Accession ID: MIRT004904 [miRNA, hsa-miR-145-5p :: POU5F1, target gene]
pre-miRNA Information
pre-miRNA ID hsa-mir-145LinkOut: [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
Disease
Mature miRNA Information
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 Information
Gene Symbol POU5F1 LinkOut: [ Entrez Gene | BioGPS | Wikipedia | iHop ]
Synonyms MGC22487, OCT3, OCT4, OTF-3, OTF3, OTF4, Oct-3, Oct-4
Description POU class 5 homeobox 1
Transcript NM_0011735    LinkOut: [ RefSeq ]
Other Transcripts NM_0027 , NM_2032   
Expression LinkOut: [ BioGPS ]
Putative miRNA Targets on POU5F1 LinkOut: [ TargetScan 5.1 | MicroCosm | miRNAMap 2.0 ]
3'UTR of POU5F1
(miRNA target sites are highlighted)
>POU5F1|NM_0011735|3'UTR
   1 TGAGGTGCCTGCCCTTCTAGGAATGGGGGACAGGGGGAGGGGAGGAGCTAGGGAAAGAAAACCTGGAGTTTGTGCCAGGG
  81 TTTTTGGGATTAAGTTCTTCATTCACTAAGGAAGGAATTGGGAACACAAAGGGTGGGGGCAGGGGAGTTTGGGGCAACTG
 161 GTTGGAGGGAAGGTGAAGTTCAATGATGCTCTTGATTTTAATCCCACATCATGTATCACTTTTTTCTTAAATAAAGAAGC
 241 CTGGGACACAGTAGATAGACACACTTAAAAAAAAAAA
Target sites Provided by authors  Predicted by miRanda
Experimental Support 1 for Functional miRNA-Target Interaction
miRNA:Target hsa-miR-145-5p :: POU5F1    [ Functional MTI ]
Validation Method FACS , Flow , GFP reporter assay , In situ hybridization , Luciferase reporter assay , qRT-PCR , Reporter assay;Western blot;qRT-PCR
Conditions H9
Location of target site 3'UTR
Tools used in this research miRanda , miRBase Target Database
Original Description (Extracted from the article) ... At 24 hr after transfection, there was signifi- cant repression on the wild-type 30 UTR luciferase reporter activities of OCT4 (p = 5.1x10^-5 ), SOX2 (p = 1.0x10^-5 ), and KLF4 (p = 1.2x10^-6 ) in comparison to the no-UTR control, and these effects persisted at 48 hr (Figures 2A–2C). In contrast, the mutant reporters with a 6 bp deletion of the miR-145 target sites had significantly less repression than the wild-type reporters (OCT4, p = 1.3x10^-7 ; SOX2, p = 0.03; KLF4, p = 0.002. Figures 2A–2C). ...

- Xu, N. Papagiannakopoulos, T. Pan, G. et al., 2009, Cell.

Article - Xu, N. Papagiannakopoulos, T. Pan, G. et al.
- Cell, 2009
MicroRNAs (miRNAs) are posttranscriptional modulators of gene expression and play an important role in many developmental processes. We report here that expression of microRNA-145 (miR-145) is low in self-renewing human embryonic stem cells (hESCs) but highly upregulated during differentiation. We identify the pluripotency factors OCT4, SOX2, and KLF4 as direct targets of miR-145 and show that endogenous miR-145 represses the 3' untranslated regions of OCT4, SOX2, and KLF4. Increased miR-145 expression inhibits hESC self-renewal, represses expression of pluripotency genes, and induces lineage-restricted differentiation. Loss of miR-145 impairs differentiation and elevates OCT4, SOX2, and KLF4. Furthermore, we find that the miR-145 promoter is bound and repressed by OCT4 in hESCs. This work reveals a direct link between the core reprogramming factors and miR-145 and uncovers a double-negative feedback loop involving OCT4, SOX2, KLF4, and miR-145.
LinkOut: [PMID: 19409607]
Experimental Support 2 for Functional miRNA-Target Interaction
miRNA:Target hsa-miR-145-5p :: POU5F1    [ Functional MTI ]
Validation Method Luciferase reporter assay
Conditions A549
Location of target site 3'UTR
Tools used in this research miRanda , TargetScan
Original Description (Extracted from the article) ... The predicted miR-145 binding site in OCT4 3’-untranslated region (UTR) was validated by dual-luciferase reporter gene assay. 双荧光素酶报告基因检测 对miR-145和OCT4的野 生型结合位点进行定点突变。miR-145模拟物和野生 型OCT4共转染组的Hela细胞荧光素酶活性下降约50% (P<0.001),而突变型转染组中荧光素酶活性无明显变 化,同时在miR-145阻遏物和阴性对照组中也未观察到有 荧光素酶活性的改变(图5),统计分析显示差异无统计 学意义。该结果表明miR-145可以直接调控OCT4基因。 ...

