General Information of the Disease (ID: M6ADIS0092)
Name
Muscular dystrophies
ICD
ICD-11: 8C70
Full List of Target Gene(s) of This m6A-centered Disease Response
Ephrin type-B receptor 2 (ERK/EPHB2)
In total 3 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [1]
Response Summary m6A writers METTL3/METTL14 and the m6A reader YTHDF1 orchestrate MNK2 expression posttranscriptionally and thus control Ephrin type-B receptor 2 (ERK/EPHB2) signaling, which is required for the maintenance of muscle myogenesis and contributes to regeneration.
Responsed Disease Muscular dystrophies [ICD-11: 8C70]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
Target Regulation Up regulation
Pathway Response MAPK signaling pathway hsa04010
In-vitro Model HEK293T Normal Homo sapiens CVCL_0063
C2C12 Normal Mus musculus CVCL_0188
In-vivo Model For mouse muscle injury and regeneration experiment, tibialis anterior (TA) muscles of 6-week-old male mice were injected with 25 uL of 10 uM cardiotoxin (CTX, Merck Millipore, 217503), 0.9% normal saline (Saline) were used as control. The regenerated muscles were collected at day 1, 3, 5, and 10 post-injection. TA muscles were isolated for Hematoxylin and eosin staining or frozen in liquid nitrogen for RNA and protein extraction.
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene [1]
Response Summary m6A writers METTL3/METTL14 and the m6A reader YTHDF1 orchestrate MNK2 expression posttranscriptionally and thus control Ephrin type-B receptor 2 (ERK/EPHB2) signaling, which is required for the maintenance of muscle myogenesis and contributes to regeneration.
Responsed Disease Muscular dystrophies [ICD-11: 8C70]
Target Regulator Methyltransferase-like 14 (METTL14) WRITER
Target Regulation Up regulation
Pathway Response MAPK signaling pathway hsa04010
In-vitro Model HEK293T Normal Homo sapiens CVCL_0063
C2C12 Normal Mus musculus CVCL_0188
In-vivo Model For mouse muscle injury and regeneration experiment, tibialis anterior (TA) muscles of 6-week-old male mice were injected with 25 uL of 10 uM cardiotoxin (CTX, Merck Millipore, 217503), 0.9% normal saline (Saline) were used as control. The regenerated muscles were collected at day 1, 3, 5, and 10 post-injection. TA muscles were isolated for Hematoxylin and eosin staining or frozen in liquid nitrogen for RNA and protein extraction.
Experiment 3 Reporting the m6A-centered Disease Response by This Target Gene [1]
Response Summary m6A writers METTL3/METTL14 and the m6A reader YTHDF1 orchestrate MNK2 expression posttranscriptionally and thus control Ephrin type-B receptor 2 (ERK/EPHB2) signaling, which is required for the maintenance of muscle myogenesis and contribute to regeneration.
Responsed Disease Muscular dystrophies [ICD-11: 8C70]
Target Regulator YTH domain-containing family protein 1 (YTHDF1) READER
Target Regulation Up regulation
Pathway Response MAPK signaling pathway hsa04010
In-vitro Model HEK293T Normal Homo sapiens CVCL_0063
C2C12 Normal Mus musculus CVCL_0188
In-vivo Model For mouse muscle injury and regeneration experiment, tibialis anterior (TA) muscles of 6-week-old male mice were injected with 25 uL of 10 uM cardiotoxin (CTX, Merck Millipore, 217503), 0.9% normal saline (Saline) were used as control. The regenerated muscles were collected at day 1, 3, 5, and 10 post-injection. TA muscles were isolated for Hematoxylin and eosin staining or frozen in liquid nitrogen for RNA and protein extraction.
MAP kinase signal-integrating kinase 2 (MNK2)
In total 3 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [1]
Response Summary m6A writers METTL3/METTL14 and the m6A reader YTHDF1 orchestrate MAP kinase signal-integrating kinase 2 (MNK2) expression posttranscriptionally and thus control ERK signaling, which is required for the maintenance of muscle myogenesis and contributes to regeneration.
Responsed Disease Muscular dystrophies [ICD-11: 8C70]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
Target Regulation Up regulation
Pathway Response MAPK signaling pathway hsa04010
In-vitro Model HEK293T Normal Homo sapiens CVCL_0063
C2C12 Normal Mus musculus CVCL_0188
In-vivo Model For mouse muscle injury and regeneration experiment, tibialis anterior (TA) muscles of 6-week-old male mice were injected with 25 uL of 10 uM cardiotoxin (CTX, Merck Millipore, 217503), 0.9% normal saline (Saline) were used as control. The regenerated muscles were collected at day 1, 3, 5, and 10 post-injection. TA muscles were isolated for Hematoxylin and eosin staining or frozen in liquid nitrogen for RNA and protein extraction.
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene [1]
Response Summary m6A writers METTL3/METTL14 and the m6A reader YTHDF1 orchestrate MAP kinase signal-integrating kinase 2 (MNK2) expression posttranscriptionally and thus control ERK signaling, which is required for the maintenance of muscle myogenesis and contributes to regeneration.
