Accession ID: MIRT000665 [miRNA, hsa-miR-206 :: NOTCH3, target gene]
|Description||Homo sapiens miR-206 stem-loop|
|Comment||This miRNA sequence is predicted based on homology to a verified miRNA from mouse .|
|2nd Structure of pre-miRNA|
|Mature Sequence||53| UGGAAUGUAAGGAAGUGUGUGG |74|
|Putative hsa-miR-206 Targets|
|Description||Notch homolog 3 (Drosophila)|
hsa04320 Dorso-ventral axis formation - Homo sapiens (human)
hsa04330 Notch signaling pathway - Homo sapiens (human)
|Putative miRNA Targets on NOTCH3|
|3'UTR of NOTCH3
(miRNA target sites are highlighted)
>NOTCH3|NM_000435|3'UTR 1 TGAGACGCTCGTCAGTTCTTAGATCTTGGGGGCCTAAAGAGACCCCCGTCCTGCCTCCTTTCTTTCTCTGTCTCTTCCTT 81 CCTTTTAGTCTTTTTCATCCTCTTCTCTTTCCACCAACCCTCCTGCATCCTTGCCTTGCAGCGTGACCGAGATAGGTCAT 161 CAGCCCAGGGCTTCAGTCTTCCTTTATTTATAATGGGTGGGGGCTACCACCCACCCTCTCAGTCTTGTGAAGAGTCTGGG 241 ACCTCCTTCTTCCCCACTTCTCTCTTCCCTCATTCCTTTCTCTCTCCTTCTGGCCTCTCATTTCCTTACACTCTGACATG 321 AATGAATTATTATTATTTTTATTTTTCTTTTTTTTTTTACATTTTGTATAGAAACAAATTCATTTAAACAAACTTATTAT 401 TATTATTTTTTACAAAATATATATATGGAGATGCTCCCTCCCCCTGTGAACCCCCCAGTGCCCCCGTGGGGCTGAGTCTG 481 TGGGCCCATTCGGCCAAGCTGGATTCTGTGTACCTAGTACACAGGCATGACTGGGATCCCGTGTACCGAGTACACGACCC 561 AGGTATGTACCAAGTAGGCACCCTTGGGCGCACCCACTGGGGCCAGGGGTCGGGGGAGTGTTGGGAGCCTCCTCCCCACC 641 CCACCTCCCTCACTTCACTGCATTCCAGATGGGACATGTTCCATAGCCTTGCTGGGGAAGGGCCCACTGCCAACTCCCTC 721 TGCCCCAGCCCCACCCTTGGCCATCTCCCTTTGGGAACTAGGGGGCTGCTGGTGGGAAATGGGAGCCAGGGCAGATGTAT 801 GCATTCCTTTGTGTCCCTGTAAATGTGGGACTACAAGAAGAGGAGCTGCCTGAGTGGTACTTTCTCTTCCTGGTAATCCT 881 CTGGCCCAGCCTCATGGCAGAATAGAGGTATTTTTAGGCTATTTTTGTAATATGGCTTCTGGTCAAAATCCCTGTGTAGC 961 TGAATTCCCAAGCCCTGCATTGTACAGCCCCCCACTCCCCTCACCACCTAATAAAGGAATAGTTAACACTCAAAAAAAAA 1041 AAAAAAAAAA
|miRNA-target interactions (Predicted by miRanda)||
|miRNA:Target||hsa-miR-206 :: NOTCH3 [ Functional MTI ]|
|Validation Method||Luciferase reporter assay , qRT-PCR , Western blot|
|Location of target site||3'UTR|
|Tools used in this research||miRanda, PicTar, TargetScan|
|Original Description (Extracted from the article)||... miR-206 targets and regulates human notch3.//As expected, miR-206 showed a strong inhibitory effect on normal (Fig. 2A, left) but not deleted (Fig. 2A, right) or mutated (supplemental Fig. S2B) human notch3 3'-UTR-luciferase activity. Similarly, forced expression of full-length notch3 largely rescued the repressive effect of miR-206 on human notch3 3'-UTR-lucif- erase activity (Fig. 2A, left). When the cells were treated with a specific inhibitor of miR-206, the repression of the human notch3 3'-UTR by miR-206 was moderately released (Fig. 2B, left), suggesting that a higher dose of the miR-206 inhibitor would be required to efficiently block the inhibitory effect of miR-206 on the activity of the human notch3 3'-UTR.//As expected, ectopic expression of miR-206 resulted in a significant reduction of human Notch3 protein expression (Fig. 2C and supplemental Fig. S3A). In addition, the level of human notch3 mRNA was also repressed by miR-206 (Fig. 2D) ...
- Song, G. Zhang, Y. Wang, L., 2009, J Biol Chem.
|miRNA-target interactions (Provided by authors)||
MicroRNA-206 targets notch3, activates apoptosis, and inhibits tumor cell migration and focus formation- Song, G. Zhang, Y. Wang, L.
- J Biol Chem, 2009
MicroRNAs contribute to cancer development by acting as oncogenes or tumor suppressor genes. However, only a few microRNA target genes were determined. We identified a nearly perfect complementarity between miR-206 and the 3'-untranslated regions of both mouse and human notch3. Expression of miR-206 decreased the luciferase activity dose-dependently when cotransfected with the mouse or human notch3 3'-untranslated region-luciferase reporter containing the miR-206 target site in HeLa cells. This suppression was relieved by deletion and mutation of the miR-206-binding site and was partially recovered by expression of notch3 or by a specific inhibitor of miR-206. Interestingly, overexpression of miR-206 decreased the levels of both Notch3 protein and mRNA. Expression of miR-206 markedly induced apoptotic cell death and blocked the anti-apoptotic activity of Notch3. In addition, ectopic expression of miR-206 inhibited HeLa cell migration and focus formation. Therefore, we identified miR-206 as a pro-apoptotic activator of cell death, which was associated with its inhibition of notch3 signaling and tumor formation. The inhibition of cancer cell migration and focus formation by miR-206 strongly suggests that miR-206 may function as a novel tumor suppressor.LinkOut: [PMID: 19723635]