- Zhang, S. Wu, Y. Feng, D. Zhang, Z. Jiang, et al., 2011, Zhongguo fei ai za zhi = Chinese journal of lung cancer.

Article - Zhang, S. Wu, Y. Feng, D. Zhang, Z. Jiang, et al.
- Zhongguo fei ai za zhi = Chinese journal of lung cancer, 2011
BACKGROUND: MiR-145 functions as a protective miRNA identified in tumor tissues of lung adenocarcinoma patients. The aim of this study is to investigate the relationship between miR-145 and proliferation of lung cancer stem cells and involved molecular mechanisms in human lung adenocarcinaoma A549 cell line. METHODS: MicroRNA microarray technology was conducted to compare miRNA signature between tumor and adjacent normal tissue of lung adenocarcinaoma. The potential target gene of miR-145 was predicted by online bioinformatic softwares. Pre-miR-145 mimics and anti-miR-145 inhibitor were transfected into A549 cell line by lipofectamine 2000. miR-145 expression in each group was detected by real time PCR. The OCT4 protein level was analyzed by Western blot. The predicted miR-145 binding site in OCT4 3'-untranslated region (UTR) was validated by dual-luciferase reporter gene assay. CCK-8 assay was employed to observe the proliferation activity of A549 cells. The ratio of CD133 positive cells in each group was analyzed by flow cytometry. RESULTS: miR-145 expression was significantly down-regulated in lung adenocarcinoma compared with ajacent normal tissue. OCT4 is a potential target gene of miR-145 predicted by miRanda. Compared with control group, miR-145 was significantly up-regulated and down-regulated in the pre-miR-145 mimics and anti-miR-145 inhibitor groups respectively. Overexpression of miR-145 inhibited the proliferation of A549 cells. Both the OCT4 protein level and CD133 positive ratio were remarkably decreased in the pre-miR-145 mimics group, whereas significantly increased in the anti-miR-145 inhibitor group. Dual-luciferase reporter gene assay validated the predicted miR-145 binding site of OCT4 3'UTR. CONCLUSIONS: MiR-145 can inhibit the proliferation of lung cancer stem cells in A549 cell line via down-regulating OCT4 expression. MiR-145 is a potential protective miRNA of lung cancer.
LinkOut: [PMID: 21496429]
Experimental Support 3 for Functional miRNA-Target Interaction
miRNA:Target hsa-miR-145-5p :: POU5F1    [ Functional MTI ]
Validation Method Immunofluorescence , qRT-PCR
Conditions HSK
Location of target site 3'UTR
Tools used in this research None
Original Description (Extracted from the article) ... mir-145 regulates OCT4 expression in decitabine-treated HSK//Here, we report for the first time that the cancer treatment drug decitabine reactivates endogenous Oct4 and its regulator mir-145,in HSK. We also show for the first time that another cancer treatment drug, doxorubicin, induces expression of endogenous mir-145 only in cells that already express OCT4. ...

- Chinnathambi, S. Wiechert, S. et al., 2012, J Dermatol.

