Accession ID: MIRT004496 [miRNA, hsa-miR-145 ::
FLI1, target gene]
| pre-miRNA ID | hsa-mir-145 LinkOut: [miRBase ] |
|---|---|
| Synonyms | MIRN145, miR-145, miRNA145, MIR145 |
| Description | Homo sapiens miR-145 stem-loop |
| Comment | This miRNA sequence was predicted based on homology to a verified miRNA from mouse . |
| 2nd Structure of pre-miRNA |  |
| Mature miRNA | hsa-miR-145-3p |
|---|---|
| Mature Sequence | 54| GGAUUCCUGGAAAUACUGUUCU |75 |
| Evidence | Experimental |
| Experiments | Cloned |
| Putative hsa-miR-145-3p Targets | LinkOut: [ TargetScanS 5.1 | MicroCosm | microRNA.org | miRecords | miRDB | miRo | miRNAMap 2.0 ] |
| Mature miRNA | hsa-miR-145-5p |
| Mature Sequence | 16| GUCCAGUUUUCCCAGGAAUCCCU |38 |
| Evidence | Experimental |
| Experiments | Cloned |
| Putative hsa-miR-145-5p Targets | LinkOut: [ TargetScanS 5.1 | MicroCosm | microRNA.org | miRecords | miRDB | miRo | miRNAMap 2.0 ] |
 |
| Gene Symbol | FLI1 LinkOut: [ Entrez Gene | BioGPS | Wikipedia | iHop ] | ||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Synonyms | EWSR2, SIC-1 | ||||||||||||||||||||
| Description | Friend leukemia virus integration 1 | ||||||||||||||||||||
| Transcript | NM_001167681 LinkOut: [ RefSeq ] | ||||||||||||||||||||
| Other Transcripts | NM_002017 | ||||||||||||||||||||
| Expression | LinkOut: [ BioGPS ] | ||||||||||||||||||||
| Putative miRNA Targets on FLI1 | LinkOut: [ TargetScan 5.1 | MicroCosm | miRNAMap 2.0 ] | ||||||||||||||||||||
| 3'UTR of FLI1 (miRNA target sites are highlighted) |
>FLI1|NM_001167681|3'UTR 1 TAGAAGCTTACTCATCAGTGGCCTTCTAGCTGAAGCCCATCCTGCACACTTACTGGATGCTTTGGACTCAACAGGACATA 81 TGTGGCCTTGAAGGGAAGACAAAACTGGATGTTCTTTCTTGTTGGATAGAACCTTTGTATTTGTTCTTTAAAAACATTTT 161 TTTTAATGTTGGTAACTTTTGCTTCCTCTACCTGAACAAAGAGATGAATAATTCCATGGGCCAGTATGCCAGTTTGAATT 241 CTCAGTCTCCTAGCATCTTGTGAGTTGCATATTAAGATTACTGGAATGGTTAAGTCATGGTTCTGAGAAAGAAGCTGTAC 321 GTTTTCTTTATGTTTTTATGACCAAAGCAGTTTCTTGTCAATACACGGGGTTCAGTATGACACAGAATCATGGACTTAAC 401 CCGTCATGTTCTGGTTTGAGATTTAGTGACAAATAGAGGTGGGAAGCTTATAATCTAATTTTAGGAGGACCAAATTCAGT 481 GGATGGCAACTGGAACATTGATTGTAAGGCCAGTGAAGTTTTCACCCAACTGGAATTTGATGGAAAGAAGGTTTGTGTGT 561 TTAAGACGCCAAGGGCATTGCAGAATCCCTCTCAGTGGACAGTATGCACTCAGCTGACCACTCTCTCTAGAAATAGTCAA 641 GATATGAACTAAGAAATTTTAATGCAAATACATACATTCCTGAAAGACGGGGAATTAAATTACTAATTTTTTTTTTTTTT 721 TAAATGATGACAGTGGTCCCAGAACTTGGAAAAGTTGTAGGGATTTCTAAACTCAAGCAGATTCGCAAGTGCTGTGCGCT 801 TGTCAGACCATCAGACCAGGGCCAACCAATCAGAAGGCAACTTACTGTATAAATTATGCAGAGTTATTTTCCTATATCTC 881 ACAGTATTAAAAATAAATAATTAAAAATTAAGAATAAATAAACGAGTTGACCTCGGTCACAAAAGCAGTTTTACTATCGA 961 ATCAATCGCTGTTATTTTTTTTAATGTAATTTGTACATCTTTTTTCAATCTGTACATTTGGGCTGTCTGTATGTTTTTAT 1041 AGCTGGTTTTTAAAAAGCATAATATGCCTATAGCTGAAAAGGAAACAGGGCTGTTTAAGTCACTGACTTATGAGAAAGCA 1121 AAGCACTGGTACAGTTATTTAACAGGCATACACAAGCAGGGAAAAGATAATCCATTTAGATCTTTAATGCTTTGGAAATG 1201 CGTGTAACAGTACTGCAATAATCACAGCTCTGGGAAAAACAACGAAACTTTCCCTTGTGGAGAGGAGGGATTTTCCTGCT 1281 CTATATAAGCAACATATTTTTAGACATTAAAATATATATAATTTTGCAGGTAATTGTTGACTTTTTTAACTATATTAAGT 1361 GTTAAGCTGACAACTGTCAAAGAAGACCATGTTGTAAAATAATTTGACTAAATAAATGGTTCCTTCTCTCAGTGCTGAGG 1441 ACAGTTTTCTTATTTACCGCCCCCGTTAGGTCAAAGGGTTTTCCCTGGGGAACTTTCCTATTTACTTCTTGCACTATCAA 1521 GAATTTTTCGAATGTACCTACTGCAGTACAGCAGAAGGTAAAAAATCAGTGTGGTTTTTCATTGTTGTTGATGATGTTTG 