pre-miRNA Information | |
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pre-miRNA | hsa-mir-6737 |
Genomic Coordinates | chr1: 153962351 - 153962420 |
Description | Homo sapiens miR-6737 stem-loop |
Comment | None |
RNA Secondary Structure | ![]() |
Mature miRNA Information | ||||||||||||||||||||||
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Mature miRNA | hsa-miR-6737-5p | |||||||||||||||||||||
Sequence | 6| UUGGGGUGGUCGGCCCUGGAG |26 | |||||||||||||||||||||
Evidence | Experimental | |||||||||||||||||||||
Experiments | Meta-analysis | |||||||||||||||||||||
SNPs in miRNA |
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Putative Targets |
Gene Information | |||||||||||||||||||||
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Gene Symbol | PLCG2 | ||||||||||||||||||||
Synonyms | APLAID, FCAS3, PLC-IV, PLC-gamma-2 | ||||||||||||||||||||
Description | phospholipase C gamma 2 | ||||||||||||||||||||
Transcript | NM_002661 | ||||||||||||||||||||
Expression | |||||||||||||||||||||
Putative miRNA Targets on PLCG2 | |||||||||||||||||||||
3'UTR of PLCG2 (miRNA target sites are highlighted) |
>PLCG2|NM_002661|3'UTR 1 AAGCTGGGGTATGTGTGTAAGGGTATTGTGTGTGTGCGCATGTGTGTTTGCATGTAGGAGAACGTGCCCTATTCACACTC 81 TGGGAAGACGCTAATCTGTGACATCTTTTCTTCAAGCCTGCCATCAAGGACATTTCTTAAGACCCAACTGGCATGAGTTG 161 GGGTAATTTCCTATTATTTTCATCTTGGACAACTTTCTTAACTTATATTCTTTATAGAGGATTCCCCAAAATGTGCTCCT 241 CATTTTTGGCCTCTCATGTTCCAAACCTCATTGAATAAAAGCAATGAAAACCTTGATCAATTAAGCCTTCTGTTGCACGA 321 CCTGTGCAGTGAACAGGATTTCTTTTCTGGCCAAGAAGATTCTACCTCTAATGATCCAGGTAACTGATGTCCATGGAGGA 401 TGAGCTGGAAATGTAAGAAACTATTCATGAGATTCTGAAAAGGATTTTAACTCAAAGGCAAATGATTCCATAAGGGCCCA 481 AAGAGAAGCCCTACCCACAGGCAGCCTGCTCAGTTCAATGTACTTTAACTACCACCGGCTGCCTGCTGCAGTCCACAAGA 561 AAATGGCTGAGTGATGGGATCTGTTCATTAAGACAATTTCTAATTAATGGTGACAGCTTGTTTTGTGACTAGAGTTACTG 641 GGATGGAGGGTAGGAATCTTGGGGCCTCTTTGTTTTAAAAAGCCCATCAGAGAGACCAGAGCCGTGCTGCAGGGGCAGGT 721 TCTCACTTGCCCCTGGCTCTGCCAGCTGCTGGGAGGCTCTGGCCCCACTAGTCCCTCATGGCCCTACTGAACTGGCTGGG 801 AGGCTGCTGGAATGGCCCTTGGTCCACAGCTCTCCACAGGCAAGAGGTCAACTGCTGCTTGAAAGAGGTAGACAAAAGTT 881 AGGTTGATGGCGAAATGTCTCTGGGTTACCCAGTCTTCTGGAGCAGCAAGCTGAGCTTTAATGGGCTAAGCATTAGGGTG 961 TTACAGAAAATTTCAAATGCAGCCATCTCCCTTGGGGCAGATCTACCTAGTTCATGACAGTATGTGCGGCTGGCCAGGGC 1041 TTTACACCTCTGCATCTTAAGTTGTTAATACATACCAATAATGTAATATGGCTTTTTAAAGGAGAGGAGAGTGCTGGGTT 1121 GGGAAGGGAGGTGGTTGGTAGAGTCACAACTTCTCAATGAGTGAATTTACAGCTGATGGGAAAAGGAGTGTAACTGTGAA 1201 AAACGATGGCTGTGGTGGGGAAGAACAAACCAGCAGTAAGCCTGATGTTTGATGTGGATGGAACTGGCCCCTAGAAACCC 1281 ATCTGACCCTCCTCTTGTTACCCGAAATGCTGGGCTTAGTATGCATGTACTGCTGAAAAGCAGGGCAGAACAAATCAGGC 1361 TCTGACCAGAAGATCCTTCTGGTCCCTTCACTCTACAAAAACTTACTGATCACCTCCACATGCCAAATACAGTGCCAAGA 1441 TTTGGGGGTGTGGATGTTTAAACAAAAAGCTGTGGGTCTCATCAATCATCTCCATCCACAAGCTCCTAAAAGAAAGCCAT 1521 TTACCTCGCTTGAAGCCAGGAACACAGGGAACAGCAGTCTGGCCAAGGAAGGGCTGTTATCTGGTGCTATCACTCCAGTT 1601 ACTCCTCCAACTGGGAGCTGCTATTTTATTTGGCAGTCAGCAACTGAAGAAAGAACATTCCTCTTAGTGGCAGATGTTCA 1681 AAGCAACTTTCAAGAAAGGCTAGGTGAGAAAGGCACTGGGATGAGTGCTGCAGGCACTCTGTAGCCAGGGCCCCATTAGC 1761 CTTTGGCCAGGTAGCCACCAGAACCTATTTATTGCACCTGGCATCTCCCCCAACCCCTCTCAGCTCTGTTAGGACTTCCA 1841 CACAGCAGAGCTCAGGTGTTGCTGTCATTACCTCCTTTCAGCTCCTCACTTCATTCTACTTTAAAGCCACAGTGCTAAGG 1921 CCTGCATCCCCTTTCTGCCCAAATGGGTTTTTTGCTACCATATCAAAGAACCTGACATATGGCGGCATAGGAAGCAGAAG 2001 CTAAGCCTCTCTCCAGCTGCTGCTGTGTAAAATCCATGCGTGGCCAAAGAGAAGTCAGGGGATTATGACATAAATGGTGC 2081 TGGGAAGAACCCTCTGCCTAAAACTGTCTCCTTCTCCTGGTGCTACAACCGGAATCCACCATGAGAGAGTACTTTCTTCG 