Accession ID: MIRT001920 [miRNA, hsa-miR-146a-5p :: BRCA1, target gene]
pre-miRNA Information
pre-miRNA ID hsa-mir-146aLinkOut: [miRBase ]
Synonyms MIRN146, MIRN146A, miR-146a, miRNA146A, MIR146A
Description Homo sapiens miR-146a 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-146a-5p
Mature Sequence 21| UGAGAACUGAAUUCCAUGGGUU |42
Evidence Experimental
Experiments Cloned
Putative hsa-miR-146a-5p Targets LinkOut: [ TargetScanS 5.1 | MicroCosm | microRNA.org | miRecords | miRDB | miRo | miRNAMap 2.0 ]
Gene Information
Gene Symbol BRCA1 LinkOut: [ Entrez Gene | BioGPS | Wikipedia | iHop ]
Synonyms BRCAI, BRCC1, BROVCA1, IRIS, PNCA4, PSCP, RNF53
Description breast cancer 1, early onset
Transcript NM_0072    LinkOut: [ RefSeq ]
Other Transcripts NM_0072 , NM_0072 , NM_0072 , NM_0073   
Expression LinkOut: [ BioGPS ]
Putative miRNA Targets on BRCA1 LinkOut: [ TargetScan 5.1 | MicroCosm | miRNAMap 2.0 ]
3'UTR of BRCA1
(miRNA target sites are highlighted)
>BRCA1|NM_0072|3'UTR
   1 TGAGGCACCTGTGGTGACCCGAGAGTGGGTGTTGGACAGTGTAGCACTCTACCAGTGCCAGGAGCTGGACACCTACCTGA
  81 TACCCCAGATCCCCCACAGCCACTACTGACTGCAGCCAGCCACAGGTACAGAGCCACAGGACCCCAAGAATGAGCTTACA
 161 AAGTGGCCTTTCCAGGCCCTGGGAGCTCCTCTCACTCTTCAGTCCTTCTACTGTCCTGGCTACTAAATATTTTATGTACA
 241 TCAGCCTGAAAAGGACTTCTGGCTATGCAAGGGTCCCTTAAAGATTTTCTGCTTGAAGTCTCCCTTGGAAATCTGCCATG
 321 AGCACAAAATTATGGTAATTTTTCACCTGAGAAGATTTTAAAACCATTTAAACGCCACCAATTGAGCAAGATGCTGATTC
 401 ATTATTTATCAGCCCTATTCTTTCTATTCAGGCTGTTGTTGGCTTAGGGCTGGAAGCACAGAGTGGCTTGGCCTCAAGAG
 481 AATAGCTGGTTTCCCTAAGTTTACTTCTCTAAAACCCTGTGTTCACAAAGGCAGAGAGTCAGACCCTTCAATGGAAGGAG
 561 AGTGCTTGGGATCGATTATGTGACTTAAAGTCAGAATAGTCCTTGGGCAGTTCTCAAATGTTGGAGTGGAACATTGGGGA
 641 GGAAATTCTGAGGCAGGTATTAGAAATGAAAAGGAAACTTGAAACCTGGGCATGGTGGCTCACGCCTGTAATCCCAGCAC
 721 TTTGGGAGGCCAAGGTGGGCAGATCACTGGAGGTCAGGAGTTCGAAACCAGCCTGGCCAACATGGTGAAACCCCATCTCT
 801 ACTAAAAATACAGAAATTAGCCGGTCATGGTGGTGGACACCTGTAATCCCAGCTACTCAGGTGGCTAAGGCAGGAGAATC
 881 ACTTCAGCCCGGGAGGTGGAGGTTGCAGTGAGCCAAGATCATACCACGGCACTCCAGCCTGGGTGACAGTGAGACTGTGG
 961 CTCAAAAAAAAAAAAAAAAAAAGGAAAATGAAACTAGAAGAGATTTCTAAAAGTCTGAGATATATTTGCTAGATTTCTAA
1041 AGAATGTGTTCTAAAACAGCAGAAGATTTTCAAGAACCGGTTTCCAAAGACAGTCTTCTAATTCCTCATTAGTAATAAGT
1121 AAAATGTTTATTGTTGTAGCTCTGGTATATAATCCATTCCTCTTAAAATATAAGACCTCTGGCATGAATATTTCATATCT
1201 ATAAAATGACAGATCCCACCAGGAAGGAAGCTGTTGCTTTCTTTGAGGTGATTTTTTTCCTTTGCTCCCTGTTGCTGAAA
1281 CCATACAGCTTCATAAATAATTTTGCTTGCTGAAGGAAGAAAAAGTGTTTTTCATAAACCCATTATCCAGGACTGTTTAT
1361 AGCTGTTGGAAGGACTAGGTCTTCCCTAGCCCCCCCAGTGTGCAAGGGCAGTGAAGACTTGATTGTACAAAATACGTTTT
1441 GTAAATGTTGTGCTGTTAACACTGCAAATAAACTTGGTAGCAAACACTTCCAAAAAAAAAAAAAAAAAA
Target sites Provided by authors  Predicted by miRanda
Experimental Support 1 for Functional miRNA-Target Interaction
miRNA:Target hsa-miR-146a-5p :: BRCA1    [ Functional MTI ]
Validation Method Luciferase reporter assay ,
Conditions MCF-7
Location of target site 3'UTR
Original Description (Extracted from the article) ... Consistent with the target prediction, in a target in vitro assay, we observed that miR-146a could bind to the 3' untranslated regions(UTRs) of BRCA1 and BRCA2 messenger RNAs (mRNAs) and potentially modulate their mRNA expression. ...

