Accession ID: MIRT005117 [miRNA, hsa-miR-125a-5p :: ERBB3, target gene]
pre-miRNA Information
pre-miRNA ID hsa-mir-125aLinkOut: [miRBase ]
Description Homo sapiens miR-125a stem-loop
Comment This miRNA sequence is predicted based on homology to a verified miRNA from mouse .
2nd Structure of pre-miRNA
Disease
Mature miRNA Information
Mature miRNA hsa-miR-125a-5p
Mature Sequence 15| UCCCUGAGACCCUUUAACCUGUGA |38
Evidence Experimental
Experiments Cloned
Putative hsa-miR-125a-5p Targets LinkOut: [ TargetScanS 5.1 | MicroCosm | microRNA.org | miRecords | miRDB | miRo | miRNAMap 2.0 ]
Gene Information
Gene Symbol ERBB3 LinkOut: [ Entrez Gene | BioGPS | Wikipedia | iHop ]
Synonyms ErbB-3, HER3, LCCS2, MDA-BF-1, MGC88033, c-erbB-3, c-erbB3, erbB3-S, p180-ErbB3, p45-sErbB3, p85-sErbB3
Description v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (avian)
Transcript NM_0019    LinkOut: [ RefSeq ]
Other Transcripts NM_0010059   
Expression LinkOut: [ BioGPS ]
Putative miRNA Targets on ERBB3 LinkOut: [ TargetScan 5.1 | MicroCosm | miRNAMap 2.0 ]
3'UTR of ERBB3
(miRNA target sites are highlighted)
>ERBB3|NM_0019|3'UTR
   1 TAACTCCTGCTCCCTGTGGCACTCAGGGAGCATTTAATGGCAGCTAGTGCCTTTAGAGGGTACCGTCTTCTCCCTATTCC
  81 CTCTCTCTCCCAGGTCCCAGCCCCTTTTCCCCAGTCCCAGACAATTCCATTCAATCTTTGGAGGCTTTTAAACATTTTGA
 161 CACAAAATTCTTATGGTATGTAGCCAGCTGTGCACTTTCTTCTCTTTCCCAACCCCAGGAAAGGTTTTCCTTATTTTGTG
 241 TGCTTTCCCAGTCCCATTCCTCAGCTTCTTCACAGGCACTCCTGGAGATATGAAGGATTACTCTCCATATCCCTTCCTCT
 321 CAGGCTCTTGACTACTTGGAACTAGGCTCTTATGTGTGCCTTTGTTTCCCATCAGACTGTCAAGAAGAGGAAAGGGAGGA
 401 AACCTAGCAGAGGAAAGTGTAATTTTGGTTTATGACTCTTAACCCCCTAGAAAGACAGAAGCTTAAAATCTGTGAAGAAA
 481 GAGGTTAGGAGTAGATATTGATTACTATCATAATTCAGCACTTAACTATGAGCCAGGCATCATACTAAACTTCACCTACA
 561 TTATCTCACTTAGTCCTTTATCATCCTTAAAACAATTCTGTGACATACATATTATCTCATTTTACACAAAGGGAAGTCGG
 641 GCATGGTGGCTCATGCCTGTAATCTCAGCACTTTGGGAGGCTGAGGCAGAAGGATTACCTGAGGCAAGGAGTTTGAGACC
 721 AGCTTAGCCAACATAGTAAGACCCCCATCTCTTTAAAAAAAAAAAAAAAAAAAAAAAAAAAACTTTAGAACTGGGTGCAG
 801 TGGCTCATGCCTGTAATCCCAGCCAGCACTTTGGGAGGCTGAGATGGGAAGATCACTTGAGCCCAGAATTAGAGATAAGC
 881 CTATGGAAACATAGCAAGACACTGTCTCTACAGGGGAAAAAAAAAAAAGAAACTGAGCCTTAAAGAGATGAAATAAATTA
 961 AGCAGTAGATCCAGGATGCAAAATCCTCCCAATTCCTGTGCATGTGCTCTTATTGTAAGGTGCCAAGAAAAACTGATTTA
1041 AGTTACAGCCCTTGTTTAAGGGGCACTGTTTCTTGTTTTTGCACTGAATCAAGTCTAACCCCAACAGCCACATCCTCCTA
1121 TACCTAGACATCTCATCTCAGGAAGTGGTGGTGGGGGTAGTCAGAAGGAAAAATAACTGGACATCTTTGTGTAAACCATA
1201 ATCCACATGTGCCGTAAATGATCTTCACTCCTTATCCGAGGGCAAATTCACAAGGATCCCCAAGATCCACTTTTAGAAGC
1281 CATTCTCATCCA
Target sites Provided by authors  Predicted by miRanda
miRNA-target interactions (Predicted by miRanda)
IDDuplex structurePositionScoreMFE
1
miRNA  3' aguguccaauuuCCCAGAGUCCCu 5'
                      ||  ||||||| 
Target 5' cctgctccctgtGGCACTCAGGGa 3'
6 - 29 144.00 -14.70
2
miRNA  3' aguguccaauuucccAGAGUCCcu 5'
