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 defini...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2016-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4769223?pdf=render |
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| author | Hong Tao Meng-meng Wang Man Zhang Shao-ping Zhang Chun-hui Wang Wen-jun Yuan Tao Sun Lan-jie He Qi-kuan Hu |
| author_facet | Hong Tao Meng-meng Wang Man Zhang Shao-ping Zhang Chun-hui Wang Wen-jun Yuan Tao Sun Lan-jie He Qi-kuan Hu |
| author_sort | Hong Tao |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-12T02:42:26Z |
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| id | doaj.art-ba7115f834e645d4a7396ac3443e0f67 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-12T02:42:26Z |
| publishDate | 2016-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-ba7115f834e645d4a7396ac3443e0f672022-12-22T00:41:08ZengPublic Library of Science (PLoS)PLoS ONE1932-62032016-01-01112e014995410.1371/journal.pone.0149954MiR-126 Suppresses the Glucose-Stimulated Proliferation via IRS-2 in INS-1 β Cells.Hong TaoMeng-meng WangMan ZhangShao-ping ZhangChun-hui WangWen-jun YuanTao SunLan-jie HeQi-kuan HuBACKGROUND: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.http://europepmc.org/articles/PMC4769223?pdf=render |
| spellingShingle | Hong Tao Meng-meng Wang Man Zhang Shao-ping Zhang Chun-hui Wang Wen-jun Yuan Tao Sun Lan-jie He Qi-kuan Hu MiR-126 Suppresses the Glucose-Stimulated Proliferation via IRS-2 in INS-1 β Cells. PLoS ONE |
| 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 |
| url | http://europepmc.org/articles/PMC4769223?pdf=render |
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