MicroRNAs in cardiomyocyte hypertrophy (Homo sapiens)

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217213822111188871111211116RTKsSarcomere organizationGPCRStressProtein SynthesisPI3KStressGαq/α11StretchGC-ATranscription FactorsRASRhoTNFRHypertrophic gene transcriptionCatecholaminesGβγTGFR/ActivinNucleusCelmembraneGPCRPol IICellular ProteinsRCAN1 promotorNFκBhsa-mir-23aPIK3CBp38hsa-mir-125b-2MLCK1FZD2hsa-mir-199a-2hsa-mir-27bTNFαhsa-mir-27bLRP5hsa-mir-140hsa-mir-21hsa-mir-103-2-asNFAT3hsa-mir-21hsa-mir-199a-2EGFhsa-mir-23ahsa-mir-199a-2hsa-mir-15bRAF1hsa-mir-199a-1MEK1hsa-mir-133a-1hsa-mir-199a-1CalciumERK1hsa-mir-30ehsa-let-7bhsa-mir-15bMEK2JNKMAPKKKhsa-mir-30ehsa-mir-23ahsa-mir-133bCalmodulinhsa-mir-199a-2CalNARhoAhsa-mir-27bHDAC 4hsa-mir-185ANPTGFβhsa-mir-27bhsa-mir-125b-2PDKMEK4WNT3AMAPKKKhsa-mir-199a-1hsa-mir-15bhsa-mir-27bhsa-mir-21Calmodulinhsa-mir-23aNFAT3gp130MEK6hsa-mir-15bhsa-mir-30ehsa-mir-185hsa-mir-15bhsa-mir-195hsa-mir-23aDAGhsa-mir-133a-2hsa-mir-23aPKCβhsa-mir-133bET-1HDAC 4hsa-mir-27bhsa-mir-140IKKahsa-mir-15bLIFMAPKKKCT-1hsa-mir-195hsa-mir-133a-2hsa-mir-195hsa-mir-195AKT2IKKbhsa-mir-195CalciumPIK3CDFGF2PLChsa-mir-125b-1eIF2BεPIK3R3HDAC 7hsa-mir-208ahsa-mir-27bhsa-mir-195PIK3R2hsa-mir-199a-1PIK3R1hsa-mir-130bhsa-mir-125b-1BNPERK1MEK3hsa-mir-30ehsa-mir-133a-2MEK7AKT1IκBTAK1NFAT3ERK5SOCSAng IIhsa-mir-15bhsa-let-7bhsa-mir-133bGSK3βhsa-mir-199a-2ROCK2hsa-let-7bCyclic GMPPLA2hsa-mir-15bCamKNFκBhsa-mir-195WNT5AFGFR2MEK5IKKgHDAC 5hsa-mir-130bHDAC 5HDAC 7hsa-mir-103-1-asGSK3βIP3CDK 9PIK3CGNeuregulinPIK3CAhsa-mir-199a-2hsa-mir-27bhsa-mir-23ap38Dvl1hsa-mir-15bhsa-mir-125b-1hsa-mir-199a-1CDK 7MEF-2IGF-1 Rhsa-mir-103-1-ashsa-mir-15bCalNBSTAT3hsa-mir-15bhsa-mir-30ehsa-mir-195CalciumRCAN1STAT3PKG Ihsa-mir-199a-1GATA4hsa-mir-199a-1hsa-mir-30ehsa-mir-125b-1hsa-mir-133a-1ROCK1PKCβhsa-mir-125b-2hsa-mir-195hsa-mir-140Rac1hsa-mir-195hsa-mir-133a-1PDK1hsa-let-7bLRP6hsa-let-7bJNKhsa-mir-27bmTORhsa-mir-125b-2β-cateninHDAC 9IGFIhsa-let-7bNIKhsa-mir-195ERK2hsa-mir-30eFZD1MAPKKKKhsa-mir-103-2-asHDAC 9ERK2hsa-mir-30eMLCK3GeneProducthsa-mir-199a-2Ang II


