MicroRNAs in cardiomyocyte hypertrophy (Homo sapiens)

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2112285521452105885685Cellular ProteinsHypertrophic gene transcriptionProtein SynthesisNucleusTNFRG-beta-gammaRTKsGq/11PI3KStretchGPCRStressGC-AStressRCAN1 promotorPol IITranscription FactorsRASSarcomere organizationRhoCatecholaminesGPCRCell MembraneTGFR/Activinhsa-mir-199a-1hsa-mir-125b-2ET-1MEK6PKC-betahsa-mir-199a-1LIFMAPKKKPKC-betahsa-mir-195hsa-mir-15bhsa-mir-15bhsa-let-7bMEK7ROCK1hsa-mir-21PDK1hsa-mir-195PIK3CDhsa-mir-133a-1hsa-mir-199a-2TNF-alphahsa-mir-185FGFR2hsa-mir-27bmTORhsa-mir-133a-1hsa-let-7bhsa-mir-140PLChsa-mir-23aRAF1hsa-mir-30eNFAT3LRP6hsa-mir-199a-2MAPKKKCalNBCalciumhsa-mir-15bHDAC 9hsa-mir-130bhsa-mir-195hsa-mir-133a-2MEK4hsa-mir-133a-2p38FGF2CamKhsa-mir-27bRCAN1HDAC 4hsa-let-7bhsa-mir-15bhsa-mir-21hsa-mir-133bhsa-mir-140hsa-mir-27bSOCSHDAC 9hsa-mir-199a-1CT-1hsa-mir-199a-2NIKIGF-1 Rhsa-mir-103-2-asMEK2hsa-mir-15bPIK3CBhsa-let-7bhsa-mir-195hsa-mir-195hsa-mir-103-1-ashsa-mir-125b-1hsa-mir-23aRhoACalmodulinhsa-mir-23aGATA4PDKhsa-mir-195hsa-mir-27bhsa-mir-125b-1hsa-mir-195HDAC 7MAPKKKhsa-let-7bhsa-mir-199a-2hsa-mir-30ehsa-mir-125b-2PIK3CAERK2hsa-mir-185MEK3ERK1hsa-mir-27bFZD1CDK 9I-kappa-Bhsa-mir-15bLRP5PLA2hsa-mir-208ahsa-mir-125b-1hsa-mir-23ahsa-let-7bhsa-mir-103-2-asPIK3R1hsa-mir-133bHDAC 4hsa-mir-130bGSK3-betaCalmodulinhsa-mir-15bEGFhsa-mir-140NF-kappa-Bhsa-mir-30ehsa-mir-30eIP3MLCK3STAT3hsa-mir-23aAng IIhsa-mir-23aDAGMAPKKKKAKT2hsa-mir-214hsa-mir-208aMEK1IGFIDvl1hsa-mir-27bAng IIhsa-mir-125b-2hsa-mir-27bhsa-mir-21AKT1MEF-2ROCK2BNPhsa-mir-15bhsa-mir-30ePIK3R3Calciumhsa-mir-199a-1hsa-mir-30eJNKhsa-mir-27bhsa-mir-199a-2hsa-mir-23ahsa-mir-30ehsa-mir-208aBeta-cateninNF-kappa-Bhsa-mir-195hsa-mir-130bWNT5Ahsa-mir-15bMLCK1hsa-mir-195CalciumHDAC 5NFAT3IKKgCDK 7NeuregulinERK2hsa-mir-21WNT3AERK1HDAC 7IKKahsa-mir-103-1-ashsa-mir-133a-1hsa-mir-27bhsa-mir-15bANPgp130hsa-mir-199a-1PKG IPIK3CGNFAT3Cyclic GMPp38hsa-mir-195IKKbhsa-mir-15bhsa-mir-199a-1hsa-mir-27beIF2Bεhsa-mir-27bhsa-mir-15bhsa-mir-30ehsa-mir-195hsa-mir-125b-1GSK3-betahsa-mir-23aERK5TAK1hsa-mir-195hsa-mir-199a-2hsa-mir-199a-2MEK5hsa-mir-15bHDAC 5CalNAJNKPIK3R2Rac1STAT3hsa-mir-30ehsa-mir-133bFZD2hsa-mir-133a-2hsa-mir-195hsa-mir-199a-1TGF-betahsa-mir-125b-2


This pathway shows the role of microRNAs in the process of cardiac hypertrophy.