2161 GTTCTTTCCTCCTGTCCTTGACAGAGTAACACGTTAATCTGGTTCTTGGTGGTGTTAGGGACTGATTCTCTCAGGAAAGG 2241 CACACATGGTATGATGGCTCTTCCCAGAGTCTATGTGATGCTACATAACTTCAGTATCTAGCTGAGACATGCTTCCTACA 2321 TGACTGTTAAAGCACAGCCAATCCAGGCCAAGAAGACTAGTAACAGGCACATTCTGAAAGATGGAAGCAGCACTGATAGA 2401 TCAAAACCACCACTGCATATGTATTACACTGTTTTTGTTCACCATTTTCCTAAGTGTGTTATTTAGAATATTGGTTATTA 2481 CAAGGAAAAATAAAGTGGGGAGGCTGGTTAGGCCTTGTGAGTTTGGGAAACTTAGGTTATAAAAACTAAATAAAGTTTTT 2561 CTACTGTGAGACTAGATGTGCAGGAGTGAAAGGTGTAGAGGGTCTTGTTTTCCAAATTCGATCTCAGAATCTTTTTGCCA 2641 GAAGTGTCTCATGGGACTTATCTATAGTGGAACACATTTGAAGACCTACTGCTCTATTAAGAAGGCAGCCGGACAACATG 2721 TTCTAATACTTCGTATGCTTTGTGACCTAGTTAAAATCTAAACTTAAGTCGCCATGGCCAGTGGCCTTTAGATTAAGCTA 2801 GCCTTACCCCTGGGAGTATACCAGAGCTTTCCAAGGAATACACAGACTCCAGTACTCTCAGGGGAGCAGTGTTCAGAGCC 2881 TCATCTTCCTGTTATATTCTTCTCTAAGATTCATCTGCCTGAGAAAATGCCCTTTTCTCACCTTACAAAAGAAAATATGG 2961 CTGTCTCCACCTCTAGTCTTACTGTAGAGCATGTCCCAAGGTGTAAAAATTCAAAATGTGGATATTTGGAAAGTGAAAGA 3041 CTTATCAACAGGGCACAAATCTTTTTGCAAATGGATTTTCCAAGTTTTTCTGGTGGTTCCAAATTTTTTGCTTTCAACAA 3121 AGTGGGAGGAACAGCCTGTAGATTTCTGAGTCTCTTAGCATGTAACTACAAAGGGGTTGGAAGAATTCAGTGATTCTGCT 3201 ATCATAAAGCTTCCGTTCCCATTGATGTATCTGTGTGAACAAGGATCAACATCTCCATAAATGAAATTGAAAACGGAAAA 3281 TAGAATTGATGATGAACTTTGGCTCAATCTTAAGATGTTATCAATCTACATAGATGAAATAATTGTGGAGAAAAGCCCTC 3361 TTTATCTCATTAAGTGATACATTTCCAAAGAAGTTTTACTATGTTTAATAATTTAGTGAAATTTGGGCTATGTGTTTATT 3441 GATTCAGCTCAATCCAGAGGAAAATTTTAAAGGCTTACAGCCTTAGGATTATAGGATACTATATAATACTTTTGGTACAG 3521 AGATAGAATTAAATAACATAAAAATCAAAAATTTATTAGGCTAAAATTTTGAGGGAGAAGTGGTATGAAAATACAAATTC 3601 AAGGAGTAAAAGGAAAAGTGGGGCATTCCTTGCTACTAAAAATTGCCTTGTTCCAGGTAAGACTGATCATAAAAAAATGG 3681 CCCTGTTCATAAAATTTTTAAAAAGATCATAGTATCTATCAAATAACTTATATTAAGAACCTCCTGGGCTAAATTTAAAA 3761 AGTAATACAACAGTTTTATTTAAACATGTAGTGTCTACGGTATGCCAGCACTTTGCAGCTATTTATAATGAGAAATTTTA 3841 GATGTCAATATAGCAATGTGCAAGAAGATAGAGATTTTCAAAATTCACTTAAGAGTATCTGAGCATAAAATGTTAAGATT 3921 GCTGATCGGATGTGAGGGCGATCTGGCTGCGACATCTGTCACCCCATTGATCGCCAGGGTTGATTCGGCTGATCTGGCTG 4001 GCTAGGTGGGTGTCCCCTTCCTACCTCACCGCTCCATGTGCGTCCCTCCCGAAGCTGCGCGCTCCGTCGAAGAGGACGAC 4081 CAACCCCGATAGAGGAGGACCGGTCTTCGGTCAAGGGTATACGAGTAGCTGCGCTCCCCTGCTGGAACCTCCAAACAAGC 4161 TCTCAAGATTGCTGATCTAGGGCCACTAAGTGATGAATTGTATTTGGAAGCAAAAAGGATGGCTAAAAAGGACCTCAACC 4241 CTTTTGACTTTAAAAGGAAAATAGCTTAACCTTCAACCTGTGTGACATTTAACTTTTTGAACCCAACCGTAAAAGCTATC 4321 TTCTAACCAACAAAAAGTTAATAATTAGATTTGGAATTATACAGAATTAGAAAATTGGCATTTAAAAATACTCAATAATT 4401 TGTCCCTGGTTTTTAATTTTCAAAATATTTTCTTTTTGAAGAGCCAGATTCCAGTGATCCTGCCTCTCAGAAATTTCCAC 4481 ATTTCTTATTTTTCATTAGGCCTTAAGAAGCTGCATTTGTAAACTTGTGTTTCATTATTAAAGCTTAATTTATTTTTTAT 4561 ATAAATAGTATGTGCTTTGTGTACATAGAGAATTAAGTGAATGAGTCACACAGATGTTGGCTGTTGTTAATGTGAAAATT 4641 AAACAGCTGTATCACATTTTGAAAAATAAAAGTTTCATCTGAATGAATATAGCAA Target sites
Provided by authors
Predicted by miRanda
DRVs
SNPs
DRVs & SNPs
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miRNA-target interactions (Predicted by miRanda) |
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DRVs in gene 3'UTRs | |||||||||||||||||||||
SNPs in gene 3'UTRs |
Experimental Support 1 for Functional miRNA-Target Interaction | |
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miRNA:Target | ---- |
Validation Method |
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Conditions | HEK293 |
Location of target site | 3'UTR |
Tools used in this research | TargetScan , miRTarCLIP , Piranha |
Original Description (Extracted from the article) |
...
