Role of microRNA-21 in the formation of insulin -producing cells from pancreatic progenitor cells

文献类型: 外文期刊

第一作者: Bai, Chunyu

作者: Bai, Chunyu;Li, Xiangchen;Gao, Yuhua;Wang, Kunfu;Fan, Yanan;Zhang, Shuang;Ma, Yuehui;Guan, Weijun

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关键词: Pancreatic progenitor cells;Insulin-producing cells;miR-21;Insulin secretion

期刊名称:BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS ( 影响因子:4.49; 五年影响因子:5.318 )

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收录情况: SCI

摘要: MicroRNAs (miRNAs) regulate insulin secretion, pancreas development, and beta cell differentiation. In this study, to screen for miRNAs and their targets that function during insulin-producing cells (IPCs) formation, we examined the messenger RNA and microRNA expression profiles of pancreatic progenitor cells (PPCs) and IPCs using micro array and deep sequencing approaches, respectively. Combining our data with that from previous reports, we found that miR-21 and its targets play an important role in the formation of IPCs. However, the function of miR-21 in the formation of IPCs from PPCs is poorly understood. Therefore, we over-expressed or inhibited miR-21 and expressed small interfering RNAs of miR-21 targets in PPCs to investigate their functions in IPCs formation. We found that miR-21 acts as a bidirectional switch in the formation of IPCs by regulating the expression of target and downstream genes (SOX6, RPBJ and HES1). Small interfering RNAs were used to knock down these genes in PPCs to investigate their effects on IPCs formation. Single expression of si-RBPJ, si-SOX6 and si-HES1 in PPCs showed that si-RBPJ was an inhibitor, and that si-SOX6 and si-HES1 were promoters of IPCs formation, although si-HES1 induced formation of IPCs at higher rates than si-SOX6. These results suggest that endogenous miRNAs involved in the formation of IPCs from PPCs should be considered in the development of an effective cell transplant therapy for diabetes. (C) 2015 Elsevier B.V. All rights reserved.

分类号: Q7

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