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 pink. 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. 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 Europe PMC
  2. 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 Europe PMC
  3. Molkentin JD; ''Calcineurin and beyond: cardiac hypertrophic signaling.''; Circ Res, 2000 PubMed Europe PMC
  4. Heineke J, Molkentin JD; ''Regulation of cardiac hypertrophy by intracellular signalling pathways.''; Nat Rev Mol Cell Biol, 2006 PubMed Europe PMC
  5. 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 Europe PMC
  6. Lim HW, Molkentin JD; ''Calcineurin and human heart failure.''; Nat Med, 1999 PubMed Europe PMC
  7. 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 Europe PMC
  8. 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 Europe PMC
  9. 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 Europe PMC
  10. Olson EN, Molkentin JD; ''Prevention of cardiac hypertrophy by calcineurin inhibition: hope or hype?''; Circ Res, 1999 PubMed Europe PMC
  11. 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 Europe PMC
  12. 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 Europe PMC
  13. Wollert KC, Chien KR; ''Cardiotrophin-1 and the role of gp130-dependent signaling pathways in cardiac growth and development.''; J Mol Med, 1997 PubMed Europe PMC
  14. Haghikia A, Stapel B, Hoch M, Hilfiker-Kleiner D; ''STAT3 and cardiac remodeling.''; Heart Fail Rev, 2010 PubMed Europe PMC
  15. Clerk A, Sugden PH; ''Small guanine nucleotide-binding proteins and myocardial hypertrophy.''; Circ Res, 2000 PubMed Europe PMC
  16. 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 Europe PMC
  17. Vanhaesebroeck B, Alessi DR; ''The PI3K-PDK1 connection: more than just a road to PKB.''; Biochem J, 2000 PubMed Europe PMC


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106646view21:07, 12 September 2019KhanspersModified description
106194view12:09, 16 August 2019MaintBotHMDB identifier normalization
105649view05:11, 10 August 2019KhanspersModified description
104849view14:44, 20 June 2019Fehrhartgraphical line between PI3K and complex
104848view14:39, 20 June 2019Fehrhart
102988view13:20, 31 January 2019SusanUpdated microRNA genes from RNA to GeneProduct
102987view13:06, 31 January 2019SusanRe-annotated microRNAs
98337view13:27, 23 August 2018EgonwUpdated the MIR21 identifier.
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

External references


View all...
NameTypeDatabase referenceComment
AKT1GeneProduct207 (Entrez Gene)
AKT2GeneProduct208 (Entrez Gene)
ANPGeneProduct4878 (Entrez Gene)
Ang IIGeneProduct183 (Entrez Gene)
BNPGeneProduct4879 (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)
GSK3βGeneProduct2932 (Entrez Gene)
HDAC 4GeneProduct9759 (Entrez Gene)
HDAC 5GeneProduct10014 (Entrez Gene)
HDAC 7GeneProduct51564 (Entrez Gene)
HDAC 9GeneProduct9734 (Entrez Gene)
IGF-1 RGeneProduct3480 (Entrez Gene)
IGFIGeneProduct3479 (Entrez Gene)
IKKaGeneProduct1147 (Entrez Gene)
IKKbGeneProduct3551 (Entrez Gene)
IKKgGeneProduct8517 (Entrez Gene)
IP3MetaboliteHMDB01498 (HMDB)
IκBGeneProduct9641 (Entrez Gene)
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)
NFAT3GeneProduct4776 (Entrez Gene)
NFκBGeneProduct4790 (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)
PKCβGeneProduct5579 (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)
TGFβGeneProduct7040 (Entrez Gene)
TNFαGeneProduct7124 (Entrez Gene)
WNT3AGeneProduct89780 (Entrez Gene)
WNT5AGeneProduct7474 (Entrez Gene)
eIF2BεGeneProduct8893 (Entrez Gene)
gp130GeneProduct3572 (Entrez Gene)
hsa-let-7bRnaENSG00000207875 (Ensembl Human)
hsa-mir-103-1-asRnaENSG00000199035 (Ensembl Human)
hsa-mir-103-2-asRnaENSG00000199024 (Ensembl Human)
hsa-mir-125b-1RnaENSG00000207971 (Ensembl Human)
hsa-mir-125b-2RnaENSG00000207863 (Ensembl Human)
hsa-mir-130bRnaENSG00000207751 (Ensembl Human)
hsa-mir-133a-1RnaENSG00000207786 (Ensembl Human)
hsa-mir-133a-2RnaENSG00000207764 (Ensembl Human)
hsa-mir-133bRnaENSG00000199080 (Ensembl Human)
hsa-mir-140RnaENSG00000208017 (Ensembl Human)
hsa-mir-15bRnaENSG00000207779 (Ensembl Human)
hsa-mir-185RnaENSG00000208023 (Ensembl Human)
hsa-mir-195RnaENSG00000207929 (Ensembl Human)
hsa-mir-199a-1RnaENSG00000207752 (Ensembl Human)
hsa-mir-199a-2RnaENSG00000208024 (Ensembl Human)
hsa-mir-208aRnaENSG00000199157 (Ensembl Human)
hsa-mir-21RnaENSG00000199004 (Ensembl Human)
hsa-mir-23aRnaENSG00000207980 (Ensembl Human)
hsa-mir-27bRnaENSG00000207864 (Ensembl Human)
hsa-mir-30eRnaENSG00000198974 (Ensembl Human)
mTORGeneProduct2475 (Entrez Gene)
p38GeneProduct1432 (Entrez Gene)
β-cateninGeneProduct1499 (Entrez Gene)

Annotated Interactions

No annotated interactions

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