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长链非编码 RNA uc.322 的表达特征及其对胰岛功能的影响。

Expression characteristics of long noncoding RNA uc.322 and its effects on pancreatic islet function.

机构信息

Division of Geriatrics, Drum Tower Clinic Medical College of Nanjing Medical University, Nanjing, China.

Division of Endocrinology, The Affiliated Hospital of Nantong University, Nantong, China.

出版信息

J Cell Biochem. 2018 Nov;119(11):9239-9248. doi: 10.1002/jcb.27191. Epub 2018 Jun 28.

Abstract

Increasing evidence indicates that long noncoding RNAs (lncRNAs) perform special biological functions by regulating gene expression through multiple pathways and molecular mechanisms. The aim of this study was to explore the expression characteristics of lncRNA uc.322 in pancreatic islet cells and its effects on the secretion function of islet cells. Bioinformatics analysis was used to detect the lncRNA uc.322 sequence, location, and structural features. Expression of lncRNA uc.322 in different tissues was detected by quantitative polymerase chain reaction analyses. Quantitative polymerase chain reaction, Western blot analysis, adenosine triphosphate determination, glucose-stimulated insulin secretion, and enzyme-linked immunosorbent assay were used to evaluate the effects of lncRNA uc.322 on insulin secretion. The results showed that the full-length of lncRNA uc.322 is 224 bp and that it is highly conserved in various species. Bioinformatics analysis revealed that lncRNA uc.322 is located on chr7:122893196-122893419 (GRCH37/hg19) within the SRY-related HMG-box 6 gene exon region. Compared with other tissues, lncRNA uc.322 is highly expressed in pancreatic tissue. Upregulation of lncRNA uc.322 expression increases the insulin transcription factors pancreatic and duodenal homeobox 1 and Forkhead box O1 expression, promotes insulin secretion in the extracellular fluid of Min6 cells, and increases the adenosine triphosphate concentration. On the other hand, knockdown of lncRNA uc.322 has opposite effects on Min6 cells. Overall, this study showed that upregulation of lncRNA uc.322 in islet β-cells can increase the expression of insulin transcription factors and promote insulin secretion, and it may be a new therapeutic target for diabetes.

摘要

越来越多的证据表明,长链非编码 RNA(lncRNA)通过多种途径和分子机制调节基因表达,从而发挥特殊的生物学功能。本研究旨在探讨 lncRNA uc.322 在胰岛细胞中的表达特征及其对胰岛细胞分泌功能的影响。生物信息学分析用于检测 lncRNA uc.322 的序列、位置和结构特征。通过定量聚合酶链反应分析检测不同组织中 lncRNA uc.322 的表达。定量聚合酶链反应、Western blot 分析、三磷酸腺苷测定、葡萄糖刺激的胰岛素分泌和酶联免疫吸附测定用于评估 lncRNA uc.322 对胰岛素分泌的影响。结果表明,lncRNA uc.322 的全长为 224bp,在不同物种中高度保守。生物信息学分析显示,lncRNA uc.322 位于 chr7:122893196-122893419(GRCH37/hg19)上,位于 SRY 相关 HMG 盒 6 基因外显子区域内。与其他组织相比,lncRNA uc.322 在胰腺组织中高表达。lncRNA uc.322 表达上调增加了胰岛转录因子胰腺十二指肠同源盒 1 和叉头框 O1 的表达,促进了 Min6 细胞细胞外液中的胰岛素分泌,并增加了三磷酸腺苷浓度。另一方面,lncRNA uc.322 的敲低对 Min6 细胞有相反的影响。总之,本研究表明,胰岛β细胞中 lncRNA uc.322 的上调可以增加胰岛素转录因子的表达并促进胰岛素分泌,它可能是糖尿病的一个新的治疗靶点。

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