pre-miRNA Information | |
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pre-miRNA | hsa-mir-29b-1 |
Genomic Coordinates | chr7: 130877459 - 130877539 |
Synonyms | MIRN29B1, miRNA29B1, MIR29B1 |
Description | Homo sapiens miR-29b-1 stem-loop |
Comment | Mourelatos et al. identified two copies of this sequence mapping to chromosome 7, and assigned the names mir-102-7.1 and mir-102-7.2 . Subsequent genome assemblies suggest the presence of only one miR-102 locus on chromosome 7. Human miR-102 is a homologue of mouse miR-29b (MIR:MI0000143) and so has been renamed here for consistency. |
RNA Secondary Structure | |
Associated Diseases | |
pre-miRNA | hsa-mir-29b-2 |
Genomic Coordinates | chr1: 207802443 - 207802523 |
Synonyms | MIRN29B2, mir-29b-2, MIR29B2 |
Description | Homo sapiens miR-29b-2 stem-loop |
Comment | This sequence was named mir-102-1 in reference . Human miR-102 is a homologue of mouse miR-29b (MIR:MI0000143) and so has been renamed here for consistency. |
RNA Secondary Structure | |
Associated Diseases |
Mature miRNA Information | ||||||||||||||||||||||
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Mature miRNA | hsa-miR-29b-3p | |||||||||||||||||||||
Sequence | 52| UAGCACCAUUUGAAAUCAGUGUU |74 | |||||||||||||||||||||
Evidence | Experimental | |||||||||||||||||||||
Experiments | Cloned | |||||||||||||||||||||
Editing Events in miRNAs |
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SNPs in miRNA |
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Putative Targets |
miRNA Expression profile | |
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Human miRNA Tissue Atlas | |
miRNAs in Extracellular Vesicles |
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Circulating MicroRNA Expression Profiling |
Gene Information | |||||||||||||||||||||
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Gene Symbol | VEGFA | ||||||||||||||||||||
Synonyms | MVCD1, VEGF, VPF | ||||||||||||||||||||
Description | vascular endothelial growth factor A | ||||||||||||||||||||
Transcript | NM_001025369 | ||||||||||||||||||||
Other Transcripts | NM_001025367 , NM_001025368 , NM_001025366 , NM_001025370 , NM_001033756 , NM_001171622 , NM_001171623 , NM_001171624 , NM_001171625 , NM_001171626 , NM_001171627 , NM_001171628 , NM_001171629 , NM_001171630 , NM_003376 | ||||||||||||||||||||
Expression | |||||||||||||||||||||
Putative miRNA Targets on VEGFA | |||||||||||||||||||||
3'UTR of VEGFA (miRNA target sites are highlighted) |
>VEGFA|NM_001025369|3'UTR 1 CAAGCCGAGGCGGTGAGCCGGGCAGGAGGAAGGAGCCTCCCTCAGGGTTTCGGGAACCAGATCTCTCACCAGGAAAGACT 81 GATACAGAACGATCGATACAGAAACCACGCTGCCGCCACCACACCATCACCATCGACAGAACAGTCCTTAATCCAGAAAC 161 CTGAAATGAAGGAAGAGGAGACTCTGCGCAGAGCACTTTGGGTCCGGAGGGCGAGACTCCGGCGGAAGCATTCCCGGGCG 241 GGTGACCCAGCACGGTCCCTCTTGGAATTGGATTCGCCATTTTATTTTTCTTGCTGCTAAATCACCGAGCCCGGAAGATT 321 AGAGAGTTTTATTTCTGGGATTCCTGTAGACACACCCACCCACATACATACATTTATATATATATATATTATATATATAT 401 AAAAATAAATATCTCTATTTTATATATATAAAATATATATATTCTTTTTTTAAATTAACAGTGCTAATGTTATTGGTGTC 481 TTCACTGGATGTATTTGACTGCTGTGGACTTGAGTTGGGAGGGGAATGTTCCCACTCAGATCCTGACAGGGAAGAGGAGG 561 AGATGAGAGACTCTGGCATGATCTTTTTTTTGTCCCACTTGGTGGGGCCAGGGTCCTCTCCCCTGCCCAGGAATGTGCAA 641 GGCCAGGGCATGGGGGCAAATATGACCCAGTTTTGGGAACACCGACAAACCCAGCCCTGGCGCTGAGCCTCTCTACCCCA 721 GGTCAGACGGACAGAAAGACAGATCACAGGTACAGGGATGAGGACACCGGCTCTGACCAGGAGTTTGGGGAGCTTCAGGA 801 CATTGCTGTGCTTTGGGGATTCCCTCCACATGCTGCACGCGCATCTCGCCCCCAGGGGCACTGCCTGGAAGATTCAGGAG 881 CCTGGGCGGCCTTCGCTTACTCTCACCTGCTTCTGAGTTGCCCAGGAGACCACTGGCAGATGTCCCGGCGAAGAGAAGAG 961 ACACATTGTTGGAAGAAGCAGCCCATGACAGCTCCCCTTCCTGGGACTCGCCCTCATCCTCTTCCTGCTCCCCTTCCTGG 1041 GGTGCAGCCTAAAAGGACCTATGTCCTCACACCATTGAAACCACTAGTTCTGTCCCCCCAGGAGACCTGGTTGTGTGTGT 1121 GTGAGTGGTTGACCTTCCTCCATCCCCTGGTCCTTCCCTTCCCTTCCCGAGGCACAGAGAGACAGGGCAGGATCCACGTG 1201 CCCATTGTGGAGGCAGAGAAAAGAGAAAGTGTTTTATATACGGTACTTATTTAATATCCCTTTTTAATTAGAAATTAAAA 1281 CAGTTAATTTAATTAAAGAGTAGGGTTTTTTTTCAGTATTCTTGGTTAATATTTAATTTCAACTATTTATGAGATGTATC 1361 TTTTGCTCTCTCTTGCTCTCTTATTTGTACCGGTTTTTGTATATAAAATTCATGTTTCCAATCTCTCTCTCCCTGATCGG 1441 TGACAGTCACTAGCTTATCTTGAACAGATATTTAATTTTGCTAACACTCAGCTCTGCCCTCCCCGATCCCCTGGCTCCCC 1521 AGCACACATTCCTTTGAAATAAGGTTTCAATATACATCTACATACTATATATATATTTGGCAACTTGTATTTGTGTGTAT 1601 ATATATATATATATGTTTATGTATATATGTGATTCTGATAAAATAGACATTGCTATTCTGTTTTTTATATGTAAAAACAA 1681 AACAAGAAAAAATAGAGAATTCTACATACTAAATCTCTCTCCTTTTTTAATTTTAATATTTGTTATCATTTATTTATTGG 1761 TGCTACTGTTTATCCGTAATAATTGTGGGGAAAAGATATTAACATCACGTCTTTGTCTCTAGTGCAGTTTTTCGAGATAT 1841 TCCGTAGTACATATTTATTTTTAAACAACGACAAAGAAATACAGATATATCTTAAAAAAAAAAAAGCATTTTGTATTAAA 1921 GAATTTAATTCTGATCTCAAAAAAAAAAAAAAAAAA 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 | Cos-7 |
Location of target site | 3'UTR |
Tools used in this research | FindTar |
Original Description (Extracted from the article) |
...