- Shen, J. Ambrosone, C. B. DiCioccio, R. A. et al., 2008, Carcinogenesis.

Article - Shen, J. Ambrosone, C. B. DiCioccio, R. A. et al.
- Carcinogenesis, 2008
A G to C polymorphism (rs2910164) is located within the sequence of miR-146a precursor, which leads to a change from a G:U pair to a C:U mismatch in its stem region. The predicted miR-146a target genes include BRCA1 and BRCA2, which are key breast and ovarian cancer genes. To examine whether rs2910164 plays any role in breast and/or ovarian cancer, we studied associations between this polymorphism and age of diagnosis in 42 patients with familial breast cancer and 82 patients with familial ovarian cancer. Breast cancer patients who had at least one miR-146a variant allele were diagnosed at an earlier age than with no variant alleles (median age 45 versus 56, P = 0.029) and ovarian cancer patients who had at least one miR-146a variant allele were diagnosed younger than women without any variant allele (median age 45 versus 50, P = 0.014). In further functional analysis, we found that the variant allele displayed increased production of mature miR-146a from the precursor microRNA compared with the common allele. Consistent with the target prediction, in a target in vitro assay, we observed that miR-146a could bind to the 3' untranslated regions (UTRs) of BRCA1 and BRCA2 messenger RNAs (mRNAs) and potentially modulate their mRNA expression. Intriguingly, the binding capacity between the 3' UTR of BRCA1 and miR-146a was statistically significantly stronger in variant C allele than those in common G allele (P = 0.046). Taken together, our data suggest that breast/ovarian cancer patients with variant C allele miR-146a may have high levels of mature miR-146 and that these variants predispose them to an earlier age of onset of familial breast and ovarian cancers.
LinkOut: [PMID: 18660546]
Experimental Support 2 for Functional miRNA-Target Interaction
miRNA:Target hsa-miR-146a-5p :: BRCA1    [ Functional MTI ]
Validation Method Microarray , qRT-PCR , Western blot , Other
Conditions HMVEC
Location of target site 3'UTR
Tools used in this research miRanda , miRBase Target Database
Original Description (Extracted from the article) ... In summary, we had demonstrated that PMA induced miR- 146a expression in human microvascular endothelial cells and identified that at least 3 genes (CCNA2, PA2G4, and BRCA1) were potentially regulated by miR-146a.// ...

- Hsieh, C. H. Rau, C. S. Jeng, S. F. Lin, C. et al., 2010, Exp Cell Res.

Article - Hsieh, C. H. Rau, C. S. Jeng, S. F. Lin, C. et al.
- Exp Cell Res, 2010
Phorbol 12-myristate 13-acetate (PMA) is known to activate protein kinase C (PKC) and increase angiogenesis in cultured endothelial cells. Using a microRNA (miRNA) array, we found that PMA induced miR-146a expression in human microvascular endothelial cells. The miR-146a expression was dependent on dose and time and independent of PKC activation. Using a combined approach involving predictions using miRanda algorithm and whole genome microarray experiments with or without inhibition of miR-146a expression by LNA-antimir-146a or LNA-control, 29 potential target genes of miR-146a were identified. Because endothelial cell S phase progression is an early event in the induction of angiogenesis, we evaluated 5 cell cycle-related genes from the 29 target genes and found that the transcripts of 3 genes (CCNA2, PA2G4, and BRCA1) were downregulated after PMA treatment, but their expression was rescued upon miR-146a inhibition. However, inhibition of miR-146a expression failed to alter the cell cycle distribution or angiogenesis induced by PMA treatment. By using a combined approach involving computational prediction and a whole genome microarray experiment in the presence or absence of antimir, the observations in this presented article raise the possibility that antimir strategies might be used to identify the potential miRNA targets.