MicroRNA targets were predicted by the TargetScan algorithm, and the predicted interactions are shown in red dashed lines. MicroRNAs are shown as purple rounded rectangles.

It is not sure which WNT and frizzled proteins influence cardiac hypertrophy. Though there are strong indications that WNT3A, WNT5A, frizzled1 and frizzled2 play a role in cardiac hypertrophy. Thus these have been added to the pathway instead of all the WNT and frizzled proteins. Experiments which will shed light on this are still being done.

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Ontology Terms



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  1. Olson EN, Molkentin JD; ''Prevention of cardiac hypertrophy by calcineurin inhibition: hope or hype?''; Circ Res, 1999 PubMed
  2. Heineke J, Molkentin JD; ''Regulation of cardiac hypertrophy by intracellular signalling pathways.''; Nat Rev Mol Cell Biol, 2006 PubMed
  3. Molkentin JD, Lu JR, Antos CL, Markham B, Richardson J, Robbins J, Grant SR, Olson EN; ''A calcineurin-dependent transcriptional pathway for cardiac hypertrophy.''; Cell, 1998 PubMed
  4. Jalili T, Takeishi Y, Walsh RA; ''Signal transduction during cardiac hypertrophy: the role of G alpha q, PLC beta I, and PKC.''; Cardiovasc Res, 1999 PubMed
  5. Blankesteijn WM, van de Schans VA, ter Horst P, Smits JF; ''The Wnt/frizzled/GSK-3 beta pathway: a novel therapeutic target for cardiac hypertrophy.''; Trends Pharmacol Sci, 2008 PubMed
  6. Lim HW, Molkentin JD; ''Calcineurin and human heart failure.''; Nat Med, 1999 PubMed
  7. Clerk A, Sugden PH; ''Small guanine nucleotide-binding proteins and myocardial hypertrophy.''; Circ Res, 2000 PubMed
  8. Haghikia A, Stapel B, Hoch M, Hilfiker-Kleiner D; ''STAT3 and cardiac remodeling.''; Heart Fail Rev, 2010 PubMed
  9. Wollert KC, Taga T, Saito M, Narazaki M, Kishimoto T, Glembotski CC, Vernallis AB, Heath JK, Pennica D, Wood WI, Chien KR; ''Cardiotrophin-1 activates a distinct form of cardiac muscle cell hypertrophy. Assembly of sarcomeric units in series VIA gp130/leukemia inhibitory factor receptor-dependent pathways.''; J Biol Chem, 1996 PubMed
  10. Carè A, Catalucci D, Felicetti F, Bonci D, Addario A, Gallo P, Bang ML, Segnalini P, Gu Y, Dalton ND, Elia L, Latronico MV, Høydal M, Autore C, Russo MA, Dorn GW 2nd, Ellingsen O, Ruiz-Lozano P, Peterson KL, Croce CM, Peschle C, Condorelli G; ''MicroRNA-133 controls cardiac hypertrophy.''; Nat Med, 2007 PubMed
  11. Vanhaesebroeck B, Alessi DR; ''The PI3K-PDK1 connection: more than just a road to PKB.''; Biochem J, 2000 PubMed
  12. Molkentin JD; ''Calcineurin and beyond: cardiac hypertrophic signaling.''; Circ Res, 2000 PubMed
  13. Wang Y, Su B, Sah VP, Brown JH, Han J, Chien KR; ''Cardiac hypertrophy induced by mitogen-activated protein kinase kinase 7, a specific activator for c-Jun NH2-terminal kinase in ventricular muscle cells.''; J Biol Chem, 1998 PubMed
  14. Wang J, Xu R, Lin F, Zhang S, Zhang G, Hu S, Zheng Z; ''MicroRNA: novel regulators involved in the remodeling and reverse remodeling of the heart.''; Cardiology, 2009 PubMed
  15. Bueno OF, De Windt LJ, Tymitz KM, Witt SA, Kimball TR, Klevitsky R, Hewett TE, Jones SP, Lefer DJ, Peng CF, Kitsis RN, Molkentin JD; ''The MEK1-ERK1/2 signaling pathway promotes compensated cardiac hypertrophy in transgenic mice.''; EMBO J, 2000 PubMed
  16. Takeishi Y, Ping P, Bolli R, Kirkpatrick DL, Hoit BD, Walsh RA; ''Transgenic overexpression of constitutively active protein kinase C epsilon causes concentric cardiac hypertrophy.''; Circ Res, 2000 PubMed
  17. Wollert KC, Chien KR; ''Cardiotrophin-1 and the role of gp130-dependent signaling pathways in cardiac growth and development.''; J Mol Med, 1997 PubMed


