Accession ID: MIRT004456 [miRNA, hsa-miR-152-3p :: DNMT1, target gene]
pre-miRNA Information
pre-miRNA ID hsa-mir-152LinkOut: [miRBase ]
Description Homo sapiens miR-152 stem-loop
Comment This miRNA sequence is predicted based on homology to a verified miRNA from mouse .
2nd Structure of pre-miRNA
Mature miRNA Information
Mature miRNA hsa-miR-152-3p
Evidence Experimental
Experiments Cloned
Putative hsa-miR-152-3p Targets LinkOut: [ TargetScanS 5.1 | MicroCosm | | miRecords | miRDB | miRo | miRNAMap 2.0 ]
Gene Information
Gene Symbol DNMT1 LinkOut: [ Entrez Gene | BioGPS | Wikipedia | iHop ]
Description DNA (cytosine-5-)-methyltransferase 1
Transcript NM_0011308    LinkOut: [ RefSeq ]
Other Transcripts NM_0013   
Expression LinkOut: [ BioGPS ]
Putative miRNA Targets on DNMT1 LinkOut: [ TargetScan 5.1 | MicroCosm | miRNAMap 2.0 ]
3'UTR of DNMT1
(miRNA target sites are highlighted)
Target sites Provided by authors  Predicted by miRanda
miRNA-target interactions (Predicted by miRanda)
IDDuplex structurePositionScoreMFE
miRNA  3' gguucaagacaGUACGUGACu 5'
Target 5' ggaatccccaaCATGCACTGa 3'
95 - 115 150.00 -16.01
            |||  ||:| |:|||||:|  
267 - 289 133.00 -10.50
             ||| || |::||||:|  
Target 5' tgcAGTACT-TTGTGCATTct 3'
240 - 259 125.00 -6.10
Experimental Support 1 for Functional miRNA-Target Interaction
miRNA:Target hsa-miR-152-3p :: DNMT1    [ Functional MTI ]
Validation Method Luciferase reporter assay ,
Conditions Mz-ChA-1
Location of target site 3'UTR
Tools used in this research miRBase Target Database , PicTar , TargetScan
Article - Braconi, C. Huang, N. Patel, T.
- Hepatology, 2010
Although the inflammation-associated cytokine interleukin-6 (IL-6) has been implicated in cholangiocarcinoma growth, the relationship between IL-6 and oncogenic changes is unknown. IL-6 can increase expression of DNA methyltransferase-1 (DNMT-1) and epigenetically regulate the expression of several genes, including microRNAs (miRNAs). DNMT-1 up-regulation occurs in hepatobiliary cancers and is associated with a poor prognosis. To understand the potential regulation of DNMT-1 by IL-6-dependent miRNAs, we examined the expression of a group of miRNAs which have sequence complementarity to the 3'-untranslated region of DNMT-1, namely miR-148a, miR-152, and miR-301. The expression of these miRNAs was decreased in cholangiocarcinoma cells. Moreover, the expression of all three miRNAs was decreased in IL-6-overexpressing malignant cholangiocytes in vitro and in tumor cell xenografts. There was a concomitant decrease in expression of the methylation-sensitive tumor suppressor genes Rassf1a and p16INK4a. Using luciferase reporter constructs, DNMT-1 was verified as a target for miR-148a and miR-152. Precursors to miR-148a and miR-152 decreased DNMT-1 protein expression, increased Rassf1a and p16INK4a expression, and reduced cell proliferation. Conclusion: These data indicate that IL-6 can regulate the activity of DNMT-1 and expression of methylation-dependent tumor suppressor genes by modulation of miR-148a and miR-152, and provide a link between this inflammation-associated cytokine and oncogenesis in cholangiocarcinoma. (HEPATOLOGY 2010.).
LinkOut: [PMID: 20146264]
Experimental Support 2 for Functional miRNA-Target Interaction
miRNA:Target hsa-miR-152-3p :: DNMT1    [ Functional MTI ]
Validation Method Luciferase reporter assay , qRT-PCR , Western blot , Reporter assay;Western blot;qRT-PCR
Conditions HepG2 , HepG2.2.15 , Huh-7 , LO2 , Hepa1-6
Disease hepatitis B virus related hepatocellular carcinoma;
Location of target site 3'UTR
Tools used in this research miRanda , mirGen , PicTar , TargetScan
Original Description (Extracted from the article) ... As shown in Fig. 3B, miR-152 significantly reduced the luciferase activity of the WT construct of the DNMT1 3'-UTR with respect to the negative control, whereas such a suppressive effect was not observed in cells with the Mut construct of DNMT1 3'-UTR.// ...