Article - Chinnathambi, S. Wiechert, S. et al.
- J Dermatol, 2012
Previously, we showed that transient transfection with OCT4 not only produced high expression of Oct4 in skin keratinocytes, but also caused a generalized demethylation of keratinocyte DNA. We hypothesized that DNA demethylation alone might allow expression of endogenous OCT4. Here, we report that treatment with the cancer drug decitabine results in generalized DNA demethylation in skin keratinocytes, and by 48 h after treatment, 96% of keratinocytes show expression of the endogenous Oct4 protein and the OCT4 repressor mir-145. This is true for keratinocytes only, as skin fibroblasts treated similarly show no OCT4 or mir-145 expression. Decitabine-treated keratinocytes also show increased mir-302c and proliferation similar to other Oct4(+) cells. Treatment with doxorubicin, another cancer drug, induces expression of mir-145 only in cells that already express OCT4, suggesting that Oct4 regulates its own repressor. Co-treatment with decitabine and doxorubicin results first in increased OCT4 and mir-145, then a decrease in both, suggesting that OCT4 and mir-145 regulate each other. The novel strategy presented here provides a regulatable system to produce Oct4(+) cells for transformation studies and provides a unique method to study the effects of endogenous Oct4 in cancer cells and the surrounding somatic cells.
LinkOut: [PMID: 22486352]
Experimental Support 4 for Functional miRNA-Target Interaction
miRNA:Target hsa-miR-145-5p :: POU5F1    [ Functional MTI ]
Validation Method Luciferase reporter assay
Conditions HEK293 , H1
Location of target site 3'UTR
Original Description (Extracted from the article) ... linc-RoR shares regulatory miRNAs with the core TFs Oct4, Sox2, and Nanog and that miR-145 may be one of the critical regulatory miRNAs for these genes. ...

- Wang, Y. Xu, Z. Jiang, J. Xu, C. Kang, J. et al., 2013, Dev Cell.

Article - Wang, Y. Xu, Z. Jiang, J. Xu, C. Kang, J. et al.
- Dev Cell, 2013
The embryonic stem cell (ESC) transcriptional and epigenetic networks are controlled by a multilayer regulatory circuitry, including core transcription factors (TFs), posttranscriptional modifier microRNAs (miRNAs), and some other regulators. However, the role of large intergenic noncoding RNAs (lincRNAs) in this regulatory circuitry and their underlying mechanism remains undefined. Here, we demonstrate that a lincRNA, linc-RoR, may function as a key competing endogenous RNA to link the network of miRNAs and core TFs, e.g., Oct4, Sox2, and Nanog. We show that linc-RoR shares miRNA-response elements with these core TFs and that linc-RoR prevents these core TFs from miRNA-mediated suppression in self-renewing human ESC. We suggest that linc-RoR forms a feedback loop with core TFs and miRNAs to regulate ESC maintenance and differentiation. These results may provide insights into the functional interactions of the components of genetic networks during development and may lead to new therapies for many diseases.
LinkOut: [PMID: 23541921]
MiRNA-Target Expression Profile:

