Accession ID: MIRT004248 [miRNA, hsa-miR-203a :: TP63, target gene]
pre-miRNA Information
pre-miRNA ID hsa-mir-203aLinkOut: [miRBase ]
Description Homo sapiens miR-203a stem-loop
Comment This human miRNA was predicted by computational methods using conservation with mouse and Fugu rubripes sequences .
2nd Structure of pre-miRNA
Mature miRNA Information
Mature miRNA hsa-miR-203a-3p
Mature Sequence 65| GUGAAAUGUUUAGGACCACUAG |86
Evidence Experimental
Experiments Cloned
Putative hsa-miR-203a-3p Targets LinkOut: [ TargetScanS 5.1 | MicroCosm | microRNA.org | miRecords | miRDB | miRo | miRNAMap 2.0 ]
Gene Information
Gene Symbol TP63 LinkOut: [ Entrez Gene | BioGPS | Wikipedia | iHop ]
Synonyms AIS, B(p51A), B(p51B), EEC3, KET, LMS, NBP, OFC8, RHS, SHFM4, TP53CP, TP53L, TP73L, p40, p51, p53CP, p63, p73H, p73L
Description tumor protein p63
Transcript NM_0011149    LinkOut: [ RefSeq ]
Other Transcripts NM_0011149 , NM_0011149 , NM_0011149 , NM_0011149 , NM_0037   
Expression LinkOut: [ BioGPS ]
Putative miRNA Targets on TP63 LinkOut: [ TargetScan 5.1 | MicroCosm | miRNAMap 2.0 ]
3'UTR of TP63
(miRNA target sites are highlighted)
>TP63|NM_0011149|3'UTR
   1 AAATCCCTGAGCAATTTCGACATGCGATCTGGAAGGGCATCCTGGACCACCGGCAGCTCCACGAATTCTCCTCCCCTTCT
  81 CATCTCCTGCGGACCCCAAGCAGTGCCTCTACAGTCAGTGTGGGCTCCAGTGAGACCCGGGGTGAGCGTGTTATTGATGC
 161 TGTGCGATTCACCCTCCGCCAGACCATCTCTTTCCCACCCCGAGATGAGTGGAATGACTTCAACTTTGACATGGATGCTC
 241 GCCGCAATAAGCAACAGCGCATCAAAGAGGAGGGGGAGTGAGCCTCACCATGTGAGCTCTTCCTATCCCTCTCCTAACTG
 321 CCAGCCCCCTAAAAGCACTCCTGCTTAATCTTCAAAGCCTTCTCCCTAGCTCCTCCCCTTCCTCTTGTCTGATTTCTTAG
 401 GGGAAGGAGAAGTAAGAGGCTACCTCTTACCTAACATCTGACCTGGCATCTAATTCTGATTCTGGCTTTAAGCCTTCAAA
 481 ACTATAGCTTGCAGAACTGTAGCTGCCATGGCTAGGTAGAAGTGAGCAAAAAAGAGTTGGGTGTCTCCTTAAGCTGCAGA
 561 GATTTCTCATTGACTTTTATAAAGCATGTTCACCCTTATAGTCTAAGACTATATATATAAATGTATAAATATACAGTATA
 641 GATTTTTGGGTGGGGGGCATTGAGTATTGTTTAAAATGTAATTTAAATGAAAGAAAATTGAGTTGCACTTATTGACCATT
 721 TTTTAATTTACTTGTTTTGGATGGCTTGTCTATACTCCTTCCCTTAAGGGGTATCATGTATGGTGATAGGTATCTAGAGC
 801 TTAATGCTACATGTGAGTGACGATGATGTACAGATTCTTTCAGTTCTTTGGATTCTAAATACATGCCACATCAAACCTTT
 881 GAGTAGATCCATTTCCATTGCTTATTATGTAGGTAAGACTGTAGATATGTATTCTTTTCTCAGTGTTGGTATATTTTATA
 961 TTACTGACATTTCTTCTAGTGATGATGGTTCACGTTGGGGTGATTTAATCCAGTTATAAGAAGAAGTTCATGTCCAAACG
1041 TCCTCTTTAGTTTTTGGTTGGGAATGAGGAAAATTCTTAAAAGGCCCATAGCAGCCAGTTCAAAAACACCCGACGTCATG
1121 TATTTGAGCATATCAGTAACCCCCTTAAATTTAATACCAGATACCTTATCTTACAATATTGATTGGGAAAACATTTGCTG
