Experimental Support 1 for Functional miRNA-Target Interaction
miRNA:Target
mmu-miR-125a-5p
-- Functional MTI --
Lin28a
Validation Method
miRNA effects on biological function
Article
- Wu L; Belasco JG
- Molecular and cellular biology , 2005
Vertebrate genomes each encode hundreds of micro-RNAs (miRNAs), yet for few of these miRNAs is there empirical evidence as to which mRNA(s) they regulate. Here we report the identification of human lin-28 mRNA as a regulatory target of human miR-125b and its homolog miR-125a. Studies of miR-125b function in mouse P19 embryonal carcinoma cells induced to develop into neurons suggest a role for this regulatory miRNA in mammalian neuronal differentiation, since its increased concentration in these cells contributes to lin-28 downregulation. Within the lin-28 3' untranslated region (UTR) are two conserved miRNA responsive elements (miREs) that mediate repression by miR-125b and miR-125a. Simultaneous deletion of both miREs renders the lin-28 3' UTR almost completely insensitive to these miRNAs, indicating that these two miREs are the principal elements in the lin-28 3' UTR that respond to miR-125. At the 3' end of each element is an adenosine residue that makes a significant contribution to function irrespective of its complementarity to the 5'-terminal nucleotide of miR-125. By contrast to most earlier reports of gene repression by other miRNAs that are imperfectly complementary to their targets, lin-28 downregulation by miR-125 involves reductions in both translational efficiency and mRNA abundance. The decrease in the mRNA concentration is achieved by a posttranscriptional mechanism that is independent of the inhibitory effect on translation.
LinkOut: [ PMID: 16227573 ]
28 mmu-miR-125a-5p Target Genes:
Functional analysis:
ID
Target
Description
Validation methods
Strong evidence
Less strong evidence
MIRT001716
Lin28a
lin-28 homolog A (C. elegans)
1
1
MIRT005597
Trim71
tripartite motif-containing 71
4
3
MIRT006310
Cbx7
chromobox 7
2
1
MIRT006967
4632428N05Rik
V-set immunoregulatory receptor
2
1
MIRT054177
Ptpn18
protein tyrosine phosphatase, non-receptor type 18
2
1
MIRT054178
Ptpn7
protein tyrosine phosphatase, non-receptor type 7
2
1
MIRT054179
Ppp1ca
protein phosphatase 1, catalytic subunit, alpha isoform
2
1
MIRT054180
Ppp2ca
protein phosphatase 2 (formerly 2A), catalytic subunit, alpha isoform
2
1
MIRT054570
Traf6
TNF receptor-associated factor 6
3
1
MIRT580227
Tspan12
tetraspanin 12
2
2
MIRT582368
Mtf1
metal response element binding transcription factor 1
2
2
MIRT582450
Mgat4a
mannoside acetylglucosaminyltransferase 4, isoenzyme A
2
2
MIRT584884
Antxr2
anthrax toxin receptor 2
2
2
MIRT587193
Foxk1
forkhead box K1
2
2
MIRT588848
Snrnp40
small nuclear ribonucleoprotein 40 (U5)
2
2
MIRT591275
Lars2
leucyl-tRNA synthetase, mitochondrial
2
4
MIRT592914
Madd
MAP-kinase activating death domain
2
2
MIRT594893
Il1rn
interleukin 1 receptor antagonist
2
4
MIRT596427
Hif1an
hypoxia-inducible factor 1, alpha subunit inhibitor
3
3
MIRT599142
Dqx1
DEAQ RNA-dependent ATPase
2
2
MIRT599717
Aph1c
aph1 homolog C, gamma secretase subunit
2
2
MIRT600832
Gm14137
predicted gene 14137
2
2
MIRT604902
Jmy
junction-mediating and regulatory protein
2
2
MIRT605441
Stat1
signal transducer and activator of transcription 1
2
2
MIRT606092
Wdr25
WD repeat domain 25
2
2
MIRT732537
Tnfrsf1b
tumor necrosis factor receptor superfamily, member 1b
4
0
MIRT734700
VDR
vitamin D receptor
2
0
MIRT734824
Sox11
SRY (sex determining region Y)-box 11
2
0
miRNA-Drug Associations
miRNA
Small Melocule
FDA
CID
Detection Method
Condition
PMID
Year
Expression Pattern of miRNA
miR-125a
Budesonide
approved
5281004
Microarray
neonatal mice liver
20145010
2010
down-regulated
miR-125a
Phenethyl isothiocyanate(PEITC)
NULL
16741
Microarray
neonatal mice lung
20145010
2010
down-regulated
miR-125a
Chaihu Shugan San
NULL
NULL
Microarray
hippocampus
23947143
2013
down-regualted
miR-125a
Perfluorooctane sulfonate
NULL
74483
Microarray
zebrafish embryos
20878907
2011
down-regulated
miR-125a
Hydroxamic acid HDACi LAQ824
NULL
NULL
Microarray
breast cancer cell line SKBr3
16452179
2006
up-regulated
miR-125a
Enoxacin
approved
3229
Quantitative real-time PCR
HEK293 cells
18641635
2008
up-regulated
miR-125a
4-hydroxynonenal
NULL
5283344
Microarray
human leukemic HL-60 cell
19022373
2009
up-regulated
miR-125a
Valproate
approved
3121
Quantitative real-time PCR
CD4+, CD25- T cells
20427269
2010
down-regulated
miR-125a
Formaldehyde
NULL
712
Microarray
Human lung epithelial cells (A549)
21147603
2011
down-regulated
miR-125a
Enoxacin
approved
3229
Northern blot
HCT-116 and RKO colon cancer cell lines
21368194
2011
up-regulated
miR-125a
Enoxacin
approved
3229
Quantitative real-time PCR
HCT-116 and RKO colon cancer cell lines
21368194
2011
up-regulated
miR-125a
5-aza-2'-deoxycytidine (5-Aza-CdR)
approved
451668
Microarray
breast cancer MDA-MB231
22076154
2011
down-regulated
miR-125a-5p
Hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX)
NULL
8490
Microarray
mouse brain
19270793
2009
up-regulated
miR-125a-5p
Hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX)
NULL
8490
Microarray
mouse liver
19270793
2009
down-regulated
miR-125a-5p
Curcumin
NULL
969516
Microarray
HONE1 cells
24896104
2014
down-regulated
miR-125a-5p
5-Fluorouracil
approved
3385
Microarray
MCF-7 breast cancer cells
21506117
2011
down-regulated
miR-125a-5p
Arsenic trioxide
approved
14888
Quantitative real-time PCR
acute promyelocytic leukemia
22072212
2012
up-regulated
miR-125a-5p
Trastuzumab
approved
NULL
Microarray
SKBR3 cells.
22384020
2012
up-regulated
miR-125a-5p
Glucocorticoid
NULL
NULL
TaqMan low-density array
Eosinophilic esophagitis
22815788
2012
up-regulated
miR-125a-5p
Marine fungal metabolite 1386A
NULL
NULL
Microarray
MCF-7 breast cancer cells.
22159329
2012
down-regulated
miRNA-Drug Resistance Associations
miRNA
Drug Name
CID
NSC
FDA
Effect/Pattern
Detection Method
Level
Phenotype
Condition
mmu-miR-125a-5p
Paclitaxel
36314
NSC125973
approved
sensitive
Low
Colon Cancer
tissue and cell line (HT-29)