Table 3 Predicted pathways and genes affected by aberrantly expressed miRNAs in TLE with onset in adulthood and infancy.

From: Dynamic miRNA changes during the process of epileptogenesis in an infantile and adult-onset model

 

Pathway

miRNAs involved

Genes affected

Predicted targets in infantile-onset epilepsy

Acute

TGF-β signalling

miR-205, -330-3p,-3473, -7a-2-3p

Smad1

SMAD family member 1

Smad5

SMAD family member 5

Smad7

SMAD family member 7

Bambi

BMP and activin membrane-bound inhibitor

Id2

Inhibitor of DNA binding 2, HLH protein

Zfyve16

Zinc finger FYVE-type containing protein 16

Ppp2ca

Serine/threonine-protein phosphatase 2CA catalytic subunit alpha isoform

Acvr1

Activin A receptor type 1

Smurf2

SMAD specific E3 ubiquitin protein ligase 2

Morphine addiction

miR-205, -221-3p, -330-3p

Gabra1

Gamma-aminobutyric acid type A receptor gamma 1 subunit

Gnb3

Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-3

Pde3b

Phosphodiesterase 3B

Long-term depression

miR-205, -221-3p, -330-3p,-7a-2-3p

Gnai2

Guanine nucleotide-binding protein G(s) subunit alpha

Itpr2

Inositol 1,4,5-trisphosphate receptor, type 1

Ppp2ca

Serine/threonine-protein phosphatase 2CA catalytic subunit alpha isoform

Hippo signalling

miR-205, -221-3p, -330-3p,-7a-2-3p

Smad1

SMAD family member 1

Smad7

SMAD family member 7

Ppp2ca

Serine/threonine-protein phosphatase 2CA catalytic subunit alpha isoform

Ywhag

Tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, eta

Id2

Inhibitor of DNA binding 2, HLH protein

Prkci

Protein kinase C, iota

Axin2

Axin 2

Tef7l2

Lymphoid enhancer binding factor 2

Dlg2

Discs large MAGUK scaffold protein 1

Wnt signalling

miR-205, -221-3p, -330-3p,-6215, -7a-2-3p

Bambi

BMP and activin membrane-bound inhibitor

Tbl1xr1

Transducin (beta)-like 1 X-linked

Nfatc3

Nuclear factor of activated T-cells 3

Ppp3r1

Protein phosphatase 3, regulatory subunit B, alpha

Prickle2

Prickle planar cell polarity protein 2

Cxxc4

CXXC finger protein 4

Axin2

Axin 2

Siaha

Siah E3 ubiquitin protein ligase 1

Sox17

Transcription factor SOX17

Tef7l2

Lymphoid enhancer binding factor 2

Nlk

Nemo like kinase

Glutamatergic synapse

miR-205, -221-3p, -330-3p,-6215

Gnb3

Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-3

Gnai2

G protein subunit alpha i2

Ppp3r1

Protein phosphatase 3, regulatory subunit B, alpha

Itpr2

Inositol 1,4,5-trisphosphate receptor, type 1

Homer2

Homer scaffolding protein 1

GABAergic synapse

miR -205, -221-3p, -330-3p

Gabra1

Gamma-aminobutyric acid type A receptor gamma 1 subunit

Gnb3

Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-3

Trak2

Trafficking kinesin protein 2

Chronic

Pentose phosphate pathway

miR-451-5p

Prps2

Phosphoribosyl pyrophosphate synthetase 2

Glutamate metabolism

miR-451-5p

Gfpt2

Glutamine fructose-6-phosphate transaminase 2

Sugar metabolism

miR-451-5p

Gfpt2

Glutamine fructose-6-phosphate transaminase 2

Biosynthesis of amino acids

miR-451-5p

Prps2

Phosphoribosyl pyrophosphate synthetase 2

Carbon metabolism

miR-451-5p

Prps2

Phosphoribosyl pyrophosphate synthetase 2

Predicted targets in adult-onset epilepsy

Acute

MAPK signalling

miR-132-3p, -142-3p, -142-5p, -155-5p, -212-3p, -361-3p

Cacnb4

Calcium voltage-gated channel auxiliary subunit beta 4

DUSP2 And 9

Dual specificity phosphatase 2 and 9

Fgf14

Fibroblast growth factor 4

Il1a

Interleukin 1 alpha

MAP3K3, 6 And 14

Mitogen activated protein kinase 3, 6 and 14

Mapkapk2

Mitogen-activated protein kinase-activated protein kinase 2

Mecom

Ecotropic virus integration site 1 protein

Nlk

nemo like kinase

Ptpn5

Protein tyrosine phosphatase, non-receptor type 5

Rap1b

Ras-related protein Rap-1B

Rasa1

RAS P21 Protein Activator 1

Rasgrf1

RAS protein-specific guanine nucleotide-releasing factor 2

Rela

RELA proto-oncogene, NF-kB subunit

RPS6KA3 And 4

Ribosomal protein S6 kinase A3 and 4

RRAS Adn 2

Ras-related protein R-Ras

Sos1

SOS Ras/Rac guanine nucleotide exchange factor 1

Srf

Serum response factor

Tab2

TGF-beta activated kinase 1/MAP3K7 binding protein 2

Tgfbr1

Transforming growth factor, beta receptor 1

Ras signalling

miR-132-3p, -142-3p, -142-5p, -155-5p, -212-3p, -361-3p

Bcl2l1

Bcl-2-like 1 (apoptosis regulator Bcl-X)