{This MTI is shown in Fig. 1 and Fig. 2}
... - Ye W; Lv Q; Wong CK; Hu S; Fu C; Hua Z; Cai et al., 2008, PloS one. |
Article |
- Ye W; Lv Q; Wong CK; Hu S; Fu C; Hua Z; Cai et al. - PloS one, 2008
MicroRNAs (miRNAs) guide posttranscriptional repression of mRNAs. Hundreds of miRNAs have been identified but the target identification of mammalian mRNAs is still a difficult task due to a poor understanding of the interaction between miRNAs and the miRNA recognizing element (MRE). In recent research, the importance of the 5' end of the miRNA:MRE duplex has been emphasized and the effect of the tail region addressed, but the role of the central loop has largely remained unexplored. Here we examined the effect of the loop region in miRNA:MRE duplexes and found that the location of the central loop is one of the important factors affecting the efficiency of gene regulation mediated by miRNAs. It was further determined that the addition of a loop score combining both location and size as a new criterion for predicting MREs and their cognate miRNAs significantly decreased the false positive rates and increased the specificity of MRE prediction.
LinkOut: [PMID: 18320040]
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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 | 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 GSM545216. RNA binding protein: AGO2. Condition:miR-124 transfection
... - Hafner M; Landthaler M; Burger L; Khorshid et al., 2010, Cell. |
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miRNA-target interactions (Provided by authors) |
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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 3 for Functional miRNA-Target Interaction | |
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miRNA:Target | ---- |
Validation Method |
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Conditions | HEK293 |
Disease | 7422.0 |
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 GSM714644. RNA binding protein: AGO2. Condition:completeT1
"PAR-CLIP data was present in GSM714645. RNA binding protein: AGO2. Condition:completeT1
... - Kishore S; Jaskiewicz L; Burger L; Hausser et al., 2011, Nature methods. |
Article |
- Kishore S; Jaskiewicz L; Burger L; Hausser et al. - Nature methods, 2011
Cross-linking and immunoprecipitation (CLIP) is increasingly used to map transcriptome-wide binding sites of RNA-binding proteins. We developed a method for CLIP data analysis, and applied it to compare CLIP with photoactivatable ribonucleoside-enhanced CLIP (PAR-CLIP) and to uncover how differences in cross-linking and ribonuclease digestion affect the identified sites. We found only small differences in accuracies of these methods in identifying binding sites of HuR, which binds low-complexity sequences, and Argonaute 2, which has a complex binding specificity. We found that cross-link-induced mutations led to single-nucleotide resolution for both PAR-CLIP and CLIP. Our results confirm the expectation from original CLIP publications that RNA-binding proteins do not protect their binding sites sufficiently under the denaturing conditions used during the CLIP procedure, and we show that extensive digestion with sequence-specific RNases strongly biases the recovered binding sites. This bias can be substantially reduced by milder nuclease digestion conditions.
LinkOut: [PMID: 21572407]
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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 | 4T1 |
Disease | breast cancer |
Location of target site | 3'UTR |
Tools used in this research | previous_study |
Original Description (Extracted from the article) |
...
The miR-29b seed sequence is in red and the complementary binding sites are in green. The mutations generated within the 3' UTRs for c are in purple. The wild-type and mutant 3 ' UTRs of the indicated miR-29b targets were cloned into dual luciferase reporters and co-transfected with miR-29b or cel-67 control mimic.
miR-29b is induced by GATA3
... - Chou J; Lin JH; Brenot A; Kim JW; Provot S; Werb Z, 2013, Nature cell biology. |
Article |
- Chou J; Lin JH; Brenot A; Kim JW; Provot S; Werb Z - Nature cell biology, 2013
Despite advances in our understanding of breast cancer, patients with metastatic disease have poor prognoses. GATA3 is a transcription factor that specifies and maintains mammary luminal epithelial cell fate, and its expression is lost in breast cancer, correlating with a worse prognosis in human patients. Here, we show that GATA3 promotes differentiation, suppresses metastasis and alters the tumour microenvironment in breast cancer by inducing microRNA-29b (miR-29b) expression. Accordingly, miR-29b is enriched in luminal breast cancers and loss of miR-29b, even in GATA3-expressing cells, increases metastasis and promotes a mesenchymal phenotype. Mechanistically, miR-29b inhibits metastasis by targeting a network of pro-metastatic regulators involved in angiogenesis, collagen remodelling and proteolysis, including VEGFA, ANGPTL4, PDGF, LOX and MMP9, and targeting ITGA6, ITGB1 and TGFB, thereby indirectly affecting differentiation and epithelial plasticity. The discovery that a GATA3-miR-29b axis regulates the tumour microenvironment and inhibits metastasis opens up possibilities for therapeutic intervention in breast cancer.
