title: Systematic profiling of mRNA and miRNA expression in the pancreatic islets of spontaneously diabetic Goto-Kakizaki rats.
abstract: Type 2 diabetes (T2DM) is a complex multifactorial metabolic disorder that affects >100 million individuals worldwide, yet the mechanisms involved in the development and progression of the disease have not yet been fully elucidated. The present study examined the mRNA and micro (mi)RNA expression profiles by microarray analysis in the pancreas islets of spontaneously diabetic Goto-Kakizaki rats with the aim to identify regulatory mechanisms underlying the pathogenesis of T2DM. A total of 9 upregulated and 10 downregulated miRNAs were identified, including miR-150, miR-497, miR-344-3p and let-7f, which were independently validated by quantitative polymerase chain reaction assays. In addition, differential expression of 670 genes was detected by mRNA microarray analysis, including 370 upregulated and 247 downregulated genes. The differentially expressed genes were statistically associated with major cellular pathways, including the immune response pathway and the extracellular matrix (ECM)-receptor interaction pathway. Finally, a reverse regulatory association of differentially expressed miRNAs and their predicted target genes was constructed, supported by analysis of their mRNA and miRNA expression profiles. A number of key pairs of miRNA-mRNA was proposed to have significant roles in the pathogenesis of T2DM rats based on bioinformatics analysis, one example being the let-7f/collagen, type II, alpha 1 pair that may regulate ECM-receptor interactions.
authors.affiliation: Medical Systems Biology Research Center, Tsinghua University School of Medicine, Beijing 100084, P.R. China.
authors.forename: Ling-Qin
authors.initials: LQ
authors.lastname: Zeng
authors.affiliation: Medical Systems Biology Research Center, Tsinghua University School of Medicine, Beijing 100084, P.R. China.
authors.forename: Su-Bi
authors.initials: SB
authors.lastname: Wei
authors.affiliation: National Engineering Research Center for Beijing Biochip Technology, Beijing 102206, P.R. China.
authors.forename: Yi-Min
authors.initials: YM
authors.lastname: Sun
authors.affiliation: National Engineering Research Center for Beijing Biochip Technology, Beijing 102206, P.R. China.
authors.forename: Wen-Yan
authors.initials: WY
authors.lastname: Qin
authors.affiliation: Medical Systems Biology Research Center, Tsinghua University School of Medicine, Beijing 100084, P.R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Cheng
authors.affiliation: National Engineering Research Center for Beijing Biochip Technology, Beijing 102206, P.R. China.
authors.forename: Keith
authors.initials: K
authors.lastname: Mitchelson
authors.affiliation: Medical Systems Biology Research Center, Tsinghua University School of Medicine, Beijing 100084, P.R. China.
authors.forename: Lan
authors.initials: L
authors.lastname: Xie
mesh_terms: D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D007515:Islets of Langerhans / Q000378:metabolism* / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics*; D051381:Rats; D015203:Reproducibility of Results
chemical_list: D035683:MicroRNAs; D012333:RNA, Messenger