Accession ID: MIRT001920 [miRNA, hsa-miR-146a :: BRCA1, target gene]
|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|
|Mature Sequence||57| CCUCUGAAAUUCAGUUCUUCAG |78|
|Putative hsa-miR-146a-3p Targets|
|Mature Sequence||21| UGAGAACUGAAUUCCAUGGGUU |42|
|Putative hsa-miR-146a-5p Targets|
|Synonyms||BRCAI, BRCC1, BROVCA1, IRIS, PNCA4, PSCP, RNF53|
|Description||breast cancer 1, early onset|
|Other Transcripts||NM_007297, NM_007298, NM_007294, NM_007300|
hsa04120 Ubiquitin mediated proteolysis - Homo sapiens (human)
|Putative miRNA Targets on BRCA1|
|3'UTR of BRCA1
(miRNA target sites are highlighted)
>BRCA1|NM_007299|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
|miRNA-target interactions (Predicted by miRanda)||
|miRNA:Target||hsa-miR-146a :: BRCA1 [ Functional MTI ]|
|Validation Method||Luciferase reporter assay|
|Location of target site||3'UTR, unknown|
|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.
- 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]
|miRNA:Target||hsa-miR-146a :: BRCA1 [ Functional MTI ]|
|Validation Method||Microarray , qRT-PCR , Western blot|
|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.
Identification of the potential target genes of microRNA-146a induced by PMA treatment in human microvascular endothelial cells- 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]