1201 CCATTACAGAGGTATTAAAACTAAATTTCACTACTAGATTGACTAACTCAAATACACATTTGCTACTGTTGTAAGAATTC
1281 TGATTGATTTGATTGGGATGAATGCCATCTATCTAGTTCTAACAGTGAAGTTTTACTGTCTATTAATATTCAGGGTAAAT
1361 AGGAATCATTCAGAAATGTTGAGTCTGTACTAAACAGTAAGATATCTCAATGAACCATAAATTCAACTTTGTAAAAATCT
1441 TTTGAAGCATAGATAATATTGTTTGGTAAATGTTTCTTTTGTTTGGTAAATGTTTCTTTTAAAGACCCTCCTATTCTATA
1521 AAACTCTGCATGTAGAGGCTTGTTTACCTTTCTCTCTCTAAGGTTTACAATAGGAGTGGTGATTTGAAAAATATAAAATT
1601 ATGAGATTGGTTTTCCTGTGGCATAAATTGCATCACTGTATCATTTTCTTTTTTAACCGGTAAGAGTTTCAGTTTGTTGG
1681 AAAGTAACTGTGAGAACCCAGTTTCCCGTCCATCTCCCTTAGGGACTACCCATAGACATGAAAGGTCCCCACAGAGCAAG
1761 AGATAAGTCTTTCATGGCTGCTGTTGCTTAAACCACTTAAACGAAGAGTTCCCTTGAAACTTTGGGAAAACATGTTAATG
1841 ACAATATTCCAGATCTTTCAGAAATATAACACATTTTTTTGCATGCATGCAAATGAGCTCTGAAATCTTCCCATGCATTC
1921 TGGTCAAGGGCTGTCATTGCACATAAGCTTCCATTTTAATTTTAAAGTGCAAAAGGGCCAGCGTGGCTCTAAAAGGTAAT
2001 GTGTGGATTGCCTCTGAAAAGTGTGTATATATTTTGTGTGAAATTGCATACTTTGTATTTTGATTATTTTTTTTTTCTTC
2081 TTGGGATAGTGGGATTTCCAGAACCACACTTGAAACCTTTTTTTATCGTTTTTGTATTTTCATGAAAATACCATTTAGTA
2161 AGAATACCACATCAAATAAGAAATAATGCTACAATTTTAAGAGGGGAGGGAAGGGAAAGTTTTTTTTTATTATTTTTTTA
2241 AAATTTTGTATGTTAAAGAGAATGAGTCCTTGATTTCAAAGTTTTGTTGTACTTAAATGGTAATAAGCACTGTAAACTTC
2321 TGCAACAAGCATGCAGCTTTGCAAACCCATTAAGGGGAAGAATGAAAGCTGTTCCTTGGTCCTAGTAAGAAGACAAACTG
2401 CTTCCCTTACTTTGCTGAGGGTTTGAATAAACCTAGGACTTCCGAGCTATGTCAGTACTATTCAGGTAACACTAGGGCCT
2481 TGGAAATTCCTGTACTGTGTCTCATGGATTTGGCACTAGCCAAAGCGAGGCACCCTTACTGGCTTACCTCCTCATGGCAG
2561 CCTACTCTCCTTGAGTGTATGAGTAGCCAGGGTAAGGGGTAAAAGGATAGTAAGCATAGAAACCACTAGAAAGTGGGCTT
2641 AATGGAGTTCTTGTGGCCTCAGCTCAATGCAGTTAGCTGAAGAATTGAAAAGTTTTTGTTTGGAGACGTTTATAAACAGA
2721 AATGGAAAGCAGAGTTTTCATTAAATCCTTTTACCTTTTTTTTTTCTTGGTAATCCCCTAAAATAACAGTATGTGGGATA
2801 TTGAATGTTAAAGGGATATTTTTTTCTATTATTTTTATAATTGTACAAAATTAAGCAAATGTTAAAAGTTTTATATGCTT
2881 TATTAATGTTTTCAAAAGGTATTATACATGTGATACATTTTTTAAGCTTCAGTTGCTTGTCTTCTGGTACTTTCTGTTAT
2961 GGGCTTTTGGGGAGCCAGAAGCCAATCTACAATCTCTTTTTGTTTGCCAGGACATGCAATAAAATTTAAAAAATAAATAA
3041 AAACTAATTAAGAAATTG
Target sites Provided by authors  Predicted by miRanda
miRNA-target interactions (Predicted by miRanda)
IDDuplex structurePositionScoreMFE
1
miRNA  3' gaUCACCAGGAUU----UGUAAAGUg 5'
            || ||| :|||    | |||||| 
Target 5' acAGAGGTATTAAAACTAAATTTCAc 3'
1206 - 1231 134.00 -12.00
2
miRNA  3' gaUCAC-CAGGAUUUGUAAAGUg 5'
            | || ||||| :  |||||| 
Target 5' agAATGAGTCCTTG--ATTTCAa 3'
2259 - 2279 131.00 -10.80
3