PAR-CLIP data was present in GSM545215. RNA binding protein: AGO4. Condition:Control
... - Hafner M; Landthaler M; Burger L; Khorshid et al., 2010, Cell. |
Article |
- Hafner M; Landthaler M; Burger L; Khorshid et al. - Cell, 2010
RNA transcripts are subject to posttranscriptional gene regulation involving hundreds of RNA-binding proteins (RBPs) and microRNA-containing ribonucleoprotein complexes (miRNPs) expressed in a cell-type dependent fashion. We developed a cell-based crosslinking approach to determine at high resolution and transcriptome-wide the binding sites of cellular RBPs and miRNPs. The crosslinked sites are revealed by thymidine to cytidine transitions in the cDNAs prepared from immunopurified RNPs of 4-thiouridine-treated cells. We determined the binding sites and regulatory consequences for several intensely studied RBPs and miRNPs, including PUM2, QKI, IGF2BP1-3, AGO/EIF2C1-4 and TNRC6A-C. Our study revealed that these factors bind thousands of sites containing defined sequence motifs and have distinct preferences for exonic versus intronic or coding versus untranslated transcript regions. The precise mapping of binding sites across the transcriptome will be critical to the interpretation of the rapidly emerging data on genetic variation between individuals and how these variations contribute to complex genetic diseases.
LinkOut: [PMID: 20371350]
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Experimental Support 2 for Functional miRNA-Target Interaction | |
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miRNA:Target | ---- |
Validation Method |
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Conditions | hESCs (WA-09) |
Disease | 5336.0 |
Location of target site | 3'UTR |
Tools used in this research | TargetScan , miRTarCLIP , Piranha |
Original Description (Extracted from the article) |
...
"PAR-CLIP data was present in SRR359787. RNA binding protein: AGO2. Condition:4-thiouridine
... - Lipchina I; Elkabetz Y; Hafner M; Sheridan et al., 2011, Genes & development. |
Article |
- Lipchina I; Elkabetz Y; Hafner M; Sheridan et al. - Genes & development, 2011
MicroRNAs are important regulators in many cellular processes, including stem cell self-renewal. Recent studies demonstrated their function as pluripotency factors with the capacity for somatic cell reprogramming. However, their role in human embryonic stem (ES) cells (hESCs) remains poorly understood, partially due to the lack of genome-wide strategies to identify their targets. Here, we performed comprehensive microRNA profiling in hESCs and in purified neural and mesenchymal derivatives. Using a combination of AGO cross-linking and microRNA perturbation experiments, together with computational prediction, we identified the targets of the miR-302/367 cluster, the most abundant microRNAs in hESCs. Functional studies identified novel roles of miR-302/367 in maintaining pluripotency and regulating hESC differentiation. We show that in addition to its role in TGF-beta signaling, miR-302/367 promotes bone morphogenetic protein (BMP) signaling by targeting BMP inhibitors TOB2, DAZAP2, and SLAIN1. This study broadens our understanding of microRNA function in hESCs and is a valuable resource for future studies in this area.
LinkOut: [PMID: 22012620]
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Experimental Support 3 for Functional miRNA-Target Interaction | |||||||
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miRNA:Target | ---- | ||||||
Validation Method |
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Conditions | HEK293 | ||||||
Disease | 5336.0 | ||||||
Location of target site | 3'UTR | ||||||
Tools used in this research | TargetScan , miRTarCLIP , Piranha | ||||||
Original Description (Extracted from the article) |
...