1601 TAGTGTTTTTGTGTGTGTTATTTAAATCTTCCTCCAGCCTAAAAGGGTTTTATAAAACAGCAGCTAAGGCCATGGATAAA 1681 CCTGTATGTAAGGACTGGAGCAAAGCGAGCTGGTCTATCCAGACTGGTCTGTGAGATTTAACTCTGCAGCCTCCCCTGGG 1761 CACTTCAGACCCAGACGGCCACCTTCTGCCACTCCAGCAAAGAATAAGCGCCCTGCTTCCTTCAGGTCTCAGACCAGGAC 1841 TTTATGGCTCATGCAGATTTTTAAGGTCATTTTTCTTCCCAAGGAAGAAACTTGCCTCCAGTTCCTTCACTGTTAGGTAG 1921 CTTATTTTCATTTTCTCTATTTTACAATGAAAAGAGTGAGACCTGGGAAGTCCTTGATTTGCAAGGAATTAGACTCACAG 2001 CATTGGTAACCCTAGAACCTTCTTAGGGTAACACTAAGTACCTTCTAGACAACATGTCTACCTAAATGAAATGGGATGTG 2081 TTTCGGAACATTTGTCTCCAGTTTTTTTTTAATCTTGCACCCTGCCATTTAAAAAGATGTGTAAAGCACATATTCTCAAC 2161 ATATGCACATTGATTTATAAATCATATATACAAACTGTTACATTATTCTTCATATTAGAAAACAAATACAAAATAGAACA 2241 TTTTAAATGGTGATATAAAAATAAATTGAAACTGAAATTCTAAAAAAAAAAAAAAA Target sites Provided by authors Predicted by miRanda |
||||||||||||||||||||
| miRNA-target interactions (Predicted by miRanda) |
|
| miRNA:Target | hsa-miR-145 :: FLI1 [ Functional MTI ] |
|---|---|
| Validation Method | qRT-PCR , Luciferase reporter assay , Western blot |
| Conditions | HEK293T, A673 |
| Location of target site | 3'UTR |
| Tools used in this research | TargetScan |
| Original Description (Extracted from the article) | ... (F, left panels) miRNA145 specifically represses its target gene, FLI-1, in a luciferase assay performed in HEK-293 cells engineered to express a luciferase reporter vector containing the human wild-type FLI-1 3'UTR.//Among genes found to be modulated by miRNA145 in ESFT cells, SOX2, a core reprogramming factor and EWS-FLI-1 target gene, was induced more than a thousand-fold during the emergence of a NCSC phenotype in hpMSCEWS-FLI-1s. ... - Riggi, N. Suva, M. L. De Vito, C. Provero, et al., 2010, Genes Dev. |
| Article |
- Riggi, N.
Suva, M. L.
De Vito, C.
Provero, et al. - Genes Dev, 2010
Cancer stem cells (CSCs) display plasticity and self-renewal properties reminiscent of normal tissue stem cells, but the events responsible for their emergence remain obscure. We recently identified CSCs in Ewing sarcoma family tumors (ESFTs) and showed that they retain mesenchymal stem cell (MSC) plasticity. In the present study, we addressed the mechanisms that underlie ESFT CSC development. We show that the EWS-FLI-1 fusion gene, associated with 85%-90% of ESFTs and believed to initiate their pathogenesis, induces expression of the embryonic stem cell (ESC) genes OCT4, SOX2, and NANOG in human pediatric MSCs (hpMSCs) but not in their adult counterparts. Moreover, under appropriate culture conditions, hpMSCs expressing EWS-FLI-1 generate a cell subpopulation displaying ESFT CSC features in vitro. We further demonstrate that induction of the ESFT CSC phenotype is the result of the combined effect of EWS-FLI-1 on its target gene expression and repression of microRNA-145 (miRNA145) promoter activity. Finally, we provide evidence that EWS-FLI-1 and miRNA-145 function in a mutually repressive feedback loop and identify their common target gene, SOX2, in addition to miRNA145 itself, as key players in ESFT cell differentiation and tumorigenicity. Our observations provide insight for the first time into the mechanisms whereby a single oncogene can reprogram primary cells to display a CSC phenotype.