 
MiRNA-Target Interaction Network:
Strong evidence (reporter assay, western blot, qRT-PCR or qPCR)
Other evidence
104 hsa-miR-145-5p Target Genes:
ID Target Description Validation methods
Strong evidence Less strong evidence
MIRT000305 BNIP3 BCL2/adenovirus E1B 19kDa interacting protein 3 4 1
MIRT000306 KLF5 Kruppel-like factor 5 (intestinal) 1 1
MIRT000307 SOX2 SRY (sex determining region Y)-box 2 4 2
MIRT000308 KLF4 Kruppel-like factor 4 (gut) 4 2
MIRT000426 MUC1 mucin 1, cell surface associated 4 2
MIRT000457 MYO6 myosin VI 4 1
MIRT000575 CDKN1A cyclin-dependent kinase inhibitor 1A (p21, Cip1) 4 1
MIRT000626 STAT1 signal transducer and activator of transcription 1, 91kDa 5 1
MIRT000627 YES1 v-yes-1 Yamaguchi sarcoma viral oncogene homolog 1 5 3
MIRT000676 CBFB core-binding factor, beta subunit 4 2
MIRT000677 PPP3CA protein phosphatase 3, catalytic subunit, alpha isozyme 4 1
MIRT000678 CLINT1 clathrin interactor 1 4 1
MIRT000731 IRS1 insulin receptor substrate 1 4 5
MIRT000732 PARP8 poly (ADP-ribose) polymerase family, member 8 2 2
MIRT001811 TMOD3 tropomodulin 3 (ubiquitous) 2 1
MIRT001917 HOXA9 homeobox A9 4 1
MIRT003325 EGFR epidermal growth factor receptor (erythroblastic leukemia viral (v-erb-b) oncogene homolog, avian) 3 2
MIRT003543 FSCN1 fascin homolog 1, actin-bundling protein (Strongylocentrotus purpuratus) 5 5
MIRT004290 MYC v-myc myelocytomatosis viral oncogene homolog (avian) 4 2
MIRT004496 FLI1 Friend leukemia virus integration 1 4 3
MIRT004580 DFFA DNA fragmentation factor, 45kDa, alpha polypeptide 4 1
MIRT004616 IFNB1 interferon, beta 1, fibroblast 3 1
MIRT004748 TIRAP toll-interleukin 1 receptor (TIR) domain containing adaptor protein 2 1
MIRT004904 POU5F1 POU class 5 homeobox 1 3 4
MIRT004931 IGF1R insulin-like growth factor 1 receptor 3 2
MIRT004938 KRT7 keratin 7 2 1
MIRT005683 PPM1D protein phosphatase, Mg2+/Mn2+ dependent, 1D 1 1
MIRT005688 C11orf9 chromosome 11 open reading frame 9 1 1
MIRT005689 CPEB4 cytoplasmic polyadenylation element binding protein 4 1 1
MIRT005690 FZD7 frizzled homolog 7 (Drosophila) 1 1
MIRT005809 ROBO2 roundabout, axon guidance receptor, homolog 2 (Drosophila) 3 1
MIRT005810 SRGAP1 SLIT-ROBO Rho GTPase activating protein 1 3 1
MIRT005878 EIF4E eukaryotic translation initiation factor 4E 3 1
MIRT005879 CDK4 cyclin-dependent kinase 4 3 1
MIRT006215 VEGFA vascular endothelial growth factor A 3 1
MIRT006317 SERPINE1 serpin peptidase inhibitor, clade E (nexin, plasminogen activator inhibitor type 1), member 1 3 1
MIRT006332 IRS2 insulin receptor substrate 2 1 1
MIRT006494 ITGB8 integrin, beta 8 4 1
MIRT006747 SWAP70 SWAP switching B-cell complex 70kDa subunit 4 2
MIRT006774 ESR1 estrogen receptor 1 1 1
MIRT006788 NUDT1 nudix (nucleoside diphosphate linked moiety X)-type motif 1 3 1
MIRT006847 JAG1 jagged 1 (Alagille syndrome) 4 1
MIRT006889 NEDD9 neural precursor cell expressed, developmentally down-regulated 9 3 2
MIRT006899 PAK4 p21 protein (Cdc42/Rac)-activated kinase 4 3 1
MIRT006903 DDX17 DEAD (Asp-Glu-Ala-Asp) box polypeptide 17 3 1
MIRT007094 ERG v-ets erythroblastosis virus E26 oncogene homolog (avian) 1 1
MIRT007107 NRAS neuroblastoma RAS viral (v-ras) oncogene homolog 2 1