                         |||||||  
Target 5' ctccatatcccttccTCTCAGGct 3'
303 - 326 125.00 -8.87
3
miRNA  3' aguguccaauuucccAGAGUCCcu 5'
                         |||||||  
Target 5' tacctagacatctcaTCTCAGGaa 3'
1121 - 1144 125.00 -9.43
Experimental Support 1 for Functional miRNA-Target Interaction
miRNA:Target hsa-miR-125a-5p :: ERBB3    [ Functional MTI ]
Validation Method Luciferase reporter assay , Northern blot , qRT-PCR , Western blot , Other
Conditions SKBR3 , MCF10A
Location of target site 3'UTR
Original Description (Extracted from the article) ... Using the human breast cancer cell line SKBR3 as a model for ERBB2 and ERBB3 dependence, infection of these cells with retroviral constructs expressing either miR-125a or miR-125b resulted in suppression of ERBB2 and ERBB3 at both the transcript and protein level. Luciferase constructs containing the 3' 3'-untranslated regions of ERBB2 and ERBB3 demonstrated 35% less activity in miR-125a- and miR-125b-expressing cells relative to controls. ...

- Scott, G. K. Goga, A. Bhaumik, D. Berger, et al., 2007, J Biol Chem.

Article - Scott, G. K. Goga, A. Bhaumik, D. Berger, et al.
- J Biol Chem, 2007
Deregulation of micro-RNAs (miRNAs) is emerging as a major aspect of cancer etiology because their capacity to direct the translation and stability of targeted transcripts can dramatically influence cellular physiology. To explore the potential of exogenously applied miRNAs to suppress oncogenic proteins, the ERBB oncogene family was chosen with a bioinformatics search identifying targeting seed sequences for miR-125a and miR-125b within the 3'-untranslated regions of both ERBB2 and ERBB3. Using the human breast cancer cell line SKBR3 as a model for ERBB2 and ERBB3 dependence, infection of these cells with retroviral constructs expressing either miR-125a or miR-125b resulted in suppression of ERBB2 and ERBB3 at both the transcript and protein level. Luciferase constructs containing the 3' 3'-untranslated regions of ERBB2 and ERBB3 demonstrated approximately 35% less activity in miR-125a- and miR-125b-expressing cells relative to controls. Additionally, phosphorylation of ERK1/2 and AKT was suppressed in SKBR3 cells overexpressing either miR-125a or miR-125b. Consistent with suppression of both ERBB2 and ERBB3 signaling, miR-125a-or miR-125b-overexpressing SKBR3 cells were impaired in their anchorage-dependent growth and exhibited reduced migration and invasion capacities. Parallel studies performed on MCF10A cells demonstrated that miR-125a or miR-125b overexpression produced only marginal influences on the growth and migration of these non-transformed human mammary epithelial cells. These results illustrate the feasibility of using miRNAs as a therapeutic strategy to suppress oncogene expression and function.