- Huang, J. Wang, Y. Guo, Y. Sun, S., 2010, Hepatology.

Article - Huang, J. Wang, Y. Guo, Y. Sun, S.
- Hepatology, 2010
The hepatitis B virus (HBV) X protein has been implicated as a potential trigger of the epigenetic modifications of some genes during hepatocarcinogenesis, but the underlying mechanisms remain unknown. MicroRNAs (miRNAs), which are noncoding RNAs that regulate gene expression, are involved in diverse biological functions and in carcinogenesis. In this study, we investigated whether some miRNAs are aberrantly expressed and involved in the regulation of the abnormal DNA methylation status in HBV-related hepatocellular carcinoma (HCC). Our results showed that the expression of microRNA-152 (miR-152) was frequently down-regulated in HBV-related HCC tissues in comparison with adjacent noncancerous hepatic tissues and was inversely correlated to DNA methyltransferase 1 (DNMT1) messenger RNA (mRNA) expression in HBV-related HCCs. The forced expression of miR-152 in liver cell lines resulted in a marked reduction of the expression of DNMT1 at both the mRNA and protein levels by directly targeting the 3' untranslated regions of DNMT1. This in turn led to a decrease in global DNA methylation, whereas inhibition of miR-152 caused global DNA hypermethylation and increased the methylation levels of two tumor suppressor genes, glutathione S-transferase pi 1 (GSTP1) and E-cadherin 1 (CDH1). Conclusion: Our findings suggest that miR-152 is frequently down-regulated and regulates DNMT1 in HBV-related HCC. These findings support a tumor-suppressive role of miR-152 in the epigenetic aberration of HBV-related HCC and the potential development of miRNA-based targeted approaches for the treatment of HBV-related HCC. HEPATOLOGY 2010.
LinkOut: [PMID: 20578129]
Experimental Support 3 for Functional miRNA-Target Interaction
miRNA:Target hsa-miR-152-3p :: DNMT1    [ Functional MTI ]
Validation Method Luciferase reporter assay , Microarray , qRT-PCR , Western blot
Conditions SK-N-BE(2) , KELLY
Location of target site 3'UTR
Original Description (Extracted from the article) ... Ectopic overexpression of miR-152, targeting DNMT1, also negatively affected cell invasiveness and anchorage-independent growth, contributing in part to the differentiated phenotype. ...

- Das, S. Foley, N. Bryan, K. Watters, K. M. et al., 2010, Cancer Res.

Article - Das, S. Foley, N. Bryan, K. Watters, K. M. et al.
- Cancer Res, 2010
Neuroblastoma is an often fatal pediatric cancer arising from precursor cells of the sympathetic nervous system. 13-Cis retinoic acid is included in the treatment regimen for patients with high-risk disease, and a similar derivative, all-trans-retinoic acid (ATRA), causes neuroblastoma cell lines to undergo differentiation. The molecular signaling pathways involved with ATRA-induced differentiation are complex, and the role that DNA methylation changes might play are unknown. The purpose of this study was to evaluate the genome-wide effects of ATRA on DNA methylation using methylated DNA immunoprecipitation applied to microarrays representing all known promoter and CpG islands. Four hundred and two gene promoters became demethylated, whereas 88 were hypermethylated post-ATRA. mRNA expression microarrays revealed that 82 of the demethylated genes were overexpressed by >2-fold, whereas 13 of the hypermethylated genes were underexpressed. Gene ontology analysis indicated that demethylated and re-expressed genes were enriched for signal transduction pathways, including NOS1, which is required for neural cell differentiation. As a potential mechanism for the DNA methylation changes, we show the downregulation of methyltransferases, DNMT1 and DNMT3B, along with the upregulation of endogenous microRNAs targeting them. Ectopic overexpression of miR-152, targeting DNMT1, also negatively affected cell invasiveness and anchorage-independent growth, contributing in part to the differentiated phenotype. We conclude that functionally important, miRNA-mediated DNA demethylation changes contribute to the process of ATRA-induced differentiation resulting in the activation of NOS1, a critical determinant of neural cell differentiation. Our findings illustrate the plasticity and dynamic nature of the epigenome during cancer cell differentiation.