LinkOut: [PMID: 23354167]
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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 | TZM-bl |
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 GSM1462574. RNA binding protein: AGO2. Condition:TZM-bl ami BaL
... - Whisnant AW; Bogerd HP; Flores O; Ho P; et al., 2013, mBio. |
Article |
- Whisnant AW; Bogerd HP; Flores O; Ho P; et al. - mBio, 2013
UNLABELLED: The question of how HIV-1 interfaces with cellular microRNA (miRNA) biogenesis and effector mechanisms has been highly controversial. Here, we first used deep sequencing of small RNAs present in two different infected cell lines (TZM-bl and C8166) and two types of primary human cells (CD4(+) peripheral blood mononuclear cells [PBMCs] and macrophages) to unequivocally demonstrate that HIV-1 does not encode any viral miRNAs. Perhaps surprisingly, we also observed that infection of T cells by HIV-1 has only a modest effect on the expression of cellular miRNAs at early times after infection. Comprehensive analysis of miRNA binding to the HIV-1 genome using the photoactivatable ribonucleoside-induced cross-linking and immunoprecipitation (PAR-CLIP) technique revealed several binding sites for cellular miRNAs, a subset of which were shown to be capable of mediating miRNA-mediated repression of gene expression. However, the main finding from this analysis is that HIV-1 transcripts are largely refractory to miRNA binding, most probably due to extensive viral RNA secondary structure. Together, these data demonstrate that HIV-1 neither encodes viral miRNAs nor strongly influences cellular miRNA expression, at least early after infection, and imply that HIV-1 transcripts have evolved to avoid inhibition by preexisting cellular miRNAs by adopting extensive RNA secondary structures that occlude most potential miRNA binding sites. IMPORTANCE: MicroRNAs (miRNAs) are a ubiquitous class of small regulatory RNAs that serve as posttranscriptional regulators of gene expression. Previous work has suggested that HIV-1 might subvert the function of the cellular miRNA machinery by expressing viral miRNAs or by dramatically altering the level of cellular miRNA expression. Using very sensitive approaches, we now demonstrate that neither of these ideas is in fact correct. Moreover, HIV-1 transcripts appear to largely avoid regulation by cellular miRNAs by adopting an extensive RNA secondary structure that occludes the ability of cellular miRNAs to interact with viral mRNAs. Together, these data suggest that HIV-1, rather than seeking to control miRNA function in infected cells, has instead evolved a mechanism to become largely invisible to cellular miRNA effector mechanisms.
LinkOut: [PMID: 23592263]
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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 | RL-95-2 , HEC-1-B |
Disease | 0.0 |
Location of target site | 3'UTR |
Original Description (Extracted from the article) |
...
"Compared with the adjacent normal tissues
... - Chen HX; Xu XX; Tan BZ; Zhang Z; Zhou XD, 2017, Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology. |
Article |
- Chen HX; Xu XX; Tan BZ; Zhang Z; Zhou XD - Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology, 2017
OBJECTIVE: The purpose of this study is to explore the effects of microRNA-29b (miR-29b) regulating MAPK/ERK and PI3K/Akt signaling pathways on angiogenesis in endometrial carcinoma (EC) by targeting VEGFA. METHODS: Between February 2013 and April 2015, 126 EC patients admitted to the Second Affiliated Hospital of Nanchang University were randomly selected, with 126 EC tissues and the corresponding adjacent normal tissues collected after surgery. The human EC cell lines RL-95-2 and HEC-1-B and human endometrial cells were assigned to the normal group (human endometrial cells), the blank group (untransfected RL-95-2 or HEC-1-B cells), the pMIR-control group (RL-95-2 or HEC-1-B cells transfected with an empty vector), the pMIR-miR-29b group (RL-95-2 or HEC-1-B cells transfected with the miR-29b plasmid), LNA-control group (RL-95-2 or HEC-1-B cells transfected with an oligonucleotide inhibitors control), the LNA-miR-29b inhibitors group (RL-95-2 or HEC-1-B cells transfected with miRCURY LNATM miR-29b inhibitors), the LNA-miR-29b inhibitors + PD98059 group (RL-95-2 or HEC-1-B cells transfected with miRCURY LNATM miR-29b inhibitors and PD98059, an inhibitor of the MAPK/ERK signaling pathway) and the LNA-miR-29b inhibitors + wortmannin group (RL-95-2 or HEC-1-B cells transfected with miRCURY LNATM miR-29b inhibitors and wortmannin, an inhibitor of the PI3K/Akt signaling pathway). qRT-PCR and Western blotting were conducted to detect the miR-29b expression and the mRNA and protein expressions of VEGFA, ERK, Akt, mTOR and Bcl-2. Immunohistochemistry (IHC) was performed to determine the microvessel density (MVD) expression in the EC tissues, adjacent normal tissues and nude-mice. RESULTS: Compared with the adjacent normal tissues, miR-29b expression was down-regulated, the mRNA and protein expressions of VEGFA, ERK, Akt, mTOR and Bcl-2 were up-regulated, and MVD expression was increased in the EC tissues. Compared with the normal group, miR-29b expression was down-regulated, while the mRNA and protein expressions of VEGFA, ERK, Akt, mTOR and Bcl-2 were up-regulated in the other groups. Compared with the blank, pMIR-control and LNA-control groups, miR-29b expression was increased, while mRNA and protein expressions of VEGFA, ERK, Akt, mTOR and Bcl-2 were decreased in the pMIR-miR-29b group. The LNA-miR-29b inhibitors group exhibited elevated miR-29b expression and decreased mRNA and protein expressions of VEGFA, ERK, Akt, mTOR and Bcl-2 (All P < 0.05). Additionally, miR-29b expression was reduced in the LNA-miR-29b inhibitors + PD98059 and LNA-miR-29b inhibitors + wortmannin groups. In comparison to the normal group, MVD expression was elevated in the other groups. Compared with the blank, pMIR-control, LNA-control, LNA-miR-29b inhibitors + PD98059 and LNA-miR-29b inhibitors + wortmannin groups, MVD expression was decreased in the pMIR-miR-29b group but increased in the LNA-miR-29b inhibitors group. CONCLUSION: Our results indicate that miR-29b negatively modulates the MAPK/ERK and PI3K/Akt signaling pathways to inhibit angiogenesis in EC by targeting VEGFA.