LinkOut: [PMID: 20382729]
|
| miRNA:Target | hsa-miR-145 :: FLI1 [ Functional MTI ] | ||||||
|---|---|---|---|---|---|---|---|
| Validation Method | Luciferase reporter assay , Northern blot , qRT-PCR , Western blot | ||||||
| Conditions | SW620, HCT116, 293T | ||||||
| Location of target site | 3'UTR | ||||||
| Tools used in this research | miRanda, PicTar, TargetScan | ||||||
| Original Description (Extracted from the article) | ... The authors demonstrated that miR-145 targets a putative microRNA regulatory element in the 3'- untranslated region (UTR) of FLI1// ... - Zhang, J. Guo, H. Zhang, H. Wang, H. Qian, et al., 2011, Cancer. |
||||||
| miRNA-target interactions (Provided by authors) |
|
||||||
| Article |
- Zhang, J.
Guo, H.
Zhang, H.
Wang, H.
Qian, et al. - Cancer, 2011
BACKGROUND: Tumor suppressor microRNA miR-145 is commonly down-regulated in colon carcinoma tissues, but its specific role in tumors remains unknown. METHODS: In this study, the authors identified the Friend leukemia virus integration 1 gene (FLI1) as a novel target of miR-145. FLI1 is involved in t(11;22)(q24:q12) reciprocal chromosomal translocation in Ewing sarcoma, and its expression appears to be associated with biologically more aggressive tumors. RESULTS: The authors demonstrated that miR-145 targets a putative microRNA regulatory element in the 3'-untranslated region (UTR) of FLI1, and its abundance is reversely associated with FLI1 expression in colon cancer tissues and cell lines. By using a luciferase/FLI1 3'-UTR reporter system, they found that miR-145 down-regulated the reporter activity, and this down-regulation was reversed by anti-miR-145. Mutation of the miR-145 microRNA regulatory element sequence in the FLI1 3'-UTR abolished the activity of miR-145. miR-145 decreased FLI1 protein but not FLI1 mRNA, suggesting a mechanism of translational regulation. Furthermore, the authors demonstrated that miR-145 inhibited cell proliferation and sensitized LS174T cells to 5-fluorouracil-induced apoptosis. CONCLUSIONS: Taken together, these results suggest that miR-145 functions as a tumor suppressor by down-regulating oncogenic FLI1 in colon cancer. Cancer 2011. (c) 2010 American Cancer Society.
LinkOut: [PMID: 20737575]
|
| miRNA:Target | hsa-miR-145 :: FLI1 [ Functional MTI ] |
|---|---|
| Validation Method | Luciferase reporter assay , Western blot |
| Conditions | TC252 |
| Location of target site | 3'UTR |
| Tools used in this research | TargetScan |
| Original Description (Extracted from the article) | ... Co-transfection of the anti-mir-145 oligo- nucleotide with pri-mir-145 or with the mature mir-145 fully rescued luciferase activity, confirming the specifi- city of the suppressive pri-mir-145 effect on the FLI1 3'-untranslated region. ... - Ban, J. Jug, G. Mestdagh, P. Schwentner, R. et al., 2011, Oncogene. |
| Article |
- Ban, J.
Jug, G.
Mestdagh, P.
Schwentner, R. et al. - Oncogene, 2011
EWS-FLI1 is a chromosome translocation-derived chimeric transcription factor that has a central and rate-limiting role in the pathogenesis of Ewing's sarcoma. Although the EWS-FLI1 transcriptomic signature has been extensively characterized on the mRNA level, information on its impact on non-coding RNA expression is lacking. We have performed a genome-wide analysis of microRNAs affected by RNAi-mediated silencing of EWS-FLI1 in Ewing's sarcoma cell lines, and differentially expressed between primary Ewing's sarcoma and mesenchymal progenitor cells. Here, we report on the identification of hsa-mir-145 as the top EWS-FLI1-repressed microRNA. Upon knockdown of EWS-FLI1, hsa-mir-145 expression dramatically increases in all Ewing's sarcoma cell lines tested. Vice versa, ectopic expression of the microRNA in Ewing's sarcoma cell lines strongly reduced EWS-FLI1 protein, whereas transfection of an anti-mir to hsa-mir-145 increased the EWS-FLI1 levels. Reporter gene assays revealed that this modulation of EWS-FLI1 protein was mediated by the microRNA targeting the FLI1 3'-untranslated region. Mutual regulations of EWS-FLI1 and hsa-mir-145 were mirrored by an inverse correlation between their expression levels in four of the Ewing's sarcoma cell lines tested. Consistent with the role of EWS-FLI1 in Ewing's sarcoma growth regulation, forced hsa-mir-145 expression halted Ewing's sarcoma cell line growth. These results identify feedback regulation between EWS-FLI1 and hsa-mir-145 as an important component of the EWS-FLI1-mediated Ewing's sarcomagenesis that may open a new avenue to future microRNA-mediated therapy of this devastating malignant disease.Oncogene advance online publication, 10 January 2011; doi:10.1038/onc.2010.581.
LinkOut: [PMID: 21217773]
|