LinkOut: [PMID: 20841484]
Experimental Support 4 for Functional miRNA-Target Interaction
miRNA:Target hsa-miR-152-3p :: DNMT1    [ Functional MTI ]
Validation Method Immunoblot , Immunoprecipitaion , Luciferase reporter assay , qRT-PCR , Western blot
Conditions 16HBE
Location of target site 3'UTR
Tools used in this research miRanda , PicTar , TargetScan
Original Description (Extracted from the article) ... miR-152 represses DNMT1 expression by targeting 3′-UTR ...

- Ji, W. Yang, L. Yuan, J. Yang, L. Zhang, M. et al., 2012, Carcinogenesis.

Article - Ji, W. Yang, L. Yuan, J. Yang, L. Zhang, M. et al.
- Carcinogenesis, 2012
Nickel (Ni) compounds are well-recognized human carcinogens, yet the molecular mechanisms by which they cause human cancer are still not well understood. MicroRNAs (miRNAs), which are small non-coding RNAs, are involved in diverse biological functions and carcinogenesis. In previous study, we identified upregulation of DNA methyltransferase 1 (DNMT1) expression in nickel sulfide (NiS)-transformed human bronchial epithelial (16HBE) cells. Here, we investigated whether some miRNAs are aberrantly expressed and targets DNMT1 in NiS-transformed cells. Our results showed that the expression of miRNA-152 (miR-152) was specifically downregulated in NiS-transformed cells via promoter DNA hypermethylation, whereas ectopic expression of miR-152 in NiS-transformed cells resulted in a marked reduction of DNMT1 expression. Further experiments revealed that miR-152 directly downregulated DNMT1 expression by targeting the 3' untranslated regions of its transcript. Interestingly, treatment of DNMT inhibitor, 5-aza-2-deoxycytidine, or depletion of DNMT1 led to increased miR-152 expression by reversion of promoter hypermethylation, DNMT1 and MeCP2 binding to miR-152 promoter in NiS-transformed cells. Moreover, inhibition of miR-152 expression in 16HBE cells could increase DNMT1 expression and result in an increase in DNA methylation, DNMT1 and MeCP2 binding to miR-152 promoter, indicating an interaction between miR-152 and DNMT1 is regulated by a double-negative circuit. Furthermore, ectopic expression of miR-152 in NiS-transformed cells led to a significant decrease of cell growth. Conversely, inhibition of miR-152 expression in 16HBE cells significantly increased cell growth. Taken together, these observations demonstrate a crucial functional crosstalk between miR-152 and the DNMT1 via a feedback loop involved in NiS-induced malignant transformation.
LinkOut: [PMID: 23125218]
Experimental Support 5 for Functional miRNA-Target Interaction
miRNA:Target hsa-miR-152-3p :: DNMT1    [ Functional MTI ]
Validation Method
Article - Xiang, Y. Ma, N. Wang, D. Zhang, Y. Zhou, et al.