"PAR-CLIP data was present in GSM1065669. RNA binding protein: AGO1. Condition:4-thiouridine
... - Memczak S; Jens M; Elefsinioti A; Torti F; et al., 2013, Nature. |
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miRNA-target interactions (Provided by authors) |
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Article |
- Memczak S; Jens M; Elefsinioti A; Torti F; et al. - Nature, 2013
Circular RNAs (circRNAs) in animals are an enigmatic class of RNA with unknown function. To explore circRNAs systematically, we sequenced and computationally analysed human, mouse and nematode RNA. We detected thousands of well-expressed, stable circRNAs, often showing tissue/developmental-stage-specific expression. Sequence analysis indicated important regulatory functions for circRNAs. We found that a human circRNA, antisense to the cerebellar degeneration-related protein 1 transcript (CDR1as), is densely bound by microRNA (miRNA) effector complexes and harbours 63 conserved binding sites for the ancient miRNA miR-7. Further analyses indicated that CDR1as functions to bind miR-7 in neuronal tissues. Human CDR1as expression in zebrafish impaired midbrain development, similar to knocking down miR-7, suggesting that CDR1as is a miRNA antagonist with a miRNA-binding capacity ten times higher than any other known transcript. Together, our data provide evidence that circRNAs form a large class of post-transcriptional regulators. Numerous circRNAs form by head-to-tail splicing of exons, suggesting previously unrecognized regulatory potential of coding sequences.
LinkOut: [PMID: 23446348]
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Experimental Support 4 for Functional miRNA-Target Interaction | |
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miRNA:Target | ---- |
Validation Method |
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Conditions | MCF7 |
Location of target site | 3'UTR |
Tools used in this research | TargetScan , miRTarCLIP , Piranha |
Original Description (Extracted from the article) |
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PAR-CLIP data was present in SRR1045082. RNA binding protein: AGO2. Condition:Untreated
... - Farazi TA; Ten Hoeve JJ; Brown M; et al., 2014, Genome biology. |
Article |
- Farazi TA; Ten Hoeve JJ; Brown M; et al. - Genome biology, 2014
BACKGROUND: Various microRNAs (miRNAs) are up- or downregulated in tumors. However, the repression of cognate miRNA targets responsible for the phenotypic effects of this dysregulation in patients remains largely unexplored. To define miRNA targets and associated pathways, together with their relationship to outcome in breast cancer, we integrated patient-paired miRNA-mRNA expression data with a set of validated miRNA targets and pathway inference. RESULTS: To generate a biochemically-validated set of miRNA-binding sites, we performed argonaute-2 photoactivatable-ribonucleoside-enhanced crosslinking and immunoprecipitation (AGO2-PAR-CLIP) in MCF7 cells. We then defined putative miRNA-target interactions using a computational model, which ranked and selected additional TargetScan-predicted interactions based on features of our AGO2-PAR-CLIP binding-site data. We subselected modeled interactions according to the abundance of their constituent miRNA and mRNA transcripts in tumors, and we took advantage of the variability of miRNA expression within molecular subtypes to detect miRNA repression. Interestingly, our data suggest that miRNA families control subtype-specific pathways; for example, miR-17, miR-19a, miR-25, and miR-200b show high miRNA regulatory activity in the triple-negative, basal-like subtype, whereas miR-22 and miR-24 do so in the HER2 subtype. An independent dataset validated our findings for miR-17 and miR-25, and showed a correlation between the expression levels of miR-182 targets and overall patient survival. Pathway analysis associated miR-17, miR-19a, and miR-200b with leukocyte transendothelial migration. CONCLUSIONS: We combined PAR-CLIP data with patient expression data to predict regulatory miRNAs, revealing potential therapeutic targets and prognostic markers in breast cancer.
LinkOut: [PMID: 24398324]
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Experimental Support 5 for Functional miRNA-Target Interaction | |
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miRNA:Target | ---- |
Validation Method |
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Conditions | MCF7 , BT474 |
Location of target site | 3'UTR |
Tools used in this research | TargetScan , miRTarCLIP , Piranha |
Original Description (Extracted from the article) |
...
HITS-CLIP data was present in GSM1395164. RNA binding protein: AGO. Condition:MCF7 AGO HITS-CLIP Replicate 2
HITS-CLIP data was present in GSM1395166. RNA binding protein: AGO. Condition:BT474 AGO HITS-CLIP Replicate 1
HITS-CLIP data was present in GSM1395167. RNA binding protein: AGO. Condition:BT474 AGO HITS-CLIP Replicate 2
HITS-CLIP data was present in GSM1395168. RNA binding protein: AGO. Condition:BT474 AGO HITS-CLIP Replicate 3
... - Pillai MM; Gillen AE; Yamamoto TM; Kline E; et al., 2014, Breast cancer research and treatment. |
Article |
- Pillai MM; Gillen AE; Yamamoto TM; Kline E; et al. - Breast cancer research and treatment, 2014
miRNAs regulate the expression of genes in both normal physiology and disease. While miRNAs have been demonstrated to play a pivotal role in aspects of cancer biology, these reports have generally focused on the regulation of single genes. Such single-gene approaches have significant limitations, relying on miRNA expression levels and heuristic predictions of mRNA-binding sites. This results in only circumstantial evidence of miRNA-target interaction and typically leads to large numbers of false positive predictions. Here, we used a genome-wide approach (high-throughput sequencing of RNA isolated by crosslinking immunoprecipitation, HITS-CLIP) to define direct miRNA-mRNA interactions in three breast cancer subtypes (estrogen receptor positive, Her2 amplified, and triple negative). Focusing on steroid receptor signaling, we identified two novel regulators of the ER pathway (miR-9-5p and miR-193a/b-3p), which together target multiple genes involved in ER signaling. Moreover, this approach enabled the definition of miR-9-5p as a global regulator of steroid receptor signaling in breast cancer. We show that miRNA targets and networks defined by HITS-CLIP under physiologic conditions are predictive of patient outcomes and provide global insight into miRNA regulation in breast cancer.