LinkOut: [PMID: 17110380]
Experimental Support 2 for Functional miRNA-Target Interaction
miRNA:Target hsa-miR-125a-5p :: ERBB3    [ Functional MTI ]
Validation Method Luciferase reporter assay , Microarray , Western blot
Conditions SKBB3 , Raf1 , A549
Location of target site 3'UTR
Tools used in this research TargetScan
Original Description (Extracted from the article) ... The importance of miRNAs not only as regulators but also as effectors of ErbB signalling is emphasized by miR-21, a key mediator of cancer cell growth and invasion whose expression is stimulated by EGFR/ErbB2. Studies are underway to modulate miRNA expression and activity in vivo with a view to developing therapeutics that can effectively block signalling pathways critical to tumour development and progression, although technical hurdles relating to delivery and tissue specificity are still to be overcome. As high-throughput miRNA profiling becomes feasible, a major goal is the identification of miRNA signatures that are predictive of treatment response, clinical outcome, or that can stratify tumour phenotypes. Should recent advances in understanding the basic science of miRNAs in cancer be translated to the clinic then there is the potential that they will transform cancer diagnosis and treatment. ...

- Barker, A. Giles, K. M. Epis, M. R. Zhang, et al., 2010, Curr Opin Pharmacol.

Article - Barker, A. Giles, K. M. Epis, M. R. Zhang, et al.
- Curr Opin Pharmacol, 2010
Recent years have seen a massive expansion in our understanding of the biology of microRNAs (miRNAs) in cancer, through the identification of miRNAs with aberrant expression in specific cancers and the functional validation of their critical target molecules and cellular effects. In parallel, targeted therapeutic agents to block signalling pathways critical to tumour growth and progression have been developed but have yielded disappointing clinical results. The discovery of miRNAs that regulate ErbB signalling in cancer cells brings new hope that in the future these oncogenic pathways can be more effectively inhibited to improve patient outcomes.
LinkOut: [PMID: 20864407]
Experimental Support 3 for Functional miRNA-Target Interaction
miRNA:Target hsa-miR-125a-5p :: ERBB3    [ Functional MTI ]
Validation Method Other
Article - Le, M. T. Shyh-Chang, N. Khaw, S. L. Chin, et al.
- PLoS Genet, 2011
MicroRNAs regulate networks of genes to orchestrate cellular functions. MiR-125b, the vertebrate homologue of the Caenorhabditis elegans microRNA lin-4, has been implicated in the regulation of neural and hematopoietic stem cell homeostasis, analogous to how lin-4 regulates stem cells in C. elegans. Depending on the cell context, miR-125b has been proposed to regulate both apoptosis and proliferation. Because the p53 network is a central regulator of both apoptosis and proliferation, the dual roles of miR-125b raise the question of what genes in the p53 network might be regulated by miR-125b. By using a gain- and loss-of-function screen for miR-125b targets in humans, mice, and zebrafish and by validating these targets with the luciferase assay and a novel miRNA pull-down assay, we demonstrate that miR-125b directly represses 20 novel targets in the p53 network. These targets include both apoptosis regulators like Bak1, Igfbp3, Itch, Puma, Prkra, Tp53inp1, Tp53, Zac1, and also cell-cycle regulators like cyclin C, Cdc25c, Cdkn2c, Edn1, Ppp1ca, Sel1l, in the p53 network. We found that, although each miRNA-target pair was seldom conserved, miR-125b regulation of the p53 pathway is conserved at the network level. Our results lead us to propose that miR-125b buffers and fine-tunes p53 network activity by regulating the dose of both proliferative and apoptotic regulators, with implications for tissue stem cell homeostasis and oncogenesis.
