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MiR-126 Suppresses the Glucose-Stimulated Proliferation via IRS-2 in INS-1 β Cells
BACKGROUND: Increasing evidence suggests that miR-126 participates in the glucose homeostasis through its target molecules. Although bioinformatics analysis predicts that miR-126 can bind with the insulin receptor substrate-2(IRS-2) mRNA at the “seed sequence”, but there are still no definitely repo...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4769223/ https://www.ncbi.nlm.nih.gov/pubmed/26919700 http://dx.doi.org/10.1371/journal.pone.0149954 |
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author | Tao, Hong Wang, Meng-meng Zhang, Man Zhang, Shao-ping Wang, Chun-hui Yuan, Wen-jun Sun, Tao He, Lan-jie Hu, Qi-kuan |
author_facet | Tao, Hong Wang, Meng-meng Zhang, Man Zhang, Shao-ping Wang, Chun-hui Yuan, Wen-jun Sun, Tao He, Lan-jie Hu, Qi-kuan |
author_sort | Tao, Hong |
collection | PubMed |
description | BACKGROUND: Increasing evidence suggests that miR-126 participates in the glucose homeostasis through its target molecules. Although bioinformatics analysis predicts that miR-126 can bind with the insulin receptor substrate-2(IRS-2) mRNA at the “seed sequence”, but there are still no definitely reports to support it. In this study, we provided evidences that IRS-2 was one of the target genes of miR-126. And miR-126 has a proliferation inhibiting effects in INS-1 β cells, mainly through the suppression of IRS-2. METHODS: The 3’-UTR of IRS-2 regulated by miR-126 was analyzed by the luciferase assay and western blot. Furthermore, proliferation of INS-1 β cells stimulated by glucose was tested, and the association between IRS-2 and miR-126 were analyzed. RESULTS: We found that mutation of only three of the 6 “seed sequences” can eliminate the inhibition effect of miR-126. In INS-1 β cells, administration of miR-126 suppresses the proliferation, together with the unbalanced down-regulation of IRS-2 and IRS-1. Over-expression of IRS-2 can reverse the proliferation effect of miR-126, while not of IRS-1. These results suggested that miR-126 inhibited the β-cell proliferation via the inhibition of IRS-2 instead of IRS-1.Additionally, we also found that high glucose and insulin could stimulate the rapid production of endogenous miR-126 within 6 hours, together with the short term suppression of IRS-1 and IRS-2 expression, and intensify the unbalanced expression of IRS-1 and IRS-2. CONCLUSIONS: IRS-2 was one of the targets of miR-126. MiR-126 inhibited the β-cell proliferation through IRS-2 instead of IRS-1. MiR-126 may take part in the glucose homeostasis both through its target IRS-2 and IRS-1. The unbalance between IRS-1 and IRS-2 caused by miR-126 may play an important role in type 2 diabetes. |
format | Online Article Text |
id | pubmed-4769223 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-47692232016-03-09 MiR-126 Suppresses the Glucose-Stimulated Proliferation via IRS-2 in INS-1 β Cells Tao, Hong Wang, Meng-meng Zhang, Man Zhang, Shao-ping Wang, Chun-hui Yuan, Wen-jun Sun, Tao He, Lan-jie Hu, Qi-kuan PLoS One Research Article BACKGROUND: Increasing evidence suggests that miR-126 participates in the glucose homeostasis through its target molecules. Although bioinformatics analysis predicts that miR-126 can bind with the insulin receptor substrate-2(IRS-2) mRNA at the “seed sequence”, but there are still no definitely reports to support it. In this study, we provided evidences that IRS-2 was one of the target genes of miR-126. And miR-126 has a proliferation inhibiting effects in INS-1 β cells, mainly through the suppression of IRS-2. METHODS: The 3’-UTR of IRS-2 regulated by miR-126 was analyzed by the luciferase assay and western blot. Furthermore, proliferation of INS-1 β cells stimulated by glucose was tested, and the association between IRS-2 and miR-126 were analyzed. RESULTS: We found that mutation of only three of the 6 “seed sequences” can eliminate the inhibition effect of miR-126. In INS-1 β cells, administration of miR-126 suppresses the proliferation, together with the unbalanced down-regulation of IRS-2 and IRS-1. Over-expression of IRS-2 can reverse the proliferation effect of miR-126, while not of IRS-1. These results suggested that miR-126 inhibited the β-cell proliferation via the inhibition of IRS-2 instead of IRS-1.Additionally, we also found that high glucose and insulin could stimulate the rapid production of endogenous miR-126 within 6 hours, together with the short term suppression of IRS-1 and IRS-2 expression, and intensify the unbalanced expression of IRS-1 and IRS-2. CONCLUSIONS: IRS-2 was one of the targets of miR-126. MiR-126 inhibited the β-cell proliferation through IRS-2 instead of IRS-1. MiR-126 may take part in the glucose homeostasis both through its target IRS-2 and IRS-1. The unbalance between IRS-1 and IRS-2 caused by miR-126 may play an important role in type 2 diabetes. Public Library of Science 2016-02-26 /pmc/articles/PMC4769223/ /pubmed/26919700 http://dx.doi.org/10.1371/journal.pone.0149954 Text en © 2016 Tao et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Tao, Hong Wang, Meng-meng Zhang, Man Zhang, Shao-ping Wang, Chun-hui Yuan, Wen-jun Sun, Tao He, Lan-jie Hu, Qi-kuan MiR-126 Suppresses the Glucose-Stimulated Proliferation via IRS-2 in INS-1 β Cells |
title | MiR-126 Suppresses the Glucose-Stimulated Proliferation via IRS-2 in INS-1 β Cells |
title_full | MiR-126 Suppresses the Glucose-Stimulated Proliferation via IRS-2 in INS-1 β Cells |
title_fullStr | MiR-126 Suppresses the Glucose-Stimulated Proliferation via IRS-2 in INS-1 β Cells |
title_full_unstemmed | MiR-126 Suppresses the Glucose-Stimulated Proliferation via IRS-2 in INS-1 β Cells |
title_short | MiR-126 Suppresses the Glucose-Stimulated Proliferation via IRS-2 in INS-1 β Cells |
title_sort | mir-126 suppresses the glucose-stimulated proliferation via irs-2 in ins-1 β cells |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4769223/ https://www.ncbi.nlm.nih.gov/pubmed/26919700 http://dx.doi.org/10.1371/journal.pone.0149954 |
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