LinkOut: [PMID: 24906430]
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Experimental Support 6 for Functional miRNA-Target Interaction | |
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miRNA:Target | ---- |
Validation Method |
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Conditions | HCT116 |
Location of target site | 3'UTR |
Tools used in this research | TargetScan , miRTarCLIP , Piranha |
Original Description (Extracted from the article) |
...
PAR-CLIP data was present in ERX177629. RNA binding protein: AGO2. Condition:KO_D_AGO_CLIP_4_7
PAR-CLIP data was present in ERX177633. RNA binding protein: AGO2. Condition:KO_D_AGO_CLIP_4_11
PAR-CLIP data was present in ERX177602. RNA binding protein: AGO2. Condition:KO_V_AGO_CLIP_2_4
PAR-CLIP data was present in ERX177606. RNA binding protein: AGO2. Condition:KO_V_AGO_CLIP_2_8
... - Krell J; Stebbing J; Carissimi C; Dabrowska et al., 2016, Genome research. |
Article |
- Krell J; Stebbing J; Carissimi C; Dabrowska et al. - Genome research, 2016
DNA damage activates TP53-regulated surveillance mechanisms that are crucial in suppressing tumorigenesis. TP53 orchestrates these responses directly by transcriptionally modulating genes, including microRNAs (miRNAs), and by regulating miRNA biogenesis through interacting with the DROSHA complex. However, whether the association between miRNAs and AGO2 is regulated following DNA damage is not yet known. Here, we show that, following DNA damage, TP53 interacts with AGO2 to induce or reduce AGO2's association of a subset of miRNAs, including multiple let-7 family members. Furthermore, we show that specific mutations in TP53 decrease rather than increase the association of let-7 family miRNAs, reducing their activity without preventing TP53 from interacting with AGO2. This is consistent with the oncogenic properties of these mutants. Using AGO2 RIP-seq and PAR-CLIP-seq, we show that the DNA damage-induced increase in binding of let-7 family members to the RISC complex is functional. We unambiguously determine the global miRNA-mRNA interaction networks involved in the DNA damage response, validating them through the identification of miRNA-target chimeras formed by endogenous ligation reactions. We find that the target complementary region of the let-7 seed tends to have highly fixed positions and more variable ones. Additionally, we observe that miRNAs, whose cellular abundance or differential association with AGO2 is regulated by TP53, are involved in an intricate network of regulatory feedback and feedforward circuits. TP53-mediated regulation of AGO2-miRNA interaction represents a new mechanism of miRNA regulation in carcinogenesis.
LinkOut: [PMID: 26701625]
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Experimental Support 7 for Functional miRNA-Target Interaction | |
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miRNA:Target | ---- |
Validation Method |
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Conditions | Prostate Tissue |
Location of target site | 3'UTR |
Tools used in this research | TargetScan , miRTarCLIP , Piranha |
Original Description (Extracted from the article) |
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PAR-CLIP data was present in SRX1760641. RNA binding protein: AGO2. Condition:AGO-CLIP-LNCaP-MDV_B
... - Hamilton MP; Rajapakshe KI; Bader DA; Cerne et al., 2016, Neoplasia (New York, N.Y.). |
Article |
- Hamilton MP; Rajapakshe KI; Bader DA; Cerne et al. - Neoplasia (New York, N.Y.), 2016
MicroRNA (miRNA) deregulation in prostate cancer (PCa) contributes to PCa initiation and metastatic progression. To comprehensively define the cancer-associated changes in miRNA targeting and function in commonly studied models of PCa, we performed photoactivatable ribonucleoside-enhanced cross-linking immunoprecipitation of the Argonaute protein in a panel of PCa cell lines modeling different stages of PCa progression. Using this comprehensive catalogue of miRNA targets, we analyzed miRNA targeting on known drivers of PCa and examined tissue-specific and stage-specific pathway targeting by miRNAs. We found that androgen receptor is the most frequently targeted PCa oncogene and that miR-148a targets the largest number of known PCa drivers. Globally, tissue-specific and stage-specific changes in miRNA targeting are driven by homeostatic response to active oncogenic pathways. Our findings indicate that, even in advanced PCa, the miRNA pool adapts to regulate continuing alterations in the cancer genome to balance oncogenic molecular changes. These findings are important because they are the first to globally characterize miRNA changes in PCa and demonstrate how the miRNA target spectrum responds to staged tumorigenesis.
LinkOut: [PMID: 27292025]
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Experimental Support 8 for Functional miRNA-Target Interaction | |
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miRNA:Target | ---- |
Validation Method |
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Conditions | Cardiac Tissues |
Location of target site | 3'UTR |
Tools used in this research | TargetScan , miRTarCLIP , Piranha |
Original Description (Extracted from the article) |
...
HITS-CLIP data was present in GSM2202480. RNA binding protein: AGO2. Condition:S5_LV_36yo_Male_AGO2_bound_RNA
... - Spengler RM; Zhang X; Cheng C; McLendon JM; et al., 2016, Nucleic acids research. |
Article |
Elucidation of transcriptome-wide microRNA binding sites in human cardiac tissues by Ago2 HITS-CLIP.