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89794view10:54, 6 October 2016Mkutmonfixed special character in datanode label
84696view21:04, 15 March 2016KhanspersQuick edit to datanode annotation or property
84695view21:03, 15 March 2016KhanspersQuick edit to datanode annotation or property
75258view21:11, 13 May 2014Khansperschanged data nodes from gene product to rna
75252view20:57, 13 May 2014Khanspersupdated xrefs for mirs
74529view21:45, 29 April 2014AlexanderPicofixed unsupported characters in datanode labels
73325view20:39, 20 January 2014MaintBotFixed GraphId that incidentally overlapped with a GroupId!?
72027view12:54, 24 October 2013Mkutmonfixed unconnected lines
70090view18:00, 12 July 2013MaintBotupdating to 2013 schema
67463view11:05, 26 June 2013DdiglesOntology Term : 'hypertrophic cardimyopathy pathway' added !
59101view22:12, 21 February 2013MaintBotUpdated Ensembl data source
45381view21:47, 7 October 2011KhanspersOntology Term : 'heart disease' added !
44907view10:26, 6 October 2011MartijnVanIerselOntology Term : 'miRNA pathway' added !
41050view23:16, 1 March 2011MaintBotRemoved redundant pathway information and comments
37611view11:02, 14 June 2010MLevelsModified description
37610view10:59, 14 June 2010MLevelsChanged Lines
37553view12:58, 10 June 2010MLevelsMoved some microRNAs
37552view12:56, 10 June 2010MLevelsAdded some microRNAs
37551view12:46, 10 June 2010MLevelsPeriodical save, work in progress
37541view10:54, 10 June 2010MLevelsDeleted non-canonical wnt
37534view13:14, 9 June 2010MLevelsNon-Canonical Wnt Pathway
37438view09:20, 4 June 2010MLevelsMicroRNAs added
37407view12:04, 1 June 2010MLevelsMinor Changes
37406view11:57, 1 June 2010MLevelsPeriodical save, work in progress
37399view11:28, 1 June 2010MLevelsPeriodical save, work in progress
37395view10:45, 1 June 2010MLevelsAdded WNT pathway
37393view10:38, 1 June 2010MLevelsModified description
37392view10:12, 1 June 2010MLevelsPeriodical save, work in progress
37391view10:01, 1 June 2010MLevelsPeriodical save, work in progress
37388view09:51, 1 June 2010MLevelsPeriodical save, work in progress
37387view09:12, 1 June 2010MLevelsModified description
37345view08:49, 28 May 2010MLevelsPeriodical save, work in progress
37344view08:35, 28 May 2010MLevelsPeriodical save, work in progress
37343view08:22, 28 May 2010MLevelsPeriodical save, work in progress
37342view08:12, 28 May 2010MLevelsPeriodical save, work in progress
37341view08:02, 28 May 2010MLevelsPeriodical save, work in progress
37340view07:51, 28 May 2010MLevelsPeriodical save, work in progress
37336view14:16, 27 May 2010MLevelsMicroRNAs added
37335view14:06, 27 May 2010MLevelsPeriodical save, work in progress
37334view13:56, 27 May 2010MLevelsPeriodical save, work in progress
37333view13:46, 27 May 2010MLevelsPeriodical save, work in progress
37332view13:34, 27 May 2010MLevelsPeriodical save, work in progress
37331view13:24, 27 May 2010MLevelsPeriodical save, work in progress
37330view13:13, 27 May 2010MLevelsPeriodical save, work in progress
37329view13:02, 27 May 2010MLevelsPeriodical save, work in progress
37328view12:32, 27 May 2010MLevelsPeriodical save, work in progress
37327view12:21, 27 May 2010MLevelsPeriodical save, work in progress
37326view12:11, 27 May 2010MLevelsPeriodical save, work in progress
37295view08:42, 25 May 2010MLevelsColored Line
37294view08:41, 25 May 2010MLevelsID

