MicroRNA-185 targets SOCS3 to inhibit beta-cell dysfunction in diabetes.
MicroRNA-185 targets SOCS3 to inhibit beta-cell dysfunction in diabetes.
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DOI：
10.1371/journal.pone.0116067
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Lv H
中科院分区：
文献类型：
--
作者：
Bao L;Fu X;Si M;Wang Y;Ma R;Ren X;Lv H
糖尿病是最常见和最复杂的代谢紊乱，是当今最重要的健康威胁之一。MicroRNA（miRNAs）是一类小的非编码RNA，在葡萄糖稳态等多种生理过程中发挥重要作用。在这项研究中，我们研究了miR-185在糖尿病中的作用。miR-185在糖尿病患者和小鼠中显著下调，且低水平与血糖浓度相关。过表达miR-185可促进胰岛β细胞胰岛素分泌，促进细胞增殖，保护细胞免于凋亡。使用计算机模拟预测、荧光素酶报告基因测定和蛋白质印迹测定的进一步实验证明，miR-185通过结合其3 '-UTR直接靶向SOCS 3。与miR-185的保护作用相反，SOCS 3显著抑制β细胞的功能并灭活Stat 3通路。当用miR-185模拟物与SOCS 3过表达质粒组合处理细胞时，SOCS 3的抑制作用被逆转。而与单独的miR-185模拟物或SOCS 3 siRNA处理相比，miR-185模拟物和SOCS 3 siRNA的组合处理诱导协同促进作用。此外，我们观察到糖尿病患者中miR-185水平与SOCS 3表达呈负相关。总之，这项研究揭示了miR-185和SOCS 3在糖尿病发病机制中的功能和机制联系。MiR-185在糖尿病胰岛素分泌和β细胞生长的调节中起重要作用。miR-185表达的恢复可能为糖尿病提供一种潜在的有前景和有效的治疗方法。
Diabetes is the most common and complex metabolic disorder, and one of the most important health threats now. MicroRNAs (miRNAs) are a group of small non-coding RNAs that have been suggested to play a vital role in a variety of physiological processes, including glucose homeostasis. In this study, we investigated the role of miR-185 in diabetes. MiR-185 was significantly downregulated in diabetic patients and mice, and the low level was correlated to blood glucose concentration. Overexpression of miR-185 enhanced insulin secretion of pancreatic β-cells, promoted cell proliferation and protected cells from apoptosis. Further experiments using in silico prediction, luciferase reporter assay and western blot assay demonstrated that miR-185 directly targeted SOCS3 by binding to its 3’-UTR. On the contrary to miR-185’s protective effects, SOCS3 significantly suppressed functions of β-cell and inactivated Stat3 pathway. When treating cells with miR-185 mimics in combination with SOCS3 overexpression plasmid, the inhibitory effects of SOCS3 were reversed. While combined treatment of miR-185 mimics and SOCS3 siRNA induced synergistically promotive effects compared to either miR-185 mimics or SOCS3 siRNA treatment alone. Moreover, we observed that miR-185 level was inversely correlated with SOCS3 expression in diabetes patients. In conclusion, this study revealed a functional and mechanistic link between miR-185 and SOCS3 in the pathogenesis of diabetes. MiR-185 plays an important role in the regulation of insulin secretion and β-cell growth in diabetes. Restoration of miR-185 expression may serve a potentially promising and efficient therapeutic approach for diabetes.
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DOI：
10.1016/s0140-6736(14)60613-9
发表时间：
2014-06-07
期刊：
Lancet (London, England)
影响因子：
--
作者：
Ley SH;Hamdy O;Mohan V;Hu FB
通讯作者：
Hu FB
影响因子：
7.4
作者：
Kato, Mitsuo;Castro, Nancy E.;Natarajan, Rama
通讯作者：
Natarajan, Rama
影响因子：
3.7
作者：
Lovis, Pascal;Gattesco, Sonia;Regazzi, Romano
通讯作者：
Regazzi, Romano
影响因子：
8
作者：
Imam, J. S.;Buddavarapu, K.;Rao, M. K.
通讯作者：
Rao, M. K.
影响因子：
4.8
作者：
Plaisance, Valerie;Abderrahmani, Amar;Regazzi, Romano
通讯作者：
Regazzi, Romano