LinkOut: [PMID: 21935352]
MiRNA-Target Expression Profile:

 
MiRNA-Target Interaction Network:
Strong evidence (reporter assay, western blot, qRT-PCR or qPCR)
Other evidence
138 hsa-miR-125a-5p Target Genes:
ID Target Description Validation methods
Strong evidence Less strong evidence
MIRT000602 CDKN1A cyclin-dependent kinase inhibitor 1A (p21, Cip1) 4 1
MIRT003738 LIN28A lin-28 homolog A (C. elegans) 2 2
MIRT003755 NTRK3 neurotrophic tyrosine kinase, receptor, type 3 3 5
MIRT004052 CD34 CD34 molecule 4 1
MIRT004071 TP53 tumor protein p53 4 2
MIRT004326 LIF leukemia inhibitory factor (cholinergic differentiation factor) 1 1
MIRT004388 MTUS1 microtubule associated tumor suppressor 1 2 1
MIRT004389 RARA retinoic acid receptor, alpha 2 1
MIRT004445 VEGFA vascular endothelial growth factor A 2 1
MIRT005117 ERBB3 v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (avian) 5 3
MIRT005118 ERBB2 v-erb-b2 erythroblastic leukemia viral oncogene homolog 2, neuro/glioblastoma derived oncogene homolog (avian) 4 3
MIRT005339 KLF13 Kruppel-like factor 13 4 1
MIRT005350 BAK1 BCL2-antagonist/killer 1 4 1
MIRT005419 ARID3B AT rich interactive domain 3B (BRIGHT-like) 3 1
MIRT005421 ELAVL1 ELAV (embryonic lethal, abnormal vision, Drosophila)-like 1 (Hu antigen R) 3 1
MIRT005678 CCL5 chemokine (C-C motif) ligand 5 0 1
MIRT006471 TNFAIP3 tumor necrosis factor, alpha-induced protein 3 2 1
MIRT006809 SMAD4 SMAD family member 4 2 1
MIRT006905 MMP11 matrix metallopeptidase 11 (stromelysin 3) 3 1
MIRT006944 HK2 hexokinase 2 1 1
MIRT021283 ARPC5 actin related protein 2/3 complex, subunit 5, 16kDa 1 1
MIRT021284 E2F7 E2F transcription factor 7 1 1
MIRT021285 ZBTB10 zinc finger and BTB domain containing 10 1 1
MIRT021286 CREB5 cAMP responsive element binding protein 5 1 1
MIRT021287 OMA1 OMA1 homolog, zinc metallopeptidase (S. cerevisiae) 1 1
MIRT021288 OSTM1 osteopetrosis associated transmembrane protein 1 1 1
MIRT021289 MAPK8 mitogen-activated protein kinase 8 1 1
MIRT021290 RBM17 RNA binding motif protein 17 1 1
MIRT021291 PUM2 pumilio homolog 2 (Drosophila) 1 1
MIRT021292 NR1D2 nuclear receptor subfamily 1, group D, member 2 1 1
MIRT021293 HOXC4 homeobox C4 1 1
MIRT021294 SNX4 sorting nexin 4 1 1
MIRT021295 NDUFB6 NADH dehydrogenase (ubiquinone) 1 beta subcomplex, 6, 17kDa 1 1
MIRT021296 NOP16 NOP16 nucleolar protein homolog (yeast) 1 1
MIRT021297 CRK v-crk sarcoma virus CT10 oncogene homolog (avian) 1 1
MIRT021298 SLC1A5 solute carrier family 1 (neutral amino acid transporter), member 5 1 1
MIRT021299 PARD6B par-6 partitioning defective 6 homolog beta (C. elegans) 1 1
MIRT021300 TCEB2 transcription elongation factor B (SIII), polypeptide 2 (18kDa, elongin B) 1 1
MIRT021301 PANX1 pannexin 1 1 1
MIRT021302 ZFAND1 zinc finger, AN1-type domain 1 1 1