- Oncogene, 2013
Epithelial ovarian cancer (EOC) is a highly lethal gynaecological malignancy. Cisplatin is the basal chemotherapeutic agent used to treat EOC, but resistance to cisplatin leads to chemotherapy failure. MicroRNAs are a novel class of regulators that function by controlling gene expression at the post-transcriptional level. Several recent reports have identified some microRNAs that are related to chemotherapy sensitivity. In this study, we found two microRNAs miR-152 and miR-185 that were significantly downregulated in the cisplatin-resistant ovarian cell lines SKOV3/DDP and A2780/DDP, compared with their sensitive parent line SKOV3 and A2780, respectively. Subsequently, the roles of miR-152 and miR-185 were evaluated in vitro and in vivo. The overexpression of miR-152 or miR-185 increased cisplatin sensitivity of SKOV3/DDP and A2780/DDP cells by inhibiting proliferation and promoting apoptosis, then we further confirmed that these miRNAs functioned through suppressing DNA methyltransferase 1 (DNMT1) directly. Concordantly, CD-1/CD-1 nude mice that were injected intraperitoneally with SKOV3/DDP cells transfected with miR-152 mimics exhibited upregulated cisplatin sensitivity in vivo. Interestingly, we found that there were no significant changes in the expression of these two microRNAs after treatment with decitabine (DAC), a traditional epigenetic therapeutic agent, suggesting these miRNAs represented two new regulators independent of DAC. Finally, the survival assay in A549 and HepG2 cells revealed that the two microRNAs involved in cisplatin sensitivity were related to cell types. Our results indicated that miR-152 and miR-185 were involved in ovarian cancer cisplatin resistance in vitro and in vivo by targeting DNMT1 directly. These molecules may serve as potential epigenetic therapeutic targets in other cancers.Oncogene advance online publication, 14 January 2013; doi:10.1038/onc.2012.575.
LinkOut: [PMID: 23318422]
MiRNA-Target Expression Profile:

MiRNA-Target Expression Profile(TCGA):

MiRNA-Target Interaction Network:
Strong evidence (reporter assay, western blot, qRT-PCR or qPCR)
Other evidence
132 hsa-miR-152-3p Target Genes:
ID Target Description Validation methods
Strong evidence Less strong evidence
MIRT000293 HLA-G major histocompatibility complex, class I, G 2 1
MIRT004456 DNMT1 DNA (cytosine-5-)-methyltransferase 1 5 5
MIRT006860 IRS1 insulin receptor substrate 1 2 1
MIRT006861 IGF1R insulin-like growth factor 1 receptor 2 1
MIRT035552 TGFA transforming growth factor, alpha 1 1
MIRT045818 SETDB1 SET domain, bifurcated 1 1 1
MIRT045819 ECHS1 enoyl CoA hydratase, short chain, 1, mitochondrial 1 1
MIRT045820 R3HCC1L R3H domain and coiled-coil containing 1-like 1 1
MIRT045821 HS6ST2 heparan sulfate 6-O-sulfotransferase 2 1 1
MIRT053040 ITGA5 integrin, alpha 5 (fibronectin receptor, alpha polypeptide) 3 1
MIRT053188 CSF1 colony stimulating factor 1 (macrophage) 2 1
MIRT053380 CCKBR cholecystokinin B receptor 2 1
MIRT053524 KRAS v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog 2 1
MIRT054136 CD151 CD151 molecule (Raph blood group) 3 1
MIRT054376 WNT1 wingless-type MMTV integration site family, member 1 3 1
MIRT054717 ADAM17 ADAM metallopeptidase domain 17 3 2
MIRT057495 CEP55 centrosomal protein 55kDa 1 2
MIRT062710 MLEC malectin 1 2