LinkOut: [PMID: 28222438]
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CLIP-seq Support 1 for dataset GSM545216 | |
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Method / RBP | PAR-CLIP / AGO2 |
Cell line / Condition | HEK293 / miR-124 transfection |
Location of target site | ENST00000372067.3 | 3UTR | UUAUCAUUUAUUUAUUGGUGCUACU |
Tools used in this analysis | TargetScan, miRTarCLIP, and Piranha |
Article / Accession Series | PMID: 20371350 / GSE21578 |
CLIP-seq Viewer | Link |
CLIP-seq Support 2 for dataset GSM714644 | |
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Method / RBP | PAR-CLIP / AGO2 |
Cell line / Condition | HEK293 / completeT1, repA |
Location of target site | ENST00000372067.3 | 3UTR | UUAUCAUUUAUUUAUUGGUGCUACUG |
Tools used in this analysis | TargetScan, miRTarCLIP, and Piranha |
Article / Accession Series | PMID: 21572407 / GSE28865 |
CLIP-seq Viewer | Link |
CLIP-seq Support 3 for dataset GSM714645 | |
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Method / RBP | PAR-CLIP / AGO2 |
Cell line / Condition | HEK293 / completeT1, repB |
Location of target site | ENST00000372067.3 | 3UTR | UUAUCAUUUAUUUAUUGGUGCUACUG |
Tools used in this analysis | TargetScan, miRTarCLIP, and Piranha |
Article / Accession Series | PMID: 21572407 / GSE28865 |
CLIP-seq Viewer | Link |
CLIP-seq Support 4 for dataset GSM1462574 | |
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Method / RBP | PAR-CLIP / AGO2 |
Cell line / Condition | TZM-bl / TZM-bl ami BaL |
Location of target site | ENST00000372067.3 | 3UTR | UUAUCAUUUAUUUAUUGGUGCUACUG |
Tools used in this analysis | TargetScan, miRTarCLIP, and Piranha |
Article / Accession Series | PMID: 23592263 / GSE59944 |
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 | |||||||||
Strong evidence | Less strong evidence | |||||||||||
MIRT000095 | TGFB3 | transforming growth factor beta 3 | 2 | 1 | ||||||||
MIRT000096 | HDAC4 | histone deacetylase 4 | 4 | 4 | ||||||||
MIRT000097 | CTNNBIP1 | catenin beta interacting protein 1 | 4 | 4 | ||||||||
MIRT000098 | COL5A3 | collagen type V alpha 3 chain | 2 | 2 | ||||||||
MIRT000099 | COL4A2 | collagen type IV alpha 2 chain | 2 | 2 | ||||||||
MIRT000100 | COL1A1 | collagen type I alpha 1 chain | 8 | 8 | ||||||||
MIRT000101 | ACVR2A | activin A receptor type 2A | 1 | 1 | ||||||||
MIRT000445 | SP1 | Sp1 transcription factor | 5 | 6 | ||||||||
MIRT000684 | CDK6 | cyclin dependent kinase 6 | 6 | 5 | ||||||||
MIRT000930 | BACE1 | beta-secretase 1 | 3 | 1 | ||||||||
MIRT002310 | SFPQ | splicing factor proline and glutamine rich | 3 | 1 | ||||||||
MIRT002316 | DNAJB11 | DnaJ heat shock protein family (Hsp40) member B11 | 3 | 1 | ||||||||
MIRT003026 | DNMT3B | DNA methyltransferase 3 beta | 4 | 7 | ||||||||
MIRT003029 | DNMT3A | DNA methyltransferase 3 alpha | 5 | 9 | ||||||||
MIRT003287 | MCL1 | MCL1, BCL2 family apoptosis regulator | 7 | 20 | ||||||||
MIRT003290 | BCL2 | BCL2, apoptosis regulator | 4 | 3 | ||||||||
MIRT003661 | DNMT1 | DNA methyltransferase 1 | 4 | 2 | ||||||||
MIRT003736 | S100B | S100 calcium binding protein B | 3 | 1 | ||||||||
MIRT003813 | VEGFA | vascular endothelial growth factor A | 9 | 9 | ||||||||
MIRT004308 | ESR1 | estrogen receptor 1 | 2 | 1 | ||||||||
MIRT004312 | NCOA3 | nuclear receptor coactivator 3 | 2 | 1 | ||||||||
MIRT004419 | TET1 | tet methylcytosine dioxygenase 1 | 4 | 2 | ||||||||
MIRT004510 | TCL1A | T-cell leukemia/lymphoma 1A | 5 | 4 | ||||||||
MIRT005381 | Mmp15 | matrix metallopeptidase 15 | 3 | 1 | ||||||||
MIRT005383 | MMP15 | matrix metallopeptidase 15 | 2 | 1 | ||||||||
MIRT005385 | MMP24 | matrix metallopeptidase 24 | 4 | 2 | ||||||||
MIRT005387 | Mmp24 | matrix metallopeptidase 24 | 2 | 1 | ||||||||
MIRT005486 | GRN | granulin precursor | 4 | 1 | ||||||||
MIRT005522 | FGG | fibrinogen gamma chain | 2 | 1 | ||||||||
MIRT005533 | FGA | fibrinogen alpha chain | 2 | 1 | ||||||||
MIRT005534 | FGB | fibrinogen beta chain | 2 | 1 | ||||||||
MIRT005567 | COL3A1 | collagen type III alpha 1 chain | 5 | 4 | ||||||||
