MicroRNA signature of the human developing pancreas.
BACKGROUND
MicroRNAs are non-coding RNAs that regulate gene expression including differentiation and development by either inhibiting translation or inducing target degradation. The aim of this study is to determine the microRNA expression signature during human pancreatic development and to identify potential microRNA gene targets calculating correlations between the signature microRNAs and their corresponding mRNA targets, predicted by bioinformatics, in genome-wide RNA microarray study.


RESULTS
The microRNA signature of human fetal pancreatic samples 10-22 weeks of gestational age (wga), was obtained by PCR-based high throughput screening with Taqman Low Density Arrays. This method led to identification of 212 microRNAs. The microRNAs were classified in 3 groups: Group number I contains 4 microRNAs with the increasing profile; II, 35 microRNAs with decreasing profile and III with 173 microRNAs, which remain unchanged. We calculated Pearson correlations between the expression profile of microRNAs and target mRNAs, predicted by TargetScan 5.1 and miRBase algorithms, using genome-wide mRNA expression data. Group I correlated with the decreasing expression of 142 target mRNAs and Group II with the increasing expression of 876 target mRNAs. Most microRNAs correlate with multiple targets, just as mRNAs are targeted by multiple microRNAs. Among the identified targets are the genes and transcription factors known to play an essential role in pancreatic development.


CONCLUSIONS
We have determined specific groups of microRNAs in human fetal pancreas that change the degree of their expression throughout the development. A negative correlative analysis suggests an intertwined network of microRNAs and mRNAs collaborating with each other. This study provides information leading to potential two-way level of combinatorial control regulating gene expression through microRNAs targeting multiple mRNAs and, conversely, target mRNAs regulated in parallel by other microRNAs as well. This study may further the understanding of gene expression regulation in the human developing pancreas.
Rosero
Samuel
S
Diabetes Research Institute, University of Miami, Miller School of Medicine, Miami, FL 33136, USA.
Bravo-Egana
Valia
V
Jiang
Zhijie
Z
Khuri
Sawsan
S
Tsinoremas
Nicholas
N
Klein
Dagmar
D
Sabates
Eduardo
E
Correa-Medina
Mayrin
M
Ricordi
Camillo
C
Domínguez-Bendala
Juan
J
Diez
Juan
J
Pastori
Ricardo L
RL
D000465:Algorithms; D005260:Female; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D035683:MicroRNAs / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D010179:Pancreas / Q000196:embryology* / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D035683:MicroRNAs; D012333:RNA, Messenger