MIRT074396 TNRC6A trinucleotide repeat containing 6A 1 1
MIRT080877 RAB12 RAB12, member RAS oncogene family 1 1
MIRT083128 BTBD3 BTB (POZ) domain containing 3 1 6
MIRT097461 PAPD4 PAP associated domain containing 4 1 1
MIRT105306 VPS37A vacuolar protein sorting 37 homolog A (S. cerevisiae) 1 1
MIRT130085 TXNIP thioredoxin interacting protein 1 2
MIRT138430 KIF2C kinesin family member 2C 1 1
MIRT152417 ARID3A AT rich interactive domain 3A (BRIGHT-like) 1 1
MIRT155756 SIK1 salt-inducible kinase 1 1 3
MIRT210298 ARL8B ADP-ribosylation factor-like 8B 1 1
MIRT218523 HLA-A major histocompatibility complex, class I, A 1 1
MIRT222272 CCT6A chaperonin containing TCP1, subunit 6A (zeta 1) 1 1
MIRT270938 GPRC5A G protein-coupled receptor, family C, group 5, member A 1 1
MIRT280557 GLRX5 glutaredoxin 5 1 1
MIRT296528 STX16 syntaxin 16 1 1
MIRT301574 TNRC6B trinucleotide repeat containing 6B 1 1
MIRT320177 ITGB8 integrin, beta 8 1 1
MIRT347401 CEBPG CCAAT/enhancer binding protein (C/EBP), gamma 1 1
MIRT354161 RMND5A required for meiotic nuclear division 5 homolog A (S. cerevisiae) 2 1
MIRT382245 SH3PXD2A SH3 and PX domains 2A 1 1
MIRT399585 RBM38 RNA binding motif protein 38 1 1
MIRT437636 PHACTR2 phosphatase and actin regulator 2 3 2
MIRT437637 EMP1 epithelial membrane protein 1 2 1
MIRT437638 MXD1 MAX dimerization protein 1 2 1
MIRT437639 STRADB STE20-related kinase adaptor beta 2 1
MIRT437640 B4GALT5 UDP-Gal:betaGlcNAc beta 1,4- galactosyltransferase, polypeptide 5 2 1
MIRT437641 MOSPD1 motile sperm domain containing 1 2 1
MIRT437642 C18orf25 chromosome 18 open reading frame 25 2 1
MIRT437643 CLOCK clock homolog (mouse) 2 1
MIRT437644 KIAA0232 KIAA0232 2 1
MIRT438305 KLF4 Kruppel-like factor 4 (gut) 3 1
MIRT438378 FGF2 fibroblast growth factor 2 (basic) 2 1
MIRT438419 FGFR3 fibroblast growth factor receptor 3 4 1
MIRT438422 TACC3 transforming, acidic coiled-coil containing protein 3 4 1
MIRT438425 MAFB v-maf musculoaponeurotic fibrosarcoma oncogene homolog B (avian) 4 1
MIRT438428 CCND1 cyclin D1 4 1
MIRT448955 CDK19 cyclin-dependent kinase 19 1 1
MIRT453162 CNOT4 CCR4-NOT transcription complex, subunit 4 1 3
MIRT456194 ZDHHC6 zinc finger, DHHC-type containing 6 1 1
MIRT458101 TTLL1 tubulin tyrosine ligase-like family, member 1 1 1
MIRT459956 POC1A POC1 centriolar protein homolog A (Chlamydomonas) 1 1
MIRT461327 MRPS27 mitochondrial ribosomal protein S27 1 1
MIRT462846 B4GALT7 xylosylprotein beta 1,4-galactosyltransferase, polypeptide 7 1 1
MIRT463245 ZIC5 Zic family member 5 1 1
MIRT464039 WASL Wiskott-Aldrich syndrome-like 1 1
MIRT466870 STX6 syntaxin 6 1 1
MIRT467452 SNAPIN SNAP-associated protein 1 1
MIRT467695 SLC38A2 solute carrier family 38, member 2 1 2
MIRT468657 SECISBP2L SECIS binding protein 2-like 1 3
MIRT468919 RPS6KA4 ribosomal protein S6 kinase, 90kDa, polypeptide 4 1 1
MIRT469505 RCC2 regulator of chromosome condensation 2 1 1
MIRT469817 RAB14 RAB14, member RAS oncogene family 1 1
MIRT470327 PPP6R1 protein phosphatase 6, regulatory subunit 1 1 1
MIRT473768 MAP3K9 mitogen-activated protein kinase kinase kinase 9 1 1
MIRT477361 EOGT EGF domain-specific O-linked N-acetylglucosamine (GlcNAc) transferase 1 2
MIRT478216 DDX6 DEAD (Asp-Glu-Ala-Asp) box helicase 6 1 1
MIRT479813 CCNA2 cyclin A2 1 3
MIRT484937 ZFYVE26 zinc finger, FYVE domain containing 26 1 2
MIRT485434 KLF6 Kruppel-like factor 6 1 1