MIRT005568 | COL4A1 | collagen type IV alpha 1 chain | 7 | 9 | ||||||||
MIRT005570 | MMP2 | matrix metallopeptidase 2 | 5 | 8 | ||||||||
MIRT005614 | BBC3 | BCL2 binding component 3 | 2 | 2 | ||||||||
MIRT005667 | ADAM12 | ADAM metallopeptidase domain 12 | 5 | 3 | ||||||||
MIRT005669 | NID1 | nidogen 1 | 4 | 1 | ||||||||
MIRT006054 | HMGA2 | high mobility group AT-hook 2 | 3 | 1 | ||||||||
MIRT006058 | TGFB2 | transforming growth factor beta 2 | 3 | 2 | ||||||||
MIRT006059 | TGFB1 | transforming growth factor beta 1 | 2 | 1 | ||||||||
MIRT006060 | BMP1 | bone morphogenetic protein 1 | 3 | 2 | ||||||||
MIRT006098 | PTEN | phosphatase and tensin homolog | 7 | 3 | ||||||||
MIRT006251 | NASP | nuclear autoantigenic sperm protein | 2 | 1 | ||||||||
MIRT006486 | PPP1R13B | protein phosphatase 1 regulatory subunit 13B | 2 | 1 | ||||||||
MIRT006488 | CDC42 | cell division cycle 42 | 4 | 2 | ||||||||
MIRT006753 | GSK3B | glycogen synthase kinase 3 beta | 1 | 1 | ||||||||
MIRT006815 | PIK3CG | phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma | 3 | 1 | ||||||||
MIRT006915 | NKIRAS2 | NFKB inhibitor interacting Ras like 2 | 5 | 3 | ||||||||
MIRT007011 | RAX | retina and anterior neural fold homeobox | 2 | 1 | ||||||||
MIRT007033 | TBX21 | T-box 21 | 1 | 1 | ||||||||
MIRT007034 | IFNG | interferon gamma | 1 | 1 | ||||||||
MIRT007102 | DUSP2 | dual specificity phosphatase 2 | 3 | 3 | ||||||||
MIRT007254 | FOS | Fos proto-oncogene, AP-1 transcription factor subunit | 3 | 3 | ||||||||
MIRT027237 | PIK3R1 | phosphoinositide-3-kinase regulatory subunit 1 | 2 | 2 | ||||||||
MIRT027238 | IMPDH1 | inosine monophosphate dehydrogenase 1 | 2 | 2 | ||||||||
MIRT027239 | MYCN | MYCN proto-oncogene, bHLH transcription factor | 3 | 3 | ||||||||
MIRT048359 | SCAF8 | SR-related CTD associated factor 8 | 1 | 1 | ||||||||
MIRT048360 | CLDN1 | claudin 1 | 1 | 1 | ||||||||
MIRT048361 | MRPS35 | mitochondrial ribosomal protein S35 | 1 | 1 | ||||||||
MIRT048362 | RSL24D1 | ribosomal L24 domain containing 1 | 1 | 1 | ||||||||
MIRT048363 | LRP10 | LDL receptor related protein 10 | 1 | 1 | ||||||||
MIRT048364 | HP1BP3 | heterochromatin protein 1 binding protein 3 | 1 | 1 | ||||||||
MIRT048365 | B4GALT5 | beta-1,4-galactosyltransferase 5 | 1 | 1 | ||||||||
MIRT048366 | KIAA1671 | KIAA1671 | 1 | 1 | ||||||||
MIRT048367 | NNT | nicotinamide nucleotide transhydrogenase | 1 | 1 | ||||||||
MIRT048368 | IFIH1 | interferon induced with helicase C domain 1 | 1 | 1 | ||||||||
MIRT048369 | TPT1 | tumor protein, translationally-controlled 1 | 1 | 1 | ||||||||
MIRT048370 | RUNDC3B | RUN domain containing 3B | 1 | 1 | ||||||||
MIRT048371 | CECR2 | CECR2, histone acetyl-lysine reader | 1 | 1 | ||||||||
MIRT048372 | TPD52L2 | tumor protein D52 like 2 | 1 | 1 | ||||||||
MIRT048373 | NUS1 | NUS1 dehydrodolichyl diphosphate synthase subunit | 1 | 1 | ||||||||
MIRT048374 | CIT | citron rho-interacting serine/threonine kinase | 1 | 1 | ||||||||
MIRT048375 | GNB2L1 | receptor for activated C kinase 1 | 1 | 1 | ||||||||
MIRT048376 | SMARCC1 | SWI/SNF related, matrix associated, actin dependent regulator of chromatin subfamily c member 1 | 1 | 1 | ||||||||
MIRT048377 | PRKAA1 | protein kinase AMP-activated catalytic subunit alpha 1 | 1 | 1 | ||||||||
MIRT048378 | PIGN | phosphatidylinositol glycan anchor biosynthesis class N | 1 | 1 | ||||||||
MIRT048379 | RPS4X | ribosomal protein S4, X-linked | 1 | 1 | ||||||||
MIRT048380 | CCSAP | centriole, cilia and spindle associated protein | 1 | 1 | ||||||||
MIRT048381 | CALU | calumenin | 1 | 1 | ||||||||
MIRT048382 | NREP | neuronal regeneration related protein | 1 | 1 | ||||||||
MIRT048383 | MKI67 | marker of proliferation Ki-67 | 1 | 1 | ||||||||
MIRT053293 | TDG | thymine DNA glycosylase | 5 | 5 | ||||||||
MIRT053581 | CCND2 | cyclin D2 | 5 | 3 | ||||||||
MIRT053738 | COL4A5 | collagen type IV alpha 5 chain | 1 | 1 | ||||||||
MIRT053739 | COL7A1 | collagen type VII alpha 1 chain | 1 | 1 | ||||||||
