/PubMed |
spelling | pubmed-42782602015-01-01 MiR-467a is Upregulated in Radiation-Induced Mouse Thymic Lymphomas and Regulates Apoptosis by Targeting Fas and Bax Gao, Fu Chen, Song Sun, Mingjuan Mitchel, Ronald E.J. Li, Bailong Chu, Zhiyong Cai, Jianming Liu, Cong Int J Biol Sci Research Paper It has been reported dysregulation of certain microRNAs (miRNAs / miRs) is involved in tumorigenesis. However, the miRNAs associated with radiocarcinogenesis remain undefined. In this study, we validated the upregulation of miR-467a in radiation-induced mouse thymic lymphoma tissues. Then, we investigated whether miR-467a functions as an oncogenic miRNA in thymic lymphoma cells. For this purpose, we assessed the biological effect of miR-467a on thymic lymphoma cells. Using miRNA microarray, we found four miRNAs (miR-467a, miR-762, miR-455 and miR-714) were among the most upregulated (>4-fold) miRNAs in tumor tissues. Bioinformatics prediction suggests miR-467a may potentially regulate apoptosis pathway via targeting Fas and Bax. Consistently, in miR-467a-transfected cells, both proliferation and colony formation ability were significantly increased with decrease of apoptosis rate, while, in miR-467a-knockdown cells, proliferation was suppressed with increase of apoptosis rate, indicating that miR-467a may be involved in the regulation of apoptosis. Furthermore, miR-467a-knockdown resulted in smaller tumors and better prognosis in an in vivo tumor-transplanted model. To explain the mechanism of apoptosis suppression by miR-467a, we explore the expression of candidate target genes (Fas and Bax) in miR-467a-transfected relative to negative control transfected cells using flow cytometry and immunoblotting. Fas and Bax were commonly downregulated in miR-467a-transfected EL4 and NIH3T3 cells, and all of the genes harbored miR-467a target sequences in the 3'UTR of their mRNA. Fas and Bax were actually downregulated in radiation-induced thymic lymphoma tissues, and therefore both were identified as possible targets of miR-467a in thymic lymphoma. To ascertain whether downregulation of Fas and / or Bax is involved in apoptosis suppression by miR-467a, we transfected vectors expressing Fas and Bax into miR-467a-upregulated EL4 cells. Then we found that both Fas- and Bax-overexpression decreased cell viability with increase of apoptosis rate, indicating that downregulation of Fas and Bax may be at least partly responsible for apoptosis suppression by miR-467a. These data suggest that miR-467a may have oncogenic functions in radiation-induced thymic lymphoma cells and that its increased expression may confer a growth advantage on tumor cells via aberrant expression of Fas and Bax. Ivyspring International Publisher 2015-01-01 /pmc/articles/PMC4278260/ /pubmed/25552935 http://dx.doi.org/10.7150/ijbs.10276 Text en © Ivyspring International Publisher. This is an open-access article distributed under the terms of the Creative Commons License (http://creativecommons.org/licenses/by-nc-nd/3.0/). Reproduction is permitted for personal, noncommercial use, provided that the article is in whole, unmodified, and properly cited. |
spellingShingle | Research Paper Gao, Fu Chen, Song Sun, Mingjuan Mitchel, Ronald E.J. Li, Bailong Chu, Zhiyong Cai, Jianming Liu, Cong MiR-467a is Upregulated in Radiation-Induced Mouse Thymic Lymphomas and Regulates Apoptosis by Targeting Fas and Bax |
title | MiR-467a is Upregulated in Radiation-Induced Mouse Thymic Lymphomas and Regulates Apoptosis by Targeting Fas and Bax |
title_full | MiR-467a is Upregulated in Radiation-Induced Mouse Thymic Lymphomas and Regulates Apoptosis by Targeting Fas and Bax |
title_fullStr | MiR-467a is Upregulated in Radiation-Induced Mouse Thymic Lymphomas and Regulates Apoptosis by Targeting Fas and Bax |
title_full_unstemmed | MiR-467a is Upregulated in Radiation-Induced Mouse Thymic Lymphomas and Regulates Apoptosis by Targeting Fas and Bax |
title_short | MiR-467a is Upregulated in Radiation-Induced Mouse Thymic Lymphomas and Regulates Apoptosis by Targeting Fas and Bax |
title_sort | mir-467a is upregulated in radiation-induced mouse thymic lymphomas and regulates apoptosis by targeting fas and bax |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4278260/ https://www.ncbi.nlm.nih.gov/pubmed/25552935 http://dx.doi.org/10.7150/ijbs.10276 |
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