title: Role of microRNA-21 in the formation of insulin-producing cells from pancreatic progenitor cells.
abstract: 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 microarray 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.
authors.affiliation: Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China.
authors.forename: Chunyu
authors.initials: C
authors.lastname: Bai
authors.affiliation: Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China.
authors.forename: Xiangchen
authors.initials: X
authors.lastname: Li
authors.affiliation: Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China.
authors.forename: Yuhua
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China.
authors.forename: Kunfu
authors.initials: K
authors.lastname: Wang
authors.affiliation: Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China.
authors.forename: Yanan
authors.initials: Y
authors.lastname: Fan
authors.affiliation: Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China. Electronic address: yuehui_ma@hotmail.com.
authors.forename: Yuehui
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China. Electronic address: weijunguan301@gmail.com.
authors.forename: Weijun
authors.initials: W
authors.lastname: Guan
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000096:biosynthesis* / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D002642:Chick Embryo; D003920:Diabetes Mellitus / Q000235:genetics* / Q000473:pathology; D018507:Gene Expression Regulation, Developmental; D059014:High-Throughput Nucleotide Sequencing; D018398:Homeodomain Proteins / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D007328:Insulin / Q000235:genetics / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism / Q000473:pathology; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D055755:SOXD Transcription Factors / Q000096:biosynthesis* / Q000235:genetics; D013234:Stem Cells / Q000378:metabolism; D000072056:Transcription Factor HES-1
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D018398:Homeodomain Proteins; D007328:Insulin; D035683:MicroRNAs; D055755:SOXD Transcription Factors; D000072056:Transcription Factor HES-1; C489734:Hes1 protein, mouse; C524940:MIRN21 microRNA, human; C095939:Sox6 protein, mouse
keywords: Insulin secretion; Insulin-producing cells; Pancreatic progenitor cells; miR-21