miRNA  3' gaucaccAGGAUUUGUAAAGug 5'
                 | || :|||||||  
Target 5' tttatatTACT-GACATTTCtt 3'
955 - 975 130.00 -6.70
Experimental Support 1 for Functional miRNA-Target Interaction
miRNA:Target hsa-miR-203a :: TP63    [ Functional MTI ]
Validation Method Luciferase reporter assay ,
Conditions Not mention
Location of target site 3'UTR
Original Description (Extracted from the article) ... these results indicate that miR-203’s effect on p63 is direct and is mediated through these 3'UTR target sites. ...

- Yi, R. Poy, M. N. Stoffel, M. Fuchs, E., 2008, Nature.

Article - Yi, R. Poy, M. N. Stoffel, M. Fuchs, E.
- Nature, 2008
In stratified epithelial tissues, homeostasis relies on the self-renewing capacity of stem cells located within the innermost basal layer. As basal cells become suprabasal, they lose proliferative potential and embark on a terminal differentiation programme. Here, we show that microRNA-203 is induced in the skin concomitantly with stratification and differentiation. By altering miR-203's spatiotemporal expression in vivo, we show that miR-203 promotes epidermal differentiation by restricting proliferative potential and inducing cell-cycle exit. We identify p63 as one of the conserved targets of miR-203 across vertebrates. Notably, p63 is an essential regulator of stem-cell maintenance in stratified epithelial tissues. We show that miR-203 directly represses the expression of p63: it fails to switch off suprabasally when either Dicer1 or miR-203 is absent and it becomes repressed basally when miR-203 is prematurely expressed. Our findings suggest that miR-203 defines a molecular boundary between proliferative basal progenitors and terminally differentiating suprabasal cells, ensuring proper identity of neighbouring layers.
LinkOut: [PMID: 18311128]
Experimental Support 2 for Functional miRNA-Target Interaction
miRNA:Target hsa-miR-203a :: TP63    [ Functional MTI ]
Validation Method qRT-PCR , Western blot , Luciferase reporter assay , Other
Conditions HEK293E
Location of target site 3'UTR
Tools used in this research TargetScan
Original Description (Extracted from the article) ... Together, the data presented here indicate that miR-203, by targeting ΔNp63 mRNA, acts as a switch between keratinocyte proliferation and differentiation in adult epidermis. ...

- Lena, A. M. Shalom-Feuerstein, R. Rivetti et al., 2008, Cell Death Differ.

Article - Lena, A. M. Shalom-Feuerstein, R. Rivetti et al.