- Spengler RM; Zhang X; Cheng C; McLendon JM; et al.- Nucleic acids research, 2016
MicroRNAs (miRs) have emerged as key biological effectors in human health and disease. These small noncoding RNAs are incorporated into Argonaute (Ago) proteins, where they direct post-transcriptional gene silencing via base-pairing with target transcripts. Although miRs have become intriguing biological entities and attractive therapeutic targets, the translational impacts of miR research remain limited by a paucity of empirical miR targeting data, particularly in human primary tissues. Here, to improve our understanding of the diverse roles miRs play in cardiovascular function and disease, we applied high-throughput methods to globally profile miR:target interactions in human heart tissues. We deciphered Ago2:RNA interactions using crosslinking immunoprecipitation coupled with high-throughput sequencing (HITS-CLIP) to generate the first transcriptome-wide map of miR targeting events in human myocardium, detecting 4000 cardiac Ago2 binding sites across >2200 target transcripts. Our initial exploration of this interactome revealed an abundance of miR target sites in gene coding regions, including several sites pointing to new miR-29 functions in regulating cardiomyocyte calcium, growth and metabolism. Also, we uncovered several clinically-relevant interactions involving common genetic variants that alter miR targeting events in cardiomyopathy-associated genes. Overall, these data provide a critical resource for bolstering translational miR research in heart, and likely beyond.
LinkOut: [PMID: 27418678]
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CLIP-seq Support 1 for dataset GSM1395164 | |
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Method / RBP | HITS-CLIP / AGO |
Cell line / Condition | MCF7 / MCF7 AGO HITS-CLIP Replicate 2 |
Location of target site | ENST00000359376.3 | 3UTR | GAUGUGAGGGCGAUCUGGCUGCGACAUCUGUCACCCCAUUGAUCGCCAGGGUUGAUUCGGCUGAUCUGGCUGGCUAGG |
Tools used in this analysis | TargetScan, miRTarCLIP, and Piranha |
Article / Accession Series | PMID: 24906430 / GSE57855 |
CLIP-seq Viewer | Link |
CLIP-seq Support 2 for dataset GSM1395166 | |
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Method / RBP | HITS-CLIP / AGO |
Cell line / Condition | BT474 / BT474 AGO HITS-CLIP Replicate 1 |
Location of target site | ENST00000359376.3 | 3UTR | GAUGUGAGGGCGAUCUGGCUGCGACAUCUGUCACCCCAUUGAUCGCCAGGGUUGAUUCGGCUGAUCUGGCUGGCUAGGUGG |
Tools used in this analysis | TargetScan, miRTarCLIP, and Piranha |
Article / Accession Series | PMID: 24906430 / GSE57855 |
CLIP-seq Viewer | Link |
CLIP-seq Support 3 for dataset GSM1395167 | |
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Method / RBP | HITS-CLIP / AGO |
Cell line / Condition | BT474 / BT474 AGO HITS-CLIP Replicate 2 |
Location of target site | ENST00000359376.3 | 3UTR | GGAUGUGAGGGCGAUCUGGCUGCGACAUCUGUCACCCCAUUGAUCGCCAGGGUUGAUUCGGCUGAUCUGGCUGGCUAGG |
Tools used in this analysis | TargetScan, miRTarCLIP, and Piranha |
Article / Accession Series | PMID: 24906430 / GSE57855 |
CLIP-seq Viewer | Link |
CLIP-seq Support 4 for dataset GSM1395168 | |
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Method / RBP | HITS-CLIP / AGO |
Cell line / Condition | BT474 / BT474 AGO HITS-CLIP Replicate 3 |
Location of target site | ENST00000359376.3 | 3UTR | GGAUGUGAGGGCGAUCUGGCUGCGACAUCUGUCACCCCAUUGAUCGCCAGGGUUGAUUCGGCUGAUCUGGCUGGCUAGG |
Tools used in this analysis | TargetScan, miRTarCLIP, and Piranha |
Article / Accession Series | PMID: 24906430 / GSE57855 |
CLIP-seq Viewer | Link |
CLIP-seq Support 5 for dataset GSM1013106 | |
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Method / RBP | HITS-CLIP / AGO |
Cell line / Condition | HS27a / HS27a-replicate-2 |
Location of target site | ENST00000359376.3 | 3UTR | GGAUGUGAGGGCGAUCUGGCUGCGACAUCUGUCACCCCAUUGAUCGCCAGGGUUGAUUCGGCUGAUCUGGCUGGCUAGG |
Tools used in this analysis | TargetScan, miRTarCLIP, and Piranha |
Article / Accession Series | PMID: 24038734 / GSE41272 |
CLIP-seq Viewer | Link |
CLIP-seq Support 6 for dataset GSM1013110 | |
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Method / RBP | HITS-CLIP / AGO |
Cell line / Condition | hMSC / hMSC-replicate-1 |
Location of target site | ENST00000359376.3 | 3UTR | UCUGGCUGCGACAUCUGUCACCCCAUUGAUCGCCAGGGUUGAUUCGGCUGAUCUGGCUGGCUAGG |
Tools used in this analysis | TargetScan, miRTarCLIP, and Piranha |
Article / Accession Series | PMID: 24038734 / GSE41272 |
CLIP-seq Viewer | Link |
CLIP-seq Support 7 for dataset GSM1013117 | |
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Method / RBP | HITS-CLIP / AGO |
Cell line / Condition | TrHBMEC / TrHBMEC-replicate-2 |
Location of target site | ENST00000359376.3 | 3UTR | UCUGGCUGCGACAUCUGUCACCCCAUUGAUCGCCAGGGUUGAUUCGGCUGAUCUGGCUGGCUAG |
Tools used in this analysis | TargetScan, miRTarCLIP, and Piranha |
Article / Accession Series | PMID: 24038734 / GSE41272 |
CLIP-seq Viewer | Link |
CLIP-seq Support 8 for dataset GSM1013118 | |
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Method / RBP | HITS-CLIP / AGO |
Cell line / Condition | TrHBMEC / TrHBMEC-replicate-3 |
Location of target site | ENST00000359376.3 | 3UTR | UGAGGGCGAUCUGGCUGCGACAUCUGUCACCCCAUUGAUCGCCAGGGUUGAUUCGGCUGAUCUGGCUGGCUAGG |
Tools used in this analysis | TargetScan, miRTarCLIP, and Piranha |
Article / Accession Series | PMID: 24038734 / GSE41272 |
CLIP-seq Viewer | Link |
CLIP-seq Support 9 for dataset GSM545215 | |
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Method / RBP | PAR-CLIP / AGO4 |