LinkOut: [PMID: 19944095]
MiRNA-Target Expression Profile:

 
MiRNA-Target Interaction Network:
Strong evidence (reporter assay, western blot, qRT-PCR or qPCR)
Other evidence
97 hsa-miR-146a-5p Target Genes:
ID Target Description Validation methods
Strong evidence Less strong evidence
MIRT000006 CXCR4 chemokine (C-X-C motif) receptor 4 5 2
MIRT000301 KIT v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog 1 1
MIRT000303 CFH complement factor H 2 3
MIRT000304 IRAK2 interleukin-1 receptor-associated kinase 2 3 2
MIRT000449 TLR2 toll-like receptor 2 4 1
MIRT000638 FADD Fas (TNFRSF6)-associated via death domain 2 1
MIRT000711 TRAF6 TNF receptor-associated factor 6 5 13
MIRT000712 IRAK1 interleukin-1 receptor-associated kinase 1 5 11
MIRT000945 ROCK1 Rho-associated, coiled-coil containing protein kinase 1 3 1
MIRT001919 BRCA2 breast cancer 2, early onset 2 1
MIRT001920 BRCA1 breast cancer 1, early onset 5 2
MIRT003319 FAF1 Fas (TNFRSF6) associated factor 1 3 1
MIRT004017 CCNA2 cyclin A2 4 2
MIRT004018 PA2G4 proliferation-associated 2G4, 38kDa 4 2
MIRT004249 SNAP25 synaptosomal-associated protein, 25kDa 1 1
MIRT004409 IL8 interleukin 8 3 3
MIRT004459 NFKB1 nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 5 3
MIRT004661 CDKN1A cyclin-dependent kinase inhibitor 1A (p21, Cip1) 2 1
MIRT004730 EGFR epidermal growth factor receptor (erythroblastic leukemia viral (v-erb-b) oncogene homolog, avian) 4 4
MIRT004731 MTA2 metastasis associated 1 family, member 2 3 1
MIRT005463 CD40LG CD40 ligand 4 1
MIRT005581 FAS Fas (TNF receptor superfamily, member 6) 3 1
MIRT005705 CDKN3 cyclin-dependent kinase inhibitor 3 2 1
MIRT005706 KIF22 kinesin family member 22 2 1
MIRT005806 ERBB4 v-erb-a erythroblastic leukemia viral oncogene homolog 4 (avian) 3 1
MIRT006209 SMAD4 SMAD family member 4 4 2
MIRT006530 TLR4 toll-like receptor 4 4 1
MIRT007243 WASF2 WAS protein family, member 2 1 1
MIRT021214 NFIX nuclear factor I/X (CCAAT-binding transcription factor) 1 1
MIRT021215 IRF7 interferon regulatory factor 7 1 1
MIRT021216 RAD54L RAD54-like (S. cerevisiae) 1 1
MIRT021217 PPP1R1C protein phosphatase 1, regulatory (inhibitor) subunit 1C 1 1
MIRT021218 TRIM14 tripartite motif-containing 14 1 1
MIRT021219 TMSB15A thymosin beta 15a 1 1
MIRT021220 ITGB2 integrin, beta 2 (complement component 3 receptor 3 and 4 subunit) 1 1
MIRT021221 SNTG2 syntrophin, gamma 2 1 1
MIRT021222 RSAD2 radical S-adenosyl methionine domain containing 2 1 1
MIRT021223 TIMELESS timeless homolog (Drosophila) 1 1
MIRT021224 PRR15 proline rich 15 1 1
MIRT021225 PEX11G peroxisomal biogenesis factor 11 gamma 1 1
MIRT021226 PLEKHA4 pleckstrin homology domain containing, family A (phosphoinositide binding specific) member 4 1 1
MIRT021227 BGLAP bone gamma-carboxyglutamate (gla) protein 1 1
MIRT021228 SYT12 synaptotagmin XII 1 1
MIRT021229 STAT1 signal transducer and activator of transcription 1, 91kDa 1 1
MIRT021230 LMO2 LIM domain only 2 (rhombotin-like 1) 1 2