- Cell Death Differ, 2008
The epidermis, the outer layer of the skin composed of keratinocytes, is a stratified epithelium that functions as a barrier to protect the organism from dehydration and external insults. The epidermis develops depending on the transcription factor p63, a member of the p53 family of transcription factors. p63 is strongly expressed in the innermost basal layer where epithelial cells with high clonogenic and proliferative capacity reside. Deletion of p63 in mice results in a dramatic loss of all keratinocytes and loss of stratified epithelia, probably due to a premature proliferative rundown of the stem and transient amplifying cells. Here we report that microRNA (miR)-203 is induced in vitro in primary keratinocytes in parallel with differentiation. We found that miR-203 specifically targets human and mouse p63 3'-UTRs and not SOCS-3, despite bioinformatics alignment between miR-203 and SOCS-3 3'-UTR. We also show that miR-203 overexpression in proliferating keratinocytes is not sufficient to induce full epidermal differentiation in vitro. In addition, we demonstrate that miR-203 is downregulated during the epithelial commitment of embryonic stem cells, and that overexpression of miR-203 in rapidly proliferating human primary keratinocytes significantly reduces their clonogenic capacity. The results suggest that miR-203, by regulating the DeltaNp63 expression level, is a key molecule controlling the p63-dependent proliferative potential of epithelial precursor cells both during keratinocyte differentiation and in epithelial development. In addition, we have shown that miR-203 can regulate DeltaNp63 levels upon genotoxic damage in head and neck squamous cell carcinoma cells, thus controlling cell survival.
LinkOut: [PMID: 18483491]
MiRNA-Target Expression Profile:

 
MiRNA-Target Interaction Network:
Strong evidence (reporter assay, western blot, qRT-PCR or qPCR)
Other evidence
32 hsa-miR-203a Target Genes:
ID Target Description Validation methods
Strong evidence Less strong evidence
MIRT000947 UVRAG UV radiation resistance associated gene 1 1
MIRT003032 ABL1 c-abl oncogene 1, non-receptor tyrosine kinase 2 2
MIRT004248 TP63 tumor protein p63 4 2
MIRT004713 ABCE1 ATP-binding cassette, sub-family E (OABP), member 1 4 1
MIRT004723 CDK6 cyclin-dependent kinase 6 4 1
MIRT005062 SOCS3 suppressor of cytokine signaling 3 5 3
MIRT005453 BCL2L2 BCL2-like 2 4 1
MIRT005684 PPM1D protein phosphatase, Mg2+/Mn2+ dependent, 1D 1 1
MIRT005747 GDAP1 ganglioside induced differentiation associated protein 1 2 1
MIRT005749 EDNRA endothelin receptor type A 3 1
MIRT005750 EYA4 eyes absent homolog 4 (Drosophila) 3 1
MIRT006035 ZEB2 zinc finger E-box binding homeobox 2 3 1
MIRT006036 BMI1 BMI1 polycomb ring finger oncogene 4 2
MIRT006037 RUNX2 runt-related transcription factor 2 3 1
MIRT006038 SMAD4 SMAD family member 4 3 1
MIRT006039 E2F1 E2F transcription factor 1 3 1
MIRT006040 MMP10 matrix metallopeptidase 10 (stromelysin 2) 3 1
MIRT006041 DLX5 distal-less homeobox 5 3 1
MIRT006061 IL6 interleukin 6 (interferon, beta 2) 1 1
MIRT006062 MMP1 matrix metallopeptidase 1 (interstitial collagenase) 1 1
MIRT006104 AKT2 v-akt murine thymoma viral oncogene homolog 2 2 1
MIRT006256 BIRC5 baculoviral IAP repeat containing 5 2 2
MIRT006268 E2F3 E2F transcription factor 3 1 1
MIRT006269 ZNF148 zinc finger protein 148 1 1
MIRT006496 CREB1 cAMP responsive element binding protein 1 2 1
MIRT006684 TJP2 tight junction protein 2 2 1
MIRT006856 SOCS6 suppressor of cytokine signaling 6 1 1
MIRT006857 TNF tumor necrosis factor 1 1
MIRT006858 IL24 interleukin 24 1 1
MIRT007227 SNAI2 snail homolog 2 (Drosophila) 1 1
MIRT007353 CBLL1 Cbl proto-oncogene, E3 ubiquitin protein ligase-like 1 2 1
MIRT007368 MYD88 myeloid differentiation primary response gene (88) 3 1