Downregulation of Long Noncoding RNA Gas5 Affects Cell Cycle and Insulin Secretion in Mouse Pancreatic β Cells
Downregulation of Long Noncoding RNA Gas5 Affects Cell Cycle and Insulin Secretion in Mouse Pancreatic β Cells
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长非编码 RNA Gas5 的下调影响小鼠胰腺 β 细胞的细胞周期和胰岛素分泌
DOI：
10.1159/000484191
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发表时间：
2017-01-01
影响因子：
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通讯作者：
Tang, Wei
中科院分区：
文献类型：
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作者：
Jin, Feiyan;Wang, Ning;Tang, Wei
背景资料：有证据表明，长链非编码RNA（lncRNA）参与个体发育、细胞分化、细胞周期过程等重要生命过程，与包括糖尿病在内的人类重大疾病密切相关。最近的研究报道，lncRNA参与ss细胞的功能，并且在T2 DM患者的血清中lncRNA Gas 5水平降低。本研究的目的是阐明lncRNA Gas 5在小鼠ss细胞功能中的作用。方法：采用qRT-PCR方法检测2型糖尿病及正常小鼠组织中lncRNA Gas 5的表达。采用RNAi、qRT-PCR、Annexin V-FITC、western blot、GSIS和RIA等方法检测lncRNA Gas 5对胰岛素合成和分泌的影响。结果：db/db小鼠lncRNAGas 5水平显著降低。然而，lncRNA Gas 5在正常小鼠胰腺中的表达相对较高。IncRNA Gas 5表达的敲低导致细胞周期G1期阻滞，并损害Min 6细胞中胰岛素的合成和分泌。此外，在原代分离的胰岛中lncRNA Gas 5表达的敲低导致胰岛素基因和转录因子Pdx 1和MafA的表达降低。这些结果表明lncRNA Gas 5可能作为一种新的调节因子，通过影响胰岛素的合成和分泌来维持ss细胞的身份和功能。(C)2017作者由S.发布Karger AG，巴塞尔
Background: Evidence shows that long non-coding RNAs (lncRNAs) are involved in individual development, cell differentiation, cell cycle processes and other important life processes and are closely related to major human diseases, including diabetes. Recent studies have reported that lncRNAs are involved in ss cell functions and that lncRNA Gas5 levels decreased in T2DM patients' serum. The purpose of this study was to clarify the role of lncRNA Gas5 in mouse ss cell functions in vitro and in vivo. Methods: lncRNA Gas5 expression in T2DM and normal mouse tissues was analyzed using qRT-PCR. RNAi, qRT-PCR, Annexin V-FITC assays, western blot, GSIS and RIA were performed to detect the effects of lncRNA Gas5 on insulin synthesis and secretion in vitro and in vivo. Results: The lncRNA Gas5 level was significantly decreased in db/db mice. However, lncRNA Gas5 expression was relatively high in the pancreas of normal mice. Knockdown of lncRNA Gas5 expression led to cell cycle G1 arrest and impaired insulin synthesis and secretion in Min6 cells. Further, knockdown of lncRNA Gas5 expression in primary isolated islets resulted in decreased expression of insulin gene and transcription factors, Pdx1 and MafA. These results indicate that lncRNA Gas5 might perform as a new regulator, maintaining ss cell identity and function by affecting insulin synthesis and secretion. (C) 2017 The Author(s) Published by S. Karger AG, Basel