Responsed Disease Muscular dystrophies [ICD-11: 8C70]
Target Regulator Methyltransferase-like 14 (METTL14) WRITER
Target Regulation Up regulation
Pathway Response MAPK signaling pathway hsa04010
In-vitro Model HEK293T Normal Homo sapiens CVCL_0063
C2C12 Normal Mus musculus CVCL_0188
In-vivo Model For mouse muscle injury and regeneration experiment, tibialis anterior (TA) muscles of 6-week-old male mice were injected with 25 uL of 10 uM cardiotoxin (CTX, Merck Millipore, 217503), 0.9% normal saline (Saline) were used as control. The regenerated muscles were collected at day 1, 3, 5, and 10 post-injection. TA muscles were isolated for Hematoxylin and eosin staining or frozen in liquid nitrogen for RNA and protein extraction.
Experiment 3 Reporting the m6A-centered Disease Response by This Target Gene [1]
Response Summary m6A writers METTL3/METTL14 and the m6A reader YTHDF1 orchestrate MAP kinase signal-integrating kinase 2 (MNK2) expression posttranscriptionally and thus control ERK signaling, which is required for the maintenance of muscle myogenesis contributes to regeneration.
Responsed Disease Muscular dystrophies [ICD-11: 8C70]
Target Regulator YTH domain-containing family protein 1 (YTHDF1) READER
Target Regulation Up regulation
Pathway Response MAPK signaling pathway hsa04010
In-vitro Model HEK293T Normal Homo sapiens CVCL_0063
C2C12 Normal Mus musculus CVCL_0188
In-vivo Model For mouse muscle injury and regeneration experiment, tibialis anterior (TA) muscles of 6-week-old male mice were injected with 25 uL of 10 uM cardiotoxin (CTX, Merck Millipore, 217503), 0.9% normal saline (Saline) were used as control. The regenerated muscles were collected at day 1, 3, 5, and 10 post-injection. TA muscles were isolated for Hematoxylin and eosin staining or frozen in liquid nitrogen for RNA and protein extraction.
Negative growth regulatory protein MyD118 (GADD45B)
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [2]
Response Summary Negative growth regulatory protein MyD118 (GADD45B)-mediated m6A modification in Negative growth regulatory protein MyD118 (GADD45B) mRNA drives skeletal muscle differentiation by activating the p38 MAPK pathway, which provides a molecular mechanism for the regulation of myogenesis via RNA methylation.
Responsed Disease Muscular dystrophies [ICD-11: 8C70]
Target Regulator Fat mass and obesity-associated protein (FTO) ERASER
Target Regulation Up regulation
Pathway Response Nucleotide excision repair hsa03420
MAPK signaling pathway hsa04010
Cell Process DNA repair
In-vitro Model GPM (Goat primary myoblasts)
In-vivo Model Sixteen female goats in good body condition and suitable for pregnancy were selected. All selected goats underwent estrus synchronization treatment and were naturally mated. After 75 days of gestation, four male fetuses were removed from five pregnant goats during abortion operations, and their longissimus muscle samples were collected.
PPAR-gamma coactivator 1-alpha (PGC-1a/PPARGC1A)
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [3]
Response Summary FTO downregulation suppressed mitochondria biogenesis and energy production, showing as the decreased mitochondria mass and mitochondrial DNA (mtDNA) content, the downregulated expression of mtDNA-encoding genes and PPAR-gamma coactivator 1-alpha (PGC-1a/PPARGC1A) gene, together with declined ATP level. These findings provide the first evidence for the contribution of FTO for skeletal muscle differentiation.
Responsed Disease Muscular dystrophies [ICD-11: 8C70]
Target Regulator Fat mass and obesity-associated protein (FTO) ERASER
Target Regulation Up regulation
Cell Process Myogenic differentiation
mTOR signaling pathway (hsa04150)
In-vitro Model MPM (Mouse primary myoblasts from about 10-day-old C57BL/6J were isolated)
C2C12 Normal Mus musculus CVCL_0188
HEK293-FT Normal Homo sapiens CVCL_6911
In-vivo Model To generate doxycycline-inducible skeletal muscle-specific FTO deletion mice, FTOflox/flox mice were crossed with HSA-Cre mice to generate FTOflox/+ HSA-Cre mice, which were then crossed to FTOflox/flox mice to generate FTOflox/flox and FTOflox/flox HSA-Cre mice.
References
Ref 1 Dynamic m(6)A mRNA Methylation Reveals the Role of METTL3/14-m(6)A-MNK2-ERK Signaling Axis in Skeletal Muscle Differentiation and Regeneration. Front Cell Dev Biol. 2021 Oct 1;9:744171. doi: 10.3389/fcell.2021.744171. eCollection 2021.
Ref 2 FTO-mediated demethylation of GADD45B promotes myogenesis through the activation of p38 MAPK pathway. Mol Ther Nucleic Acids. 2021 Jun 24;26:34-48. doi: 10.1016/j.omtn.2021.06.013. eCollection 2021 Dec 3.
Ref 3 FTO is required for myogenesis by positively regulating mTOR-PGC-1Alpha pathway-mediated mitochondria biogenesis. Cell Death Dis. 2017 Mar 23;8(3):e2702. doi: 10.1038/cddis.2017.122.