MIRT485646 DICER1 dicer 1, ribonuclease type III 1 2
MIRT487936 HLA-C major histocompatibility complex, class I, C 1 1
MIRT488935 ETV7 ets variant 7 1 1
MIRT492822 PATL1 protein associated with topoisomerase II homolog 1 (yeast) 1 1
MIRT494318 CDKN1B cyclin-dependent kinase inhibitor 1B (p27, Kip1) 1 2
MIRT496747 PDIK1L PDLIM1 interacting kinase 1 like 1 1
MIRT497882 SLC12A7 solute carrier family 12 (potassium/chloride transporters), member 7 1 1
MIRT500917 STARD13 StAR-related lipid transfer (START) domain containing 13 1 2
MIRT503175 AGO2 eukaryotic translation initiation factor 2C, 2 1 2
MIRT505103 YWHAB tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, beta polypeptide 1 1
MIRT505254 UBE2D3 ubiquitin-conjugating enzyme E2D 3 1 1
MIRT511219 LNPEP leucyl/cystinyl aminopeptidase 1 2
MIRT511895 GAS1 growth arrest-specific 1 1 3
MIRT513207 RFT1 RFT1 homolog (S. cerevisiae) 1 1
MIRT513615 VPS37B vacuolar protein sorting 37 homolog B (S. cerevisiae) 1 1
MIRT522802 KPNA4 karyopherin alpha 4 (importin alpha 3) 1 2
MIRT525441 RBM23 RNA binding motif protein 23 1 1
MIRT530300 AKAP17A A kinase (PRKA) anchor protein 17A 1 1
MIRT531687 MYO3A myosin IIIA 1 1
MIRT537298 FZD5 frizzled family receptor 5 1 1
MIRT541129 RAB34 RAB34, member RAS oncogene family 1 1
MIRT541197 HSP90AA1 heat shock protein 90kDa alpha (cytosolic), class A member 1 1 1
MIRT544730 NDRG1 N-myc downstream regulated 1 1 1
MIRT549175 BMP3 bone morphogenetic protein 3 1 1
MIRT549229 BAZ2B bromodomain adjacent to zinc finger domain, 2B 1 1
MIRT551862 ASB6 ankyrin repeat and SOCS box containing 6 1 1
MIRT559685 AGO3 eukaryotic translation initiation factor 2C, 3 1 1
MIRT561659 RNF219 ring finger protein 219 1 1
MIRT561857 NPTX1 neuronal pentraxin I 1 1
MIRT565735 SESN3 sestrin 3 1 1
MIRT566566 OTUD4 OTU domain containing 4 1 1
MIRT567184 IGFBP5 insulin-like growth factor binding protein 5 1 1
MIRT567836 DCUN1D3 DCN1, defective in cullin neddylation 1, domain containing 3 (S. cerevisiae) 1 1
MIRT574796 FAM104A family with sequence similarity 104, member A 1 1
MIRT576771 Tmem127 transmembrane protein 127 1 1
MIRT610543 WNT2B wingless-type MMTV integration site family, member 2B 1 2
MIRT613040 FOXP1 forkhead box P1 1 1
MIRT615071 COLEC12 collectin sub-family member 12 1 1
MIRT617479 AP5B1 adaptor-related protein complex 5, beta 1 subunit 1 1
MIRT625514 PPAPDC1A phosphatidic acid phosphatase type 2 domain containing 1A 1 1
MIRT628639 ABLIM1 actin binding LIM protein 1 1 1
MIRT630232 SORD sorbitol dehydrogenase 1 1
MIRT635944 PLA2G12A phospholipase A2, group XIIA 1 1
MIRT643722 MCMDC2 minichromosome maintenance domain containing 2 1 1
MIRT646774 IL23R interleukin 23 receptor 1 1
MIRT648161 CHRFAM7A CHRNA7 (cholinergic receptor, nicotinic, alpha 7, exons 5-10) and FAM7A (family with sequence similarity 7A, exons A-E) fusion 1 1
MIRT653242 SOS2 son of sevenless homolog 2 (Drosophila) 1 1
MIRT661180 S1PR2 sphingosine-1-phosphate receptor 2 1 1
MIRT693232 KIAA0907 KIAA0907 1 2
MIRT693774 VGLL2 vestigial like 2 (Drosophila) 1 1
MIRT702591 JARID2 jumonji, AT rich interactive domain 2 1 1
MIRT715173 DTX4 deltex homolog 4 (Drosophila) 1 1
MIRT722869 FAM212B family with sequence similarity 212, member B 1 1
MIRT723138 YPEL1 yippee-like 1 (Drosophila) 1 1
MIRT723184 OVOL1 ovo-like 1(Drosophila) 1 1
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