Csf1r

Colony stimulating factor 1 receptor

ETS1 And 2

ETS proto-oncogene 1 and 2, transcription factor

Foxo4

Forkhead box protein O4

Gab1

GRB2-associated binding protein 1

Grin2a

Glutamate Ionotropic Receptor NMDA Type Subunit 2A

Kitlg

KIT ligand

Rap1b

Ras-related protein Rap-1B

Rasa1

RAS P21 Protein Activator 1

Rasgrf1

RAS protein-specific guanine nucleotide-releasing factor 1

Rela

RELA proto-oncogene, NF-kB subunit

Rgl2

Ral guanine nucleotide dissociation stimulator-like 2

RRAS And 2

Ras-related protein R-Ras

Latent

Mucin type O-glycan biosynthesis

miR-185-5p, -7b

Galnt3

Polypeptide N-acetylgalactosaminyltransferase3

Galnt5

Polypeptide N-acetylgalactosaminyltransferase5

Synaptic vesicle cycle

miR-185-5p, -7b

Syt1

Synaptotagmin 1, isoform A

Snap25

Synaptosomal-associated protein 25

Slc18a2

Solute carrier family 18 member 2

Atp6v1e1

ATPase H + transporting V1 subunit E1

Chronic

Amphetamine addiction

miR-142-5p,-146a-5p, -221-3p

Ddc

Dopa decarboxylase

Fos

FBJ osteosarcoma oncogene

Ppp3r1

Protein phosphatase 3, regulatory subunit B, alpha

Slc18a2

Solute carrier family 18 (vesicular amine transporter), member 2

Cocaine addiction

miR-142-5p,-146a-5p, -221-3p

Dlg4

Discs large MAGUK scaffold protein 4

Gnai2

G protein subunit alpha i2

Ddc

Dopa decarboxylase

Nfkb1

Nuclear Factor Kappa B Subunit 1

Slc18a2

Solute carrier family 18 (vesicular amine transporter), member 2

GABAergic synapse

miR-146a-5p, -205, -221-3p

Gabra1

Gamma-aminobutyric acid type A receptor gamma 1 subunit

Gnb3

Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-3

Trak2

Trafficking kinesin protein 2

Scl38a5

Solute carrier family 38 (sodium-coupled neutral amino acid transporter), member 5

Hippo signalling

miR-205, -221-3p, -330-3p,-142-5p, -146a-5p

Smad1

SMAD family member 1

Smad4

SMAD family member 4

Smad7

SMAD family member 7

Ywhag

Tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, eta

Id2

Inhibitor of DNA binding 2, HLH protein

Axin2

Axin 2

Tef7l2

Lymphoid enhancer binding factor 1

DLG2 And 4

Discs large MAGUK scaffold protein 2 and 4

Morphine addiction

miR-142-5p, -205, -221-3p

Gabra1

Gamma-aminobutyric acid type A receptor gamma 1 subunit

Gnb3

Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-3

Pde3b

Phosphodiesterase 3B

NF-κB signalling

miR-146a-5p, -221-3p

Traf6

TNF receptor associated factor 6

Map3k14

Mitogen-activated protein kinase kinase 14

Nfkb1

Nuclear Factor Kappa B Subunit 1

Irak1

Interleukin-1 receptor-associated kinase 4

TGF-β signalling

miR-205, -142-5p, -146a-5p

Smad1

SMAD family member 1

Smad4

SMAD family member 4

Smad7

SMAD family member 7

Bambi

BMP and activin membrane-bound inhibitor

Id2

Inhibitor of DNA binding 2, HLH protein

Zfyve16

Zinc finger FYVE-type containing protein 16

Ubiquitin mediated proteolysis

miR-205, -221-3p,-142-5p, -146a-5p

Herc3

E3 ubiquitin-protein ligase HERC3

Mgrn1

E3 ubiquitin-protein ligase MGRN1

Siah1a

Siah E3 ubiquitin protein ligase 1

Traf6

TNF receptor associated factor 6

UBE2a,2e3,3A, 4A

Ubiquitin-conjugating enzyme E2A, 2E3, 3A, 4A

Uba 6

Ubiquitin-like modifier activating enzyme 6

Wwp1

WW domain containing E3 ubiquitin protein ligase 1

Wnt signalling

miR-205, -221-3p, -330-3p,-6215, -7a-2-3p

Bambi

BMP and activin membrane-bound inhibitor

Tbl1xr1

Transducin (beta)-like 1 X-linked

Nfatc3

Nuclear factor of activated T-cells 3

Ppp3r1

Protein phosphatase 3, regulatory subunit B, alpha

Cxxc4

CXXC finger protein 4

Axin2

Axin 2

Siah1a

Siah E3 ubiquitin protein ligase 1

Nlk

Nemo like kinase

Vangl1

VANGL planar cell polarity protein 2

Fzd1

Frizzled 1/7

  1. Detailed list of predicted pathways and genes regulated by miRNAs with altered expression across three epilepsy stages in TLE model. DIANA mirPath v3 software generated predicted pathways based on miRNA lists uploaded for each epilepsy stage with both onset groups analysed separately. Bold font marks the miRNAs and their targets validated in rat included in miRTarbase database.