MIRT053740 | COL15A1 | collagen type XV alpha 1 chain | 1 | 1 | ||||||||
MIRT053741 | COL2A1 | collagen type II alpha 1 chain | 1 | 1 | ||||||||
MIRT053742 | COL4A6 | collagen type IV alpha 6 chain | 1 | 1 | ||||||||
MIRT053743 | CSGALNACT2 | chondroitin sulfate N-acetylgalactosaminyltransferase 2 | 1 | 1 | ||||||||
MIRT053744 | SOX12 | SRY-box 12 | 1 | 1 | ||||||||
MIRT053745 | MAP2K6 | mitogen-activated protein kinase kinase 6 | 1 | 1 | ||||||||
MIRT053746 | TGIF2 | TGFB induced factor homeobox 2 | 1 | 1 | ||||||||
MIRT053747 | SERPINH1 | serpin family H member 1 | 2 | 2 | ||||||||
MIRT053748 | NOTCH2 | notch 2 | 4 | 1 | ||||||||
MIRT053749 | PPARD | peroxisome proliferator activated receptor delta | 1 | 1 | ||||||||
MIRT054045 | SNAI3 | snail family transcriptional repressor 3 | 2 | 1 | ||||||||
MIRT054192 | AKT2 | AKT serine/threonine kinase 2 | 4 | 2 | ||||||||
MIRT054574 | PER1 | period circadian clock 1 | 3 | 1 | ||||||||
MIRT060983 | LAMC1 | laminin subunit gamma 1 | 3 | 1 | ||||||||
MIRT061662 | BTG2 | BTG anti-proliferation factor 2 | 2 | 4 | ||||||||
MIRT067385 | TMTC3 | transmembrane and tetratricopeptide repeat containing 3 | 2 | 4 | ||||||||
MIRT079942 | RNF138 | ring finger protein 138 | 2 | 2 | ||||||||
MIRT080798 | SH3GLB1 | SH3 domain containing GRB2 like, endophilin B1 | 2 | 4 | ||||||||
MIRT081893 | KCTD15 | potassium channel tetramerization domain containing 15 | 2 | 8 | ||||||||
MIRT082515 | CALM3 | calmodulin 3 | 2 | 2 | ||||||||
MIRT085293 | CCNT2 | cyclin T2 | 2 | 6 | ||||||||
MIRT102856 | INSIG1 | insulin induced gene 1 | 2 | 2 | ||||||||
MIRT207249 | TET3 | tet methylcytosine dioxygenase 3 | 2 | 2 | ||||||||
MIRT207755 | VHL | von Hippel-Lindau tumor suppressor | 2 | 4 | ||||||||
MIRT210969 | TET2 | tet methylcytosine dioxygenase 2 | 1 | 1 | ||||||||
MIRT211650 | ABCE1 | ATP binding cassette subfamily E member 1 | 2 | 2 | ||||||||
MIRT213230 | REST | RE1 silencing transcription factor | 2 | 10 | ||||||||
MIRT225103 | GOLGA7 | golgin A7 | 2 | 2 | ||||||||
MIRT250481 | MAZ | MYC associated zinc finger protein | 2 | 2 | ||||||||
MIRT264266 | FAM102B | family with sequence similarity 102 member B | 2 | 2 | ||||||||
MIRT267090 | ZFP91 | ZFP91 zinc finger protein | 2 | 2 | ||||||||
MIRT303363 | MXD1 | MAX dimerization protein 1 | 2 | 1 | ||||||||
MIRT316344 | ULBP2 | UL16 binding protein 2 | 2 | 2 | ||||||||
MIRT401476 | AIM1 | crystallin beta-gamma domain containing 1 | 2 | 1 | ||||||||
MIRT437369 | LAMC2 | laminin subunit gamma 2 | 3 | 1 | ||||||||
MIRT437372 | ITGA6 | integrin subunit alpha 6 | 3 | 2 | ||||||||
MIRT437552 | COL5A2 | collagen type V alpha 2 chain | 1 | 1 | ||||||||
MIRT437553 | COL10A1 | collagen type X alpha 1 chain | 1 | 1 | ||||||||
MIRT437554 | SPARC | secreted protein acidic and cysteine rich | 1 | 1 | ||||||||
MIRT437555 | FBN1 | fibrillin 1 | 1 | 1 | ||||||||
MIRT437556 | LOX | lysyl oxidase | 2 | 2 | ||||||||
MIRT437557 | PDGFRB | platelet derived growth factor receptor beta | 2 | 2 | ||||||||
MIRT437710 | PHACTR2 | phosphatase and actin regulator 2 | 2 | 1 | ||||||||
MIRT437713 | TUBB2A | tubulin beta 2A class IIa | 2 | 1 | ||||||||
MIRT437716 | EMP1 | epithelial membrane protein 1 | 2 | 1 | ||||||||
MIRT437719 | SNX24 | sorting nexin 24 | 2 | 1 | ||||||||
MIRT437722 | AMFR | autocrine motility factor receptor | 2 | 1 | ||||||||
MIRT437725 | RIOK3 | RIO kinase 3 | 2 | 1 | ||||||||
MIRT437728 | WDR26 | WD repeat domain 26 | 4 | 3 | ||||||||
MIRT437731 | DSC2 | desmocollin 2 | 2 | 1 | ||||||||
MIRT437870 | IL32 | interleukin 32 | 1 | 1 | ||||||||
MIRT438911 | GATA3 | GATA binding protein 3 | 2 | 1 | ||||||||
MIRT438912 | PDGFRA | platelet derived growth factor receptor alpha | 2 | 1 | ||||||||
MIRT438913 | PDGFC | platelet derived growth factor C | 2 | 1 | ||||||||
MIRT438914 | PDGFB | platelet derived growth factor subunit B | 2 | 1 | ||||||||
MIRT438915 | PDGFA | platelet derived growth factor subunit A | 2 | 1 | ||||||||
MIRT438916 | MMP9 | matrix metallopeptidase 9 | 2 | 1 | ||||||||
