Inflammation-Mediated Regulation of MicroRNA Expression in Transplanted Pancreatic Islets
Table 4
Genes identified as potential miRNA targets by PicTar algorithm. Genes in bold font are associated with regulation of insulin signaling and secretion, diabetes, and islet physiology.
miRNA
Genes
Description and function
miR-21
Acbd5
Crebl2
Xkr6
Pdcd4
Program cell death 4. Pdcd4 is a major transcript in in vivo pancreatic islet neogenesis [48]. Pdcd4-deficient NOD mice do not develop diabetes [49].
Arglu1
Mrpl49
Zadh2
Arhgap24
Rqcd1
Pclo
Piccolo, presynaptic cytomatrix protein. A Ca2+ sensor protein important in cAMP insulin secretion [50].
miR-98
Abcb9
Dnajc1
Msi2
Zfp462
Aldh6a1
Dusp7
Nlk
Ccnd1
Cyclin D1. Enhances human beta-cell replication and function in vivo [51].
Anapc5
Eif4g2
Npepl1
Ghr
Growth hormone receptor. Essential for maintaining pancreatic islet size and normal insulin sensitivity and glucose homeostasis [52].
Asap1
Elovl4
Ppapdc2
Gtf2i
General transcription factor II. Assists to overcome various insults and to sustain pancreatic beta-cell function [53].
Brd3
Frmd5
Robo2
Isl1
Insulin gene enhancer protein ISL-1. Role in endocrine pancreatic development [54]. Reduction in Isl1 expression results in the impairment of insulin expression [55].
Btg2
Gnptab
Rufy3
Pbx1
Pre-B-cell leukemia transcription factor 1. Development and function of pancreatic islets [56].
Bzw1
Golt1b
Sbk1
Pbx2
Pbx2-pre-B-cell leukemia transcription factor 2. Pancreatic development [57].
Cnot2
Kif2a
Son
Ppargc1b
Peroxisome-proliferative-activated receptor, gamma, coactivator 1 beta. Effect in insulin resistance and T2D [58].
Coil
Med14
Trib2
Rgs16
Regulator of G-protein signaling 16. Control aspects of islet progenitor cell activation, differentiation, and beta-cell expansion in embryos and metabolically stressed adults [59].
Dhx57
Mobkl3
Ubfd1
Vsnl1
Visinin-like protein1. A Ca2+ sensor protein that regulates insulin secretion [60].
miR-27a
Abcb9
H3f3b
Nlk
Wnk1
Ank3
Hmgcr
Obfc2a
Ypel3
Appbp2
Kbtbd8
Pank1
Ywhab
Arglu1
Kcnk2
Pde10a
Zadh2
Asph
Lpcat1
Phb
Zfp148
Btg2
Marcks
Pskh1
Zfp462
Cdc25b
Med14
Rcan2
Zhx1
Cdh11
Mrps14
Rpn2
Abca1
ATP-binding cassette, subfamily A, member 1. Influences insulin secretion and glucose homeostasis [61, 62].
Dcx
Msi2
Sbk1
Acly
ATP citrate lyase. Protects against free-fatty-acid-mediated apotosis of beta-cells [63].
Elmo1
Mycbp
Sgpp1
Bnip3l
BCL2/adenovirus E1B interacting protein 3-like. Critical mediator of β cell apoptosis and programmed necrosis in Pdx1-deficient diabetes [64].
Fbxo33
Nap1l3
Smarca1
Irs1
Insulin receptor substrate 1. Islets from IRS-1 knockout mice exhibit marked insulin secretory defects and reduced insulin expression [65].
Fubp3
Ncald
Stx16
Isl1
Described above.
Galnt5
Necap1
Tardbp
Map3k12
Mitogen-activated protein kinase kinase kinase 12. Activation of Map3k12 by cyclosporin A induces beta-cell apoptosis in posttransplant diabetes [66].
Golt1b
Nedd4
Tmtc2
Myt1
Myelin transcription factor. Myt1 is involved in proper endocrine differentiation and function [67].
Gse1
Neo1
Ubfd1
Snap25
Synaptosomal-associated protein 25. Role in exocytotic vesicle recycling and granule exocytosis in pancreatic beta-cells [68].
Gtf2i
Nf1
Usp9x
Sv2a
Synaptic vesicle protein 2. Role in Ca2+-dependent function in insulin exocytosis [69].
miR-143
Ash1l
Frmd5
Necap1
Vapb
Atp6v1a
Josd1
Ntrk2
Zfp148
Cbfb
Marcks
Ppp4r2
Cnnm3
Msi2
Tsc22d3
let-7d
Abcb9
Elovl4
Nlk
Gnaq
Guanine nucleotide binding protein. Inactivation of Gnaq resulted in impaired glucose tolerance and insulin secretion in mice [70].
Bzw1
Frmd5
Pbx1
Isl1
Described above.
Cnih
Gnptab
Ppapdc2
Pbx2
Described above.
Coil
Golt1b
Pskh1
Rgs16
Described above.
Dcaf8
Ip6k2
Robo2
Rhob
Ras homolog gene family, member B. RhoB is an early-response gene whose expression is elevated by cellular stresses. It is important for the induction of β-cell loss [71].
Dhx57
Magt1
Rufy3
Ebag9
Med14
Sdc2
Eif4g2
Myh10
Slc24a2
miR-126
Ahcyl2
Ergic2
Nf1
Slc7a5
Atp2b1
Fbxo33
Ppm1b
Spred1
Atrn
Fyttd1
Ppp1r10
Wdr47
Bcl2l2
Gnaq
Ppp4r2
Zadh2
Bet1
Gria2
Psmc6
Acsl6
acyl-CoA synthetase long-chain family member 6. It mediates the postive effect of dehydroepiandrosterone (DHEAS) on insulin secretion [72].
Bzw1
Irs1
Rbbp6
Eif4a2
Eukaryotic translation initiation factor 4A2. EIF4A2 is a positional candidate gene linked to type 2 diabetes. It is downregulated by glucose in INS1 cells [73].
Efnb1
Necap1
Rit2
miR-22
Anapc5
Ntrk2
Tmem50b
Csnk2a1
Casein kinase 1. Regulation of insulin production in islets [74].
Calm3
Nudt4
Trib2
Etv1
Ets variant 1. It is regulated by Nkx2.2 during the major wave of pancreatic endocrine and exocrine cell differentiation [75].
H3f3b
Ptprd
Vezf1
Neurod1
Neurogenic differentiation 1. Conversion of pancreatic progenitor cells into endocrine cells [76]. Contribute to beta-cell-specific and glucose-responsive insulin gene transcription [77].
Map3k12
Rgp1
Wasf1
Necap1
Sv2a
Wnk1
miR-129
Ash1l
H3f3b
Rab5b
Vps26a
Azin1
Hsph1
Rybp
Wee1
Bzw1
Itm2b
Sgms1
Zbtb44
Ctdspl2
Jag1
Slain2
Zfand3
Cxxc5
Kpna4
Slc6a6
Zfp36l1
Eif3j
Magi3
Smndc1
Crtc2
CREB-regulated transcription coactivator 2. Crtc2 is a coactivator of the cAMP response element-binding [78, 79].
Etv5
Pkia
Sp1
Mark2
MAP/microtubule affinity-regulating kinase 2. Block the Creb:Crtc2 interaction [80].
Fbxw2
Ppp1r14c
Sp3
Pten
Phosphatase and tensin homology. Deletion of Pten, a negative regulator of the P13K pathway, leads to increased β-cell mass and function [81, 82].