MIRT021303 CORO1C coronin, actin binding protein, 1C 1 1
MIRT021304 CLDN12 claudin 12 1 1
MIRT021305 ZNF776 zinc finger protein 776 1 1
MIRT021306 TNPO2 transportin 2 1 1
MIRT021307 EIF4EBP1 eukaryotic translation initiation factor 4E binding protein 1 1 1
MIRT021308 PDPK1 3-phosphoinositide dependent protein kinase-1 1 1
MIRT021309 YES1 v-yes-1 Yamaguchi sarcoma viral oncogene homolog 1 1 2
MIRT021310 DUSP3 dual specificity phosphatase 3 1 1
MIRT021311 YOD1 YOD1 OTU deubiquinating enzyme 1 homolog (S. cerevisiae) 1 1
MIRT021312 ATXN1 ataxin 1 1 1
MIRT021313 TMEM101 transmembrane protein 101 1 1
MIRT021314 ERMP1 endoplasmic reticulum metallopeptidase 1 1 1
MIRT021315 GUCD1 chromosome 22 open reading frame 13 1 1
MIRT021316 RBAK RB-associated KRAB zinc finger 1 1
MIRT021317 ATL2 atlastin GTPase 2 1 1
MIRT045697 OGT O-linked N-acetylglucosamine (GlcNAc) transferase (UDP-N-acetylglucosamine:polypeptide-N-acetylglucosaminyl transferase) 1 1
MIRT045698 PREPL prolyl endopeptidase-like 1 1
MIRT045699 PPP2R5E protein phosphatase 2, regulatory subunit B', epsilon isoform 1 1
MIRT045700 TFRC transferrin receptor (p90, CD71) 1 1
MIRT045701 G2E3 G2/M-phase specific E3 ubiquitin ligase 1 1
MIRT045702 PLS3 plastin 3 1 1
MIRT045703 TTC30B tetratricopeptide repeat domain 30B 1 1
MIRT045704 RRP1B ribosomal RNA processing 1 homolog B (S. cerevisiae) 1 1
MIRT045705 COIL coilin 1 1
MIRT045706 NDEL1 nudE nuclear distribution gene E homolog (A. nidulans)-like 1 1 1
MIRT045707 ATXN7L3 ataxin 7-like 3 1 1
MIRT045708 PRC1 protein regulator of cytokinesis 1 1 1
MIRT045709 LIN28B lin-28 homolog B (C. elegans) 1 1
MIRT045710 TOR1AIP2 torsin A interacting protein 2 1 1
MIRT045711 KIAA0232 KIAA0232 1 1
MIRT045712 TOR4A chromosome 9 open reading frame 167 1 1
MIRT045713 TPI1 triosephosphate isomerase 1 1 1
MIRT045714 PCDHGB2 protocadherin gamma subfamily B, 2 1 1
MIRT045715 UBE2G2 ubiquitin-conjugating enzyme E2G 2 (UBC7 homolog, yeast) 1 1
MIRT045716 SPRTN chromosome 1 open reading frame 124 1 1
MIRT045717 XPO1 exportin 1 (CRM1 homolog, yeast) 1 1
MIRT045718 THRAP3 thyroid hormone receptor associated protein 3 1 1
MIRT045719 OSBPL9 oxysterol binding protein-like 9 1 1
MIRT045720 LBX2 ladybird homeobox 2 1 1
MIRT045721 SEPW1 selenoprotein W, 1 1 1
MIRT045722 PGM3 phosphoglucomutase 3 1 1
MIRT045723 MACF1 microtubule-actin crosslinking factor 1 1 1
MIRT045724 PC pyruvate carboxylase 1 1
MIRT045725 EEF1A1 eukaryotic translation elongation factor 1 alpha 1 1 1
MIRT045726 TBC1D1 TBC1 (tre-2/USP6, BUB2, cdc16) domain family, member 1 1 1
MIRT045727 PLA2G4F phospholipase A2, group IVF 1 1
MIRT045728 PEG10 paternally expressed 10 1 1
MIRT045729 ATP5G2 ATP synthase, H+ transporting, mitochondrial Fo complex, subunit C2 (subunit 9) 1 1
MIRT045730 FBXO10 F-box protein 10 1 1