MIRT438917 | LOXL4 | lysyl oxidase like 4 | 2 | 1 | ||||||||
MIRT438918 | LOXL2 | lysyl oxidase like 2 | 2 | 1 | ||||||||
MIRT438919 | ITGB1 | integrin subunit beta 1 | 2 | 1 | ||||||||
MIRT438920 | ANGPTL4 | angiopoietin like 4 | 2 | 1 | ||||||||
MIRT454812 | NEDD9 | neural precursor cell expressed, developmentally down-regulated 9 | 2 | 2 | ||||||||
MIRT456827 | MORF4L2 | mortality factor 4 like 2 | 2 | 8 | ||||||||
MIRT462151 | RPL22 | ribosomal protein L22 | 2 | 2 | ||||||||
MIRT465314 | TRAM2 | translocation associated membrane protein 2 | 2 | 2 | ||||||||
MIRT467808 | SLC2A14 | solute carrier family 2 member 14 | 2 | 2 | ||||||||
MIRT467829 | SLC29A2 | solute carrier family 29 member 2 | 2 | 2 | ||||||||
MIRT467971 | SLC16A1 | solute carrier family 16 member 1 | 2 | 4 | ||||||||
MIRT468225 | SGK1 | serum/glucocorticoid regulated kinase 1 | 2 | 2 | ||||||||
MIRT469448 | REL | REL proto-oncogene, NF-kB subunit | 2 | 2 | ||||||||
MIRT469723 | RAB40C | RAB40C, member RAS oncogene family | 2 | 2 | ||||||||
MIRT469841 | R3HDM4 | R3H domain containing 4 | 2 | 2 | ||||||||
MIRT472643 | NAA40 | N(alpha)-acetyltransferase 40, NatD catalytic subunit | 2 | 2 | ||||||||
MIRT474209 | LEPRE1 | prolyl 3-hydroxylase 1 | 1 | 1 | ||||||||
MIRT474576 | KLHDC3 | kelch domain containing 3 | 2 | 2 | ||||||||
MIRT475837 | HDGF | heparin binding growth factor | 2 | 4 | ||||||||
MIRT476721 | FRK | fyn related Src family tyrosine kinase | 2 | 4 | ||||||||
MIRT477473 | ELMSAN1 | ELM2 and Myb/SANT domain containing 1 | 2 | 2 | ||||||||
MIRT478668 | CTC1 | CST telomere replication complex component 1 | 2 | 14 | ||||||||
MIRT478710 | CSRNP2 | cysteine and serine rich nuclear protein 2 | 2 | 2 | ||||||||
MIRT478985 | COMMD2 | COMM domain containing 2 | 2 | 2 | ||||||||
MIRT479826 | CCNA2 | cyclin A2 | 2 | 8 | ||||||||
MIRT479901 | CCDC117 | coiled-coil domain containing 117 | 2 | 2 | ||||||||
MIRT480066 | CAND1 | cullin associated and neddylation dissociated 1 | 2 | 2 | ||||||||
MIRT482012 | AMER1 | APC membrane recruitment protein 1 | 2 | 8 | ||||||||
MIRT489024 | C1QTNF6 | C1q and TNF related 6 | 5 | 2 | ||||||||
MIRT492513 | RAET1L | retinoic acid early transcript 1L | 2 | 2 | ||||||||
MIRT493825 | FSCN1 | fascin actin-bundling protein 1 | 2 | 2 | ||||||||
MIRT495936 | SLC7A5P2 | solute carrier family 7 member 5 pseudogene 2 | 2 | 2 | ||||||||
MIRT496358 | PPY | pancreatic polypeptide | 2 | 2 | ||||||||
MIRT496662 | TMEM237 | transmembrane protein 237 | 2 | 2 | ||||||||
MIRT497644 | GLDN | gliomedin | 2 | 2 | ||||||||
MIRT501878 | MORF4L1 | mortality factor 4 like 1 | 2 | 8 | ||||||||
MIRT502932 | CDC42SE1 | CDC42 small effector 1 | 2 | 4 | ||||||||
MIRT506750 | LDOC1L | retrotransposon Gag like 6 | 2 | 6 | ||||||||
MIRT507168 | GAS2L3 | growth arrest specific 2 like 3 | 2 | 2 | ||||||||
MIRT514918 | MDM2 | MDM2 proto-oncogene | 2 | 6 | ||||||||
MIRT523962 | DYNLT1 | dynein light chain Tctex-type 1 | 2 | 4 | ||||||||
MIRT527675 | CASP8 | caspase 8 | 2 | 2 | ||||||||
MIRT536936 | HECW1 | HECT, C2 and WW domain containing E3 ubiquitin protein ligase 1 | 2 | 2 | ||||||||
MIRT537359 | FJX1 | four jointed box 1 | 2 | 2 | ||||||||
MIRT537687 | ENPP2 | ectonucleotide pyrophosphatase/phosphodiesterase 2 | 2 | 2 | ||||||||
MIRT538124 | DDX6 | DEAD-box helicase 6 | 2 | 2 | ||||||||
MIRT538813 | C21orf91 | chromosome 21 open reading frame 91 | 2 | 2 | ||||||||
MIRT546938 | PTP4A1 | protein tyrosine phosphatase type IVA, member 1 | 2 | 2 | ||||||||
MIRT547104 | PLAG1 | PLAG1 zinc finger | 2 | 2 | ||||||||
MIRT547823 | ISG20L2 | interferon stimulated exonuclease gene 20 like 2 | 2 | 2 | ||||||||
MIRT548237 | FEM1B | fem-1 homolog B | 2 | 2 | ||||||||
MIRT550036 | WWTR1 | WW domain containing transcription regulator 1 | 2 | 2 | ||||||||
MIRT552619 | ZBTB5 | zinc finger and BTB domain containing 5 | 2 | 2 | ||||||||
MIRT556562 | LIMS1 | LIM zinc finger domain containing 1 | 2 | 2 | ||||||||
MIRT558857 | CDC23 | cell division cycle 23 | 2 | 2 | ||||||||
MIRT565485 | SPRTN | SprT-like N-terminal domain | 2 | 2 | ||||||||
