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.

miRNAGenesDescription and function

miR-21 Acbd5Crebl2Xkr6Pdcd4Program cell death 4. Pdcd4 is a major transcript in in vivo pancreatic islet neogenesis [48]. Pdcd4-deficient NOD mice do not develop diabetes [49].
Arglu1Mrpl49Zadh2
Arhgap24Rqcd1PcloPiccolo, presynaptic cytomatrix protein. A Ca2+ sensor protein important in cAMP insulin secretion [50].

miR-98 Abcb9Dnajc1Msi2Zfp462
Aldh6a1Dusp7NlkCcnd1Cyclin D1. Enhances human beta-cell replication and function in vivo [51].
Anapc5Eif4g2Npepl1GhrGrowth hormone receptor. Essential for maintaining pancreatic islet size and normal insulin sensitivity and glucose homeostasis [52].
Asap1Elovl4Ppapdc2Gtf2iGeneral transcription factor II. Assists to overcome various insults and to sustain pancreatic beta-cell function [53].
Brd3Frmd5Robo2Isl1Insulin gene enhancer protein ISL-1. Role in endocrine pancreatic development [54]. Reduction in Isl1 expression results in the impairment of insulin expression [55].
Btg2GnptabRufy3Pbx1Pre-B-cell leukemia transcription factor 1. Development and function of pancreatic islets [56].
Bzw1Golt1bSbk1Pbx2Pbx2-pre-B-cell leukemia transcription factor 2. Pancreatic development [57].
Cnot2Kif2aSonPpargc1bPeroxisome-proliferative-activated receptor, gamma, coactivator 1 beta. Effect in insulin resistance and T2D [58].
CoilMed14Trib2Rgs16Regulator of G-protein signaling 16. Control aspects of islet progenitor cell activation, differentiation, and beta-cell expansion in embryos and metabolically stressed adults [59].
Dhx57Mobkl3Ubfd1Vsnl1Visinin-like protein1. A Ca2+ sensor protein that regulates insulin secretion [60].

miR-27a Abcb9H3f3bNlkWnk1
Ank3HmgcrObfc2aYpel3
Appbp2Kbtbd8Pank1Ywhab
Arglu1Kcnk2Pde10aZadh2
AsphLpcat1PhbZfp148
Btg2MarcksPskh1Zfp462
Cdc25bMed14Rcan2Zhx1
Cdh11Mrps14Rpn2Abca1ATP-binding cassette, subfamily A, member 1. Influences insulin secretion and glucose homeostasis [61, 62].
DcxMsi2Sbk1AclyATP citrate lyase. Protects against free-fatty-acid-mediated apotosis of beta-cells [63].
Elmo1MycbpSgpp1Bnip3lBCL2/adenovirus E1B interacting protein 3-like. Critical mediator of β cell apoptosis and programmed necrosis in Pdx1-deficient diabetes [64].
Fbxo33Nap1l3Smarca1Irs1Insulin receptor substrate 1. Islets from IRS-1 knockout mice exhibit marked insulin secretory defects and reduced insulin expression [65].
Fubp3NcaldStx16Isl1Described above.
Galnt5Necap1TardbpMap3k12Mitogen-activated protein kinase kinase kinase 12. Activation of Map3k12 by cyclosporin A induces beta-cell apoptosis in posttransplant diabetes [66].
Golt1bNedd4Tmtc2Myt1Myelin transcription factor. Myt1 is involved in proper endocrine differentiation and function [67].
Gse1Neo1Ubfd1Snap25Synaptosomal-associated protein 25. Role in exocytotic vesicle recycling and granule exocytosis in pancreatic beta-cells [68].
Gtf2iNf1Usp9xSv2aSynaptic vesicle protein 2. Role in Ca2+-dependent function in insulin exocytosis [69].

miR-143 Ash1lFrmd5Necap1Vapb
Atp6v1aJosd1Ntrk2Zfp148
CbfbMarcksPpp4r2
Cnnm3Msi2Tsc22d3

let-7d Abcb9Elovl4NlkGnaqGuanine nucleotide binding protein. Inactivation of Gnaq resulted in impaired glucose tolerance and insulin secretion in mice [70].
Bzw1Frmd5Pbx1Isl1Described above.
CnihGnptabPpapdc2Pbx2Described above.
CoilGolt1bPskh1Rgs16Described above.
Dcaf8Ip6k2Robo2RhobRas 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].
Dhx57Magt1Rufy3
Ebag9Med14Sdc2
Eif4g2Myh10Slc24a2

miR-126 Ahcyl2Ergic2Nf1Slc7a5
Atp2b1Fbxo33Ppm1bSpred1
AtrnFyttd1Ppp1r10Wdr47
Bcl2l2GnaqPpp4r2Zadh2
Bet1Gria2Psmc6Acsl6acyl-CoA synthetase long-chain family member 6. It mediates the postive effect of dehydroepiandrosterone (DHEAS) on insulin secretion [72].
Bzw1Irs1Rbbp6Eif4a2Eukaryotic translation initiation factor 4A2. EIF4A2 is a positional candidate gene linked to type 2 diabetes. It is downregulated by glucose in INS1 cells [73].
Efnb1Necap1Rit2

miR-22 Anapc5Ntrk2Tmem50bCsnk2a1Casein kinase 1. Regulation of insulin production in islets [74].
Calm3Nudt4Trib2Etv1Ets variant 1. It is regulated by Nkx2.2 during the major wave of pancreatic endocrine and exocrine cell differentiation [75].
H3f3bPtprdVezf1Neurod1Neurogenic differentiation 1. Conversion of pancreatic progenitor cells into endocrine cells [76]. Contribute to beta-cell-specific and glucose-responsive insulin gene transcription [77].
Map3k12Rgp1Wasf1
Necap1Sv2aWnk1

miR-129 Ash1lH3f3bRab5bVps26a
Azin1Hsph1RybpWee1
Bzw1Itm2bSgms1Zbtb44
Ctdspl2Jag1Slain2Zfand3
Cxxc5Kpna4Slc6a6Zfp36l1
Eif3jMagi3Smndc1Crtc2CREB-regulated transcription coactivator 2. Crtc2 is a coactivator of the cAMP response element-binding [78, 79].
Etv5PkiaSp1Mark2MAP/microtubule affinity-regulating kinase 2. Block the Creb:Crtc2 interaction [80].
Fbxw2Ppp1r14cSp3PtenPhosphatase and tensin homology. Deletion of Pten, a negative regulator of the P13K pathway, leads to increased β-cell mass and function [81, 82].
GmfbRab21TiparpTiam1T-cell lymphoma invasion and metastasis 1. Tiam1 negatively affect glucose-stimulated insulin secretion [83].