MIRT045731 TDG thymine-DNA glycosylase 1 1
MIRT045732 SP1 Sp1 transcription factor 1 1
MIRT045733 DLST dihydrolipoamide S-succinyltransferase (E2 component of 2-oxo-glutarate complex) 1 1
MIRT045734 WNK3 WNK lysine deficient protein kinase 3 1 1
MIRT045735 RALBP1 ralA binding protein 1 1 1
MIRT045736 RPS2 ribosomal protein S2 1 1
MIRT045737 MRPL50 mitochondrial ribosomal protein L50 1 1
MIRT045738 NIN ninein (GSK3B interacting protein) 1 1
MIRT045739 MORC2 MORC family CW-type zinc finger 2 1 1
MIRT045740 ZZEF1 zinc finger, ZZ-type with EF-hand domain 1 1 1
MIRT045741 PDCL3 phosducin-like 3 1 1
MIRT045742 RPL35A ribosomal protein L35a 1 1
MIRT045743 ND6 NADH dehydrogenase, subunit 6 (complex I) 1 1
MIRT045744 TPM4 tropomyosin 4 1 1
MIRT045745 RPL9 ribosomal protein L9 1 1
MIRT045746 ENO1 enolase 1, (alpha) 1 1
MIRT045747 CLCN7 chloride channel 7 1 1
MIRT045748 COL4A1 collagen, type IV, alpha 1 1 1
MIRT045749 NME2 non-metastatic cells 2, protein (NM23B) expressed in 1 1
MIRT045750 GGCT gamma-glutamylcyclotransferase 1 1
MIRT045751 CGNL1 cingulin-like 1 1 1
MIRT045752 ZMYND19 zinc finger, MYND-type containing 19 1 1
MIRT045753 MAT2A methionine adenosyltransferase II, alpha 1 1
MIRT045754 NPM1 nucleophosmin (nucleolar phosphoprotein B23, numatrin) 1 1
MIRT045755 NNT nicotinamide nucleotide transhydrogenase 1 1
MIRT045756 SRGAP2 SLIT-ROBO Rho GTPase activating protein 2 1 1
MIRT045757 EMID1 EMI domain containing 1 1 1
MIRT045758 ATP5J2 ATP synthase, H+ transporting, mitochondrial Fo complex, subunit F2 1 1
MIRT045759 STAT2 signal transducer and activator of transcription 2, 113kDa 1 1
MIRT045760 FERMT1 fermitin family homolog 1 (Drosophila) 1 1
MIRT045761 DIP2A DIP2 disco-interacting protein 2 homolog A (Drosophila) 1 1
MIRT045762 MAP3K1 mitogen-activated protein kinase kinase kinase 1 1 1
MIRT045763 SLFN11 schlafen family member 11 1 1
MIRT045764 AGTRAP angiotensin II receptor-associated protein 1 1
MIRT045765 KIF6 kinesin family member 6 1 1
MIRT045766 TRMT2A TRM2 tRNA methyltransferase 2 homolog A (S. cerevisiae) 1 1
MIRT045767 PAM peptidylglycine alpha-amidating monooxygenase 1 1
MIRT045768 UNC45A unc-45 homolog A (C. elegans) 1 1
MIRT045769 MAP2K7 mitogen-activated protein kinase kinase 7 1 1
MIRT045770 LYPLA1 lysophospholipase I 1 1
MIRT045771 LAMB1 laminin, beta 1 1 1
MIRT045772 NCKIPSD NCK interacting protein with SH3 domain 1 1
MIRT045773 OTUB2 OTU domain, ubiquitin aldehyde binding 2 1 1
MIRT045774 CASC4 cancer susceptibility candidate 4 1 1
MIRT045775 ZDHHC9 zinc finger, DHHC-type containing 9 1 1
MIRT045776 ARHGAP12 Rho GTPase activating protein 12 1 1
MIRT045777 YIPF4 Yip1 domain family, member 4 1 1
MIRT045778 IP6K1 inositol hexakisphosphate kinase 1 1 1
MIRT045779 C17orf80 chromosome 17 open reading frame 80 1 1