MIRT007180 ILK integrin-linked kinase 3 1
MIRT007247 CTGF connective tissue growth factor 1 1
MIRT007248 SOCS7 suppressor of cytokine signaling 7 1 1
MIRT007257 MDM2 Mdm2 p53 binding protein homolog (mouse) 1 1
MIRT007275 ADAM17 ADAM metallopeptidase domain 17 1 1
MIRT007288 CDH2 cadherin 2, type 1, N-cadherin (neuronal) 2 1
MIRT007307 HDAC2 histone deacetylase 2 1 1
MIRT021492 FBXO28 F-box protein 28 1 1
MIRT021493 USP46 ubiquitin specific peptidase 46 1 1
MIRT021494 ACBD3 acyl-CoA binding domain containing 3 1 1
MIRT021495 ELK1 ELK1, member of ETS oncogene family 1 1
MIRT021496 CCNA2 cyclin A2 1 1
MIRT021497 C11orf58 chromosome 11 open reading frame 58 1 1
MIRT021498 CCDC25 coiled-coil domain containing 25 1 1
MIRT021499 RTKN rhotekin 4 1
MIRT021500 RASA1 RAS p21 protein activator (GTPase activating protein) 1 1 1
MIRT021501 F11R F11 receptor 2 2
MIRT021502 ARL6IP5 ADP-ribosylation-like factor 6 interacting protein 5 2 1
MIRT021503 AKR1B10 aldo-keto reductase family 1, member B10 (aldose reductase) 2 1
MIRT021504 C11orf65 chromosome 11 open reading frame 65 2 1
MIRT021505 HLTF helicase-like transcription factor 2 1
MIRT021506 GMFB glia maturation factor, beta 2 1
MIRT021507 SERINC5 serine incorporator 5 2 1
MIRT021508 MEST mesoderm specific transcript homolog (mouse) 2 1
MIRT021509 ALPPL2 alkaline phosphatase, placental-like 2 2 1
MIRT021510 NDRG2 NDRG family member 2 2 1
MIRT021511 DTD1 D-tyrosyl-tRNA deacylase 1 homolog (S. cerevisiae) 2 1
MIRT021512 TPM3 tropomyosin 3 2 1
MIRT021513 MAP2K6 mitogen-activated protein kinase kinase 6 2 1
MIRT021514 CEP19 chromosome 3 open reading frame 34 2 1
MIRT021515 TPRG1 tumor protein p63 regulated 1 2 1
MIRT021516 GOLM1 golgi membrane protein 1 2 1
MIRT021517 CCDC43 coiled-coil domain containing 43 2 1
MIRT021518 MMP1 matrix metallopeptidase 1 (interstitial collagenase) 2 1
MIRT021519 PTP4A2 protein tyrosine phosphatase type IVA, member 2 2 1
MIRT021520 TMEM9B TMEM9 domain family, member B 2 1
MIRT021521 MMP12 matrix metallopeptidase 12 (macrophage elastase) 2 1
MIRT021522 MTMR14 myotubularin related protein 14 2 1
MIRT021523 ALDH3A1 aldehyde dehydrogenase 3 family, member A1 2 1
MIRT021524 NDUFA4 NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 4, 9kDa 2 1
MIRT021525 FAM3C family with sequence similarity 3, member C 2 1
MIRT021526 LYPLA2 lysophospholipase II 2 1
MIRT021527 FAM45A family with sequence similarity 45, member A 2 1
MIRT021528 PIGF phosphatidylinositol glycan anchor biosynthesis, class F 2 1
MIRT021529 AP1G1 adaptor-related protein complex 1, gamma 1 subunit 2 1
MIRT021530 PHF17 PHD finger protein 17 2 1
MIRT021531 NIPSNAP1 nipsnap homolog 1 (C. elegans) 2 1
MIRT021532 KREMEN1 kringle containing transmembrane protein 1 2 1
MIRT021533 MMP14 matrix metallopeptidase 14 (membrane-inserted) 2 1
MIRT021534 ABRACL chromosome 6 open reading frame 115 2 1
MIRT021535 MIXL1 Mix1 homeobox-like 1 (Xenopus laevis) 2 1
MIRT021536 TSPAN6 tetraspanin 6 2 1
MIRT021537 PODXL podocalyxin-like 2 1
MIRT021538 APH1A anterior pharynx defective 1 homolog A (C. elegans) 2 1
MIRT021539 ABHD17C family with sequence similarity 108, member C1 2 1
MIRT035522 NANOG Nanog homeobox 1 1
MIRT035535 MYO5A myosin VA (heavy chain 12, myoxin) 1 1