Cell line / Condition | HEK293 / Control |
Location of target site | ENST00000359376.3 | 3UTR | GGGCGAUCUGGCUGCGACAUCUGUCACCCCAUUGAUCGCCAGGGUUGAUUCGGCUGAUCUGGCUGGCUAGGUG |
Tools used in this analysis | TargetScan, miRTarCLIP, and Piranha |
Article / Accession Series | PMID: 20371350 / GSE21578 |
CLIP-seq Viewer | Link |
CLIP-seq Support 10 for dataset SRR359787 | |
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Method / RBP | PAR-CLIP / AGO2 |
Cell line / Condition | hESCs (WA-09) / 4-thiouridine, RNase T1 |
Location of target site | ENST00000359376.3 | 3UTR | AGGGCGAUCUGGCUGCGACAUCUGUCACCCCAUUGAUCGCCAGGGUUGAUUCGGCU |
Tools used in this analysis | TargetScan, miRTarCLIP, and Piranha |
Article / Accession Series | PMID: 22012620 / SRX103431 |
CLIP-seq Viewer | Link |
CLIP-seq Support 11 for dataset GSM1065669 | |
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Method / RBP | PAR-CLIP / AGO1 |
Cell line / Condition | HEK293 / 4-thiouridine, ML_MM_8 |
Location of target site | ENST00000359376.3 | 3UTR | AUCUGGCUGCGACAUCUGUCACCCCAUUGAUCGCCAG |
Tools used in this analysis | TargetScan, miRTarCLIP, and Piranha |
Article / Accession Series | PMID: 23446348 / GSE43573 |
CLIP-seq Viewer | Link |
CLIP-seq Support 12 for dataset SRR1045082 | |
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Method / RBP | PAR-CLIP / AGO2 |
Cell line / Condition | MCF7 / Untreated |
Location of target site | ENST00000359376.3 | 3UTR | CGAUCUGGCUGCGACAUCUGUCACCCCAUUGAUCGCCAGGGUUGAUUCGGCUGAUCUGGCUGGCUAGGUGGGUGUCCCCUUCCUACCUCACCGCUCCAUGUGCGUCCCUCCCGAAGCUGC |
Tools used in this analysis | TargetScan, miRTarCLIP, and Piranha |
Article / Accession Series | PMID: 24398324 / SRX388831 |
CLIP-seq Viewer | Link |
MiRNA-Target Expression Profile | |||||||
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MiRNA-Target Expression Profile (TCGA) | |||||||
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ID![]() |
Target | Description | Validation methods |
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Strong evidence | Less strong evidence | |||||||||||
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MIRT066215 | MARCH9 | membrane associated ring-CH-type finger 9 | ![]() |
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2 | 2 | ||||||
MIRT074413 | TNRC6A | trinucleotide repeat containing 6A | ![]() |
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2 | 2 | ||||||
MIRT125300 | MID1IP1 | MID1 interacting protein 1 | ![]() |
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2 | 2 | ||||||
MIRT153951 | NCOA3 | nuclear receptor coactivator 3 | ![]() |
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2 | 2 | ||||||
MIRT452776 | FAM136A | family with sequence similarity 136 member A | ![]() |
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2 | 2 | ||||||
MIRT452977 | CABP4 | calcium binding protein 4 | ![]() |
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2 | 2 | ||||||
MIRT454128 | FOXRED2 | FAD dependent oxidoreductase domain containing 2 | ![]() |
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2 | 2 | ||||||
MIRT455242 | DDX39B | DExD-box helicase 39B | ![]() |
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2 | 10 | ||||||
MIRT459007 | UQCRH | ubiquinol-cytochrome c reductase hinge protein | ![]() |
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2 | 2 | ||||||
MIRT459463 | MUC17 | mucin 17, cell surface associated | ![]() |
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2 | 4 | ||||||
MIRT460871 | UBE2S | ubiquitin conjugating enzyme E2 S | ![]() |
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2 | 2 | ||||||
MIRT461264 | COX10 | COX10, heme A:farnesyltransferase cytochrome c oxidase assembly factor | ![]() |
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2 | 2 | ||||||
MIRT464540 | UBTF | upstream binding transcription factor, RNA polymerase I | ![]() |
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2 | 2 | ||||||
MIRT465268 | TRIM28 | tripartite motif containing 28 | ![]() |
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2 | 2 | ||||||
MIRT465871 | TMEM43 | transmembrane protein 43 | ![]() |
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2 | 4 | ||||||
MIRT466228 | TMED10 | transmembrane p24 trafficking protein 10 | ![]() |
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2 | 2 | ||||||
MIRT468417 | SETD1B | SET domain containing 1B | ![]() |
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2 | 2 | ||||||
MIRT468684 | SEC22C | SEC22 homolog C, vesicle trafficking protein | ![]() |
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2 | 4 | ||||||
MIRT473399 | MDM4 | MDM4, p53 regulator | ![]() |
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2 | 2 | ||||||
MIRT473517 | MAX | MYC associated factor X | ![]() |
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2 | 2 | ||||||
MIRT474511 | KLHDC8A | kelch domain containing 8A | ![]() |
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2 | 2 | ||||||
MIRT475801 | HDGF | heparin binding growth factor | ![]() |
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2 | 2 | ||||||
MIRT479493 | CDH6 | cadherin 6 | ![]() |
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2 | 2 | ||||||
MIRT480770 | BMP2 | bone morphogenetic protein 2 | ![]() |
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2 | 2 | ||||||
MIRT481418 | ASB6 | ankyrin repeat and SOCS box containing 6 | ![]() |
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2 | 2 | ||||||