External references


View all...
NameTypeDatabase referenceComment
AKT1GeneProduct207 (Entrez Gene)
AKT2GeneProduct208 (Entrez Gene)
ANPGeneProduct4878 (Entrez Gene)
Ang IIGeneProduct183 (Entrez Gene)
BNPGeneProduct4879 (Entrez Gene)
Beta-cateninGeneProduct1499 (Entrez Gene)
CDK 7GeneProduct1022 (Entrez Gene)
CDK 9GeneProduct1025 (Entrez Gene)
CT-1GeneProduct1489 (Entrez Gene)
CalNAGeneProduct5530 (Entrez Gene)
CalNBGeneProduct5532 (Entrez Gene)
CalciumMetaboliteHMDB00464 (HMDB)
CalmodulinProtein801 (Entrez Gene)
CamKGeneProduct817 (Entrez Gene)
Cyclic GMPMetaboliteHMDB01314 (HMDB)
DAGMetaboliteHMDB07009 (HMDB)
Dvl1GeneProduct1855 (Entrez Gene)
EGFGeneProduct1950 (Entrez Gene)
ERK1GeneProduct5595 (Entrez Gene)
ERK2GeneProduct5594 (Entrez Gene)
ERK5GeneProduct5598 (Entrez Gene)
ET-1GeneProduct1906 (Entrez Gene)
FGF2GeneProduct2247 (Entrez Gene)
FGFR2GeneProduct2263 (Entrez Gene)
FZD1GeneProduct8321 (Entrez Gene)
FZD2GeneProduct2535 (Entrez Gene)
GATA4GeneProduct2626 (Entrez Gene)
GSK3-betaGeneProduct2932 (Entrez Gene)
HDAC 4GeneProduct9759 (Entrez Gene)
HDAC 5GeneProduct10014 (Entrez Gene)
HDAC 7GeneProduct51564 (Entrez Gene)
HDAC 9GeneProduct9734 (Entrez Gene)
I-kappa-BGeneProduct9641 (Entrez Gene)
IGF-1 RGeneProduct3480 (Entrez Gene)
IGFIGeneProduct3479 (Entrez Gene)
IKKaGeneProduct1147 (Entrez Gene)
IKKbGeneProduct3551 (Entrez Gene)
IKKgGeneProduct8517 (Entrez Gene)
IP3MetaboliteHMDB01498 (HMDB)
JNKGeneProduct5599 (Entrez Gene)
LIFGeneProduct3976 (Entrez Gene)
LRP5GeneProduct4041 (Entrez Gene)
LRP6GeneProduct4040 (Entrez Gene)
MAPKKKGeneProduct5595 (Entrez Gene)
MAPKKKKGeneProduct5596 (Entrez Gene)
MEF-2GeneProduct50804 (Entrez Gene)
MEK1GeneProduct5604 (Entrez Gene)
MEK2GeneProduct5605 (Entrez Gene)
MEK3GeneProduct5606 (Entrez Gene)
MEK4GeneProduct6416 (Entrez Gene)
MEK5GeneProduct5607 (Entrez Gene)
MEK6GeneProduct5608 (Entrez Gene)
MEK7GeneProduct5609 (Entrez Gene)
MLCK1GeneProduct4638 (Entrez Gene)
MLCK3GeneProduct91807 (Entrez Gene)
NF-kappa-BGeneProduct4790 (Entrez Gene)
NFAT3GeneProduct4776 (Entrez Gene)
NIKGeneProduct9020 (Entrez Gene)