MIRT568205 | CBX6 | chromobox 6 | 2 | 2 | ||||||||
MIRT576774 | Tmem127 | transmembrane protein 127 | 2 | 2 | ||||||||
MIRT576958 | Pigs | phosphatidylinositol glycan anchor biosynthesis, class S | 2 | 3 | ||||||||
MIRT610003 | PIGS | phosphatidylinositol glycan anchor biosynthesis class S | 2 | 3 | ||||||||
MIRT616511 | COX7A2L | cytochrome c oxidase subunit 7A2 like | 2 | 2 | ||||||||
MIRT640887 | ENTPD1 | ectonucleoside triphosphate diphosphohydrolase 1 | 2 | 2 | ||||||||
MIRT641350 | RAB11FIP1 | RAB11 family interacting protein 1 | 2 | 2 | ||||||||
MIRT642978 | TESPA1 | thymocyte expressed, positive selection associated 1 | 2 | 2 | ||||||||
MIRT643634 | YY2 | YY2 transcription factor | 2 | 2 | ||||||||
MIRT644386 | ZNF286A | zinc finger protein 286A | 2 | 2 | ||||||||
MIRT650749 | YAE1D1 | Yae1 domain containing 1 | 2 | 2 | ||||||||
MIRT661585 | EPHX2 | epoxide hydrolase 2 | 2 | 2 | ||||||||
MIRT664287 | RNMTL1 | mitochondrial rRNA methyltransferase 3 | 2 | 2 | ||||||||
MIRT689393 | ZNF850 | zinc finger protein 850 | 2 | 2 | ||||||||
MIRT693815 | SEC31A | SEC31 homolog A, COPII coat complex component | 2 | 2 | ||||||||
MIRT694532 | TRIM72 | tripartite motif containing 72 | 2 | 2 | ||||||||
MIRT694628 | ZFPM1 | zinc finger protein, FOG family member 1 | 2 | 2 | ||||||||
MIRT695135 | PRY2 | PTPN13-like, Y-linked 2 | 2 | 2 | ||||||||
MIRT695152 | PRY | PTPN13-like, Y-linked | 2 | 2 | ||||||||
MIRT703640 | FBRS | fibrosin | 2 | 2 | ||||||||
MIRT704551 | CNBP | CCHC-type zinc finger nucleic acid binding protein | 2 | 2 | ||||||||
MIRT704967 | CBX2 | chromobox 2 | 2 | 2 | ||||||||
MIRT705497 | ASXL2 | additional sex combs like 2, transcriptional regulator | 2 | 2 | ||||||||
MIRT707993 | OTUD4 | OTU deubiquitinase 4 | 2 | 2 | ||||||||
MIRT708741 | FAM71F2 | family with sequence similarity 71 member F2 | 2 | 2 | ||||||||
MIRT710621 | COLEC10 | collectin subfamily member 10 | 2 | 2 | ||||||||
MIRT713056 | IFRD1 | interferon related developmental regulator 1 | 2 | 2 | ||||||||
MIRT715515 | MAPKBP1 | mitogen-activated protein kinase binding protein 1 | 2 | 2 | ||||||||
MIRT720770 | FAM193A | family with sequence similarity 193 member A | 2 | 2 | ||||||||
MIRT731925 | AQP4 | aquaporin 4 | 3 | 1 | ||||||||
MIRT732673 | HMGB1 | high mobility group box 1 | 3 | 0 | ||||||||
MIRT734350 | IL6 | interleukin 6 | 1 | 0 | ||||||||
MIRT734351 | TP53 | tumor protein p53 | 1 | 0 | ||||||||
MIRT734565 | BCL2L11 | BCL2 like 11 | 2 | 0 | ||||||||
MIRT734770 | TRIM44 | tripartite motif containing 44 | 2 | 0 | ||||||||
MIRT734771 | CCNE1 | cyclin E1 | 2 | 0 | ||||||||
MIRT735260 | STAT3 | signal transducer and activator of transcription 3 | 6 | 1 | ||||||||
MIRT735414 | HBP1 | HMG-box transcription factor 1 | 3 | 0 | ||||||||
MIRT735537 | HIF3A | hypoxia inducible factor 3 alpha subunit | 3 | 0 | ||||||||
MIRT735639 | HUWE1 | HECT, UBA and WWE domain containing 1, E3 ubiquitin protein ligase | 3 | 0 | ||||||||
MIRT735641 | AKT3 | AKT serine/threonine kinase 3 | 3 | 0 | ||||||||
MIRT735943 | DNM3OS | DNM3 opposite strand/antisense RNA | 4 | 0 | ||||||||
MIRT737493 | SMAD3 | SMAD family member 3 | 1 | 0 | ||||||||
MIRT737577 | SNAI1 | snail family transcriptional repressor 1 | 2 | 0 | ||||||||
MIRT755941 | SLMAP | sarcolemma associated protein | 4 | 1 | ||||||||
MIRT755963 | ROBO1 | roundabout guidance receptor 1 | 5 | 1 | ||||||||
MIRT755964 | SRGAP2 | SLIT-ROBO Rho GTPase activating protein 2 | 5 | 1 | ||||||||
MIRT756271 | YWHAE | tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein epsilon | 3 | 1 | ||||||||
MIRT756364 | LIN7A | lin-7 homolog A, crumbs cell polarity complex component | 2 | 1 | ||||||||
MIRT756474 | COL5A1 | collagen type V alpha 1 chain | 3 | 1 |
miRNA-Drug Associations | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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miRNA-Drug Resistance Associations | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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