MIRT482966 | CSTF2 | cleavage stimulation factor subunit 2 | ![]() |
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2 | 2 | ||||||
MIRT483380 | SPATA6 | spermatogenesis associated 6 | ![]() |
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2 | 4 | ||||||
MIRT483677 | CYP11A1 | cytochrome P450 family 11 subfamily A member 1 | ![]() |
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2 | 2 | ||||||
MIRT484328 | EPN1 | epsin 1 | ![]() |
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2 | 4 | ||||||
MIRT484963 | UCK1 | uridine-cytidine kinase 1 | ![]() |
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2 | 2 | ||||||
MIRT485908 | PGPEP1 | pyroglutamyl-peptidase I | ![]() |
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2 | 4 | ||||||
MIRT488149 | PRRC2B | proline rich coiled-coil 2B | ![]() |
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2 | 4 | ||||||
MIRT488943 | CYP2W1 | cytochrome P450 family 2 subfamily W member 1 | ![]() |
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2 | 6 | ||||||
MIRT491835 | ZBTB7A | zinc finger and BTB domain containing 7A | ![]() |
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2 | 4 | ||||||
MIRT493026 | NAA50 | N(alpha)-acetyltransferase 50, NatE catalytic subunit | ![]() |
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2 | 2 | ||||||
MIRT499374 | PLCG2 | phospholipase C gamma 2 | ![]() |
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2 | 11 | ||||||
MIRT499723 | USH1G | USH1 protein network component sans | ![]() |
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2 | 4 | ||||||
MIRT500349 | ZNF385A | zinc finger protein 385A | ![]() |
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2 | 2 | ||||||
MIRT509574 | HIST2H2AB | histone cluster 2 H2A family member b | ![]() |
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2 | 4 | ||||||
MIRT512794 | GLRX | glutaredoxin | ![]() |
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2 | 2 | ||||||
MIRT513291 | SETBP1 | SET binding protein 1 | ![]() |
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2 | 2 | ||||||
MIRT515697 | ZNF321P | zinc finger protein 321, pseudogene | ![]() |
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2 | 2 | ||||||
MIRT518255 | LEAP2 | liver enriched antimicrobial peptide 2 | ![]() |
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2 | 2 | ||||||
MIRT522026 | PAQR3 | progestin and adipoQ receptor family member 3 | ![]() |
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2 | 4 | ||||||
MIRT523169 | HIST3H3 | histone cluster 3 H3 | ![]() |
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2 | 2 | ||||||
MIRT524036 | DNAJC8 | DnaJ heat shock protein family (Hsp40) member C8 | ![]() |
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2 | 2 | ||||||
MIRT533476 | TRIM71 | tripartite motif containing 71 | ![]() |
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2 | 2 | ||||||
MIRT541488 | ADM | adrenomedullin | ![]() |
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2 | 2 | ||||||
MIRT553987 | SRPR | SRP receptor alpha subunit | ![]() |
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2 | 2 | ||||||
MIRT571445 | YKT6 | YKT6 v-SNARE homolog | ![]() |
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2 | 2 | ||||||
MIRT574889 | Plcg2 | phospholipase C, gamma 2 | ![]() |
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2 | 7 | ||||||
MIRT607544 | GLI2 | GLI family zinc finger 2 | ![]() |
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2 | 2 | ||||||
MIRT607688 | MAPK10 | mitogen-activated protein kinase 10 | ![]() |
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2 | 2 | ||||||
MIRT610072 | CRLF1 | cytokine receptor like factor 1 | ![]() |
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2 | 2 | ||||||
MIRT610573 | CACUL1 | CDK2 associated cullin domain 1 | ![]() |
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2 | 2 | ||||||
MIRT614041 | THBS2 | thrombospondin 2 | ![]() |
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2 | 2 | ||||||
MIRT626318 | LRTOMT | leucine rich transmembrane and O-methyltransferase domain containing | ![]() |
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2 | 2 | ||||||
MIRT634005 | RIF1 | replication timing regulatory factor 1 | ![]() |
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2 | 2 | ||||||
MIRT639619 | FGF19 | fibroblast growth factor 19 | ![]() |
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2 | 2 | ||||||
MIRT647343 | RPH3AL | rabphilin 3A like (without C2 domains) | ![]() |
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2 | 2 | ||||||
MIRT689704 | ATXN2 | ataxin 2 | ![]() |
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2 | 2 | ||||||
MIRT691170 | APOL6 | apolipoprotein L6 | ![]() |
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2 | 2 | ||||||
MIRT693165 | NPR1 | natriuretic peptide receptor 1 | ![]() |
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2 | 2 | ||||||
MIRT711727 | NUPL2 | nucleoporin like 2 | ![]() |
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2 | 2 | ||||||
MIRT711806 | ELN | elastin | ![]() |
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2 | 2 | ||||||
MIRT721546 | FXN | frataxin | ![]() |
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2 | 2 | ||||||
MIRT722979 | GDE1 | glycerophosphodiester phosphodiesterase 1 | ![]() |
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2 | 2 |
miRNA-Drug Resistance Associations | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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