NeuregulinGeneProduct3084 (Entrez Gene)
PDK1GeneProduct5170 (Entrez Gene)
PDKGeneProduct5170 (Entrez Gene)
PIK3CAGeneProduct5290 (Entrez Gene)
PIK3CBGeneProduct5291 (Entrez Gene)
PIK3CDGeneProduct5293 (Entrez Gene)
PIK3CGGeneProduct5294 (Entrez Gene)
PIK3R1GeneProduct5295 (Entrez Gene)
PIK3R2GeneProduct5296 (Entrez Gene)
PIK3R3GeneProduct8503 (Entrez Gene)
PKC-betaGeneProduct5579 (Entrez Gene)
PKG IGeneProduct5592 (Entrez Gene)
PLA2GeneProduct5320 (Entrez Gene)
PLCGeneProduct5330 (Entrez Gene)
RAF1GeneProduct5894 (Entrez Gene)
RCAN1GeneProduct1827 (Entrez Gene)
ROCK1GeneProduct6093 (Entrez Gene)
ROCK2GeneProduct9475 (Entrez Gene)
Rac1GeneProduct5879 (Entrez Gene)
RhoAGeneProduct387 (Entrez Gene)
SOCSGeneProduct1154 (Entrez Gene)
STAT3GeneProduct6774 (Entrez Gene)
TAK1GeneProduct10454 (Entrez Gene)
TGF-betaGeneProduct7040 (Entrez Gene)
TNF-alphaGeneProduct7124 (Entrez Gene)
WNT3AGeneProduct89780 (Entrez Gene)
WNT5AGeneProduct7474 (Entrez Gene)
eIF2BεGeneProduct8893 (Entrez Gene)
gp130GeneProduct3572 (Entrez Gene)
hsa-let-7bRnaENSG00000207875 (Ensembl)
hsa-mir-103-1-asRnaENSG00000199035 (Ensembl)
hsa-mir-103-2-asRnaENSG00000199024 (Ensembl)
hsa-mir-125b-1RnaENSG00000207971 (Ensembl)
hsa-mir-125b-2RnaENSG00000207863 (Ensembl)
hsa-mir-130bRnaENSG00000207751 (Ensembl)
hsa-mir-133a-1RnaENSG00000276792 (Ensembl)
hsa-mir-133a-2RnaENSG00000207764 (Ensembl)
hsa-mir-133bRnaENSG00000199080 (Ensembl)
hsa-mir-140RnaENSG00000208017 (Ensembl)
hsa-mir-15bRnaENSG00000207779 (Ensembl)
hsa-mir-185RnaENSG00000208023 (Ensembl)
hsa-mir-195RnaENSG00000275739 (Ensembl)
hsa-mir-199a-1RnaENSG00000207752 (Ensembl)
hsa-mir-199a-2RnaENSG00000208024 (Ensembl)
hsa-mir-208aRnaENSG00000199157 (Ensembl)
hsa-mir-214RnaENSG00000207949 (Ensembl)
hsa-mir-21RnaENSG00000199004 (Ensembl)
hsa-mir-23aRnaENSG00000207980 (Ensembl)
hsa-mir-27bRnaENSG00000207864 (Ensembl)
hsa-mir-30eRnaENSG00000198974 (Ensembl)
mTORGeneProduct2475 (Entrez Gene)
p38GeneProduct1432 (Entrez Gene)

Annotated Interactions

No annotated interactions

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