MIRT021231 CD83 CD83 molecule 1 1
MIRT021232 IFIT1 interferon-induced protein with tetratricopeptide repeats 1 1 1
MIRT021233 IFITM1 interferon induced transmembrane protein 1 (9-27) 1 1
MIRT021234 OLFML2A olfactomedin-like 2A 1 1
MIRT021235 ISG15 ISG15 ubiquitin-like modifier 1 1
MIRT021236 UHRF1 ubiquitin-like with PHD and ring finger domains 1 1 1
MIRT021237 IFITM3 interferon induced transmembrane protein 3 (1-8U) 1 1
MIRT021238 RGS13 regulator of G-protein signaling 13 1 1
MIRT021239 CCL8 chemokine (C-C motif) ligand 8 1 1
MIRT021240 MTUS2 microtubule associated tumor suppressor candidate 2 1 1
MIRT021241 BLMH bleomycin hydrolase 1 1
MIRT021242 MCPH1 microcephalin 1 1 1
MIRT021243 NMI N-myc (and STAT) interactor 1 1
MIRT021244 HSPA1A heat shock 70kDa protein 1A 1 1
MIRT021245 TRIM22 tripartite motif-containing 22 1 1
MIRT021246 ITGBL1 integrin, beta-like 1 (with EGF-like repeat domains) 1 1
MIRT021247 SPATS2L spermatogenesis associated, serine-rich 2-like 1 1
MIRT021248 POLE2 polymerase (DNA directed), epsilon 2 (p59 subunit) 1 1
MIRT021249 IFI44 interferon-induced protein 44 1 1
MIRT021250 OASL 2'-5'-oligoadenylate synthetase-like 1 1
MIRT021251 LTB lymphotoxin beta (TNF superfamily, member 3) 1 1
MIRT021252 PBLD phenazine biosynthesis-like protein domain containing 1 1
MIRT021253 IFI44L interferon-induced protein 44-like 1 1
MIRT021254 PDIK1L PDLIM1 interacting kinase 1 like 1 1
MIRT021255 MR1 major histocompatibility complex, class I-related 1 1
MIRT021256 IFI27 interferon, alpha-inducible protein 27 1 1
MIRT021257 TBP TATA box binding protein 1 1
MIRT021258 ELL3 elongation factor RNA polymerase II-like 3 1 1
MIRT021259 METTL7A methyltransferase like 7A 1 1
MIRT021260 MCM10 minichromosome maintenance complex component 10 1 1
MIRT021261 LINC00304 chromosome 16 open reading frame 81 1 1
MIRT021262 SDCBP2 syndecan binding protein (syntenin) 2 1 1
MIRT021263 STON2 stonin 2 1 1
MIRT021264 BCL2A1 BCL2-related protein A1 1 1
MIRT021265 COL13A1 collagen, type XIII, alpha 1 1 1
MIRT021266 IRF5 interferon regulatory factor 5 1 1
MIRT021267 MX2 myxovirus (influenza virus) resistance 2 (mouse) 1 1
MIRT021268 VWCE von Willebrand factor C and EGF domains 1 1
MIRT021269 EPSTI1 epithelial stromal interaction 1 (breast) 1 1
MIRT021270 OSBPL1A oxysterol binding protein-like 1A 1 1
MIRT021271 CD86 CD86 molecule 1 1
MIRT021272 IFIT5 interferon-induced protein with tetratricopeptide repeats 5 1 1
MIRT021273 C1orf21 chromosome 1 open reading frame 21 1 1
MIRT021274 GIMAP4 GTPase, IMAP family member 4 1 1
MIRT021275 CCR9 chemokine (C-C motif) receptor 9 1 1
MIRT021276 SAMD9L sterile alpha motif domain containing 9-like 1 1
MIRT021277 IFIT3 interferon-induced protein with tetratricopeptide repeats 3 1 1
MIRT021278 CD80 CD80 molecule 1 1
MIRT021279 SPP1 secreted phosphoprotein 1 1 1
MIRT021280 SLPI secretory leukocyte peptidase inhibitor 2 1
MIRT035533 L1CAM L1 cell adhesion molecule 1 1
MIRT045694 MSC musculin 1 1