General Information of the Disease (ID: M6ADIS0102)
Name
Aortic aneurysm or dissection
ICD
ICD-11: BD50
Full List of Target Gene(s) of This m6A-centered Disease Response
Glycogen synthase kinase-3 beta (GSK3Beta/GSK3B)
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [1]
Response Summary FTO expression significantly contributes to the phenotype conversion of VSMCs and the aortic dissecting aneurysm by the demethylation function (m6A), thereby providing a novel therapeutic target. Knockdown of FTO suppresses the Glycogen synthase kinase-3 beta (GSK3Beta/GSK3B) levels and Klf5 expression regardless of AngII treatment.
Responsed Disease Aortic aneurysm or dissection [ICD-11: BD50]
Target Regulator Fat mass and obesity-associated protein (FTO) ERASER
Target Regulation Up regulation
Pathway Response Nucleotide excision repair hsa03420
Cell Process DNA repair
Cell proliferation and migration
In-vitro Model VSMC (Human aortic vascular smooth muscle cells)
Krueppel-like factor 5 (KLF5)
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [1]
Response Summary FTO expression significantly contributes to the phenotype conversion of VSMCs and the aortic dissecting aneurysm by the demethylation function (m6A), thereby providing a novel therapeutic target. Knockdown of FTO suppresses the p-GSK3-beta levels and Krueppel-like factor 5 (KLF5) expression regardless of AngII treatment.
Responsed Disease Aortic aneurysm or dissection [ICD-11: BD50]
Target Regulator Fat mass and obesity-associated protein (FTO) ERASER
Target Regulation Up regulation
Pathway Response Nucleotide excision repair hsa03420
Cell Process DNA repair
Cell proliferation and migration
In-vitro Model VSMC (Human aortic vascular smooth muscle cells)
hsa-miR-143-3p
In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [2]
Response Summary KIAA1429 is downregulated while ALKBH5 is upregulated in aortic tissues from aortic dissection patients. KIAA1429/ALKBH5-mediated m6A modifications can regulate the processing of hsa-miR-143-3p through interacting with the microprocessor protein DGCR8. KIAA1429 and ALKBH5 can oppositely regulate HASMC proliferation, HAEC apoptosis, and AD progression in AngII-infused mice via the miR-143-3p/DDX6 pathway.
Responsed Disease Aortic aneurysm or dissection [ICD-11: BD50]
Target Regulator Protein virilizer homolog (VIRMA) WRITER
Target Regulation Down regulation
Pathway Response RNA degradation hsa03018
Cell Process Cell apoptosis
In-vitro Model IM-HAEC Normal Homo sapiens CVCL_B5WL
In-vivo Model Osmotic mini-pumps containing AngII (1 ug/kg/min, Enzo Bioche) were implanted in 7-week-old male mice. To interfere with the expression of KIAA1429, ALKBH5, or DDX6 in vivo, adeno-associated virus 9 (AAV9) vectors carrying a variety of overexpression plasmids or interfering RNA were randomly injected through the tail vein to C57BL/6N mice.
Experiment 2 Reporting the m6A-centered Disease Response by This Target Gene [2]
Response Summary KIAA1429 is downregulated while ALKBH5 is upregulated in aortic tissues from aortic dissection patients. KIAA1429/ALKBH5-mediated m6A modifications can regulate the processing of hsa-miR-143-3p through interacting with the microprocessor protein DGCR8. KIAA1429 and ALKBH5 can oppositely regulate HASMC proliferation, HAEC apoptosis, and AD progression in AngII-infused mice via the miR-143-3p/DDX6 pathway.
Responsed Disease Aortic aneurysm or dissection [ICD-11: BD50]
Target Regulator RNA demethylase ALKBH5 (ALKBH5) ERASER
Target Regulation Down regulation
Pathway Response RNA degradation hsa03018
Cell Process Cell apoptosis
In-vitro Model IM-HAEC Normal Homo sapiens CVCL_B5WL
In-vivo Model Osmotic mini-pumps containing AngII (1 ug/kg/min, Enzo Bioche) were implanted in 7-week-old male mice. To interfere with the expression of KIAA1429, ALKBH5, or DDX6 in vivo, adeno-associated virus 9 (AAV9) vectors carrying a variety of overexpression plasmids or interfering RNA were randomly injected through the tail vein to C57BL/6N mice.
hsa-miR-34a
In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene [3]
Response Summary METTL3/m6A-mediated hsa-miR-34a maturation in AAA formation and provide a novel therapeutic target and diagnostic biomarker for AAA treatment.
Responsed Disease Abdominal aortic aneurysm [ICD-11: BD50.4]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
Target Regulation Up regulation
In-vitro Model VSMC (Human aortic vascular smooth muscle cells)
In-vivo Model Male C57BL/6J mice were anesthetized with an intraperitoneal injection of pentobarbital (40 mg/kg). The abdominal aorta between the renal arteries and the bifurcation of the iliac arteries was disassociated from the surrounding structures. Video microscopy was used to assay the diameter of the aorta in triplicate. After the measurements were taken, a small piece of gauze dipped in 0.5 mol/L CaCl2 was spread perivascularly onto the aortic passage for 15 min. Control mice received substitute treatment with NaCl (0.9%)-soaked gauze for 15 min. Then, the aorta was rinsed with 0.9% sterile saline, and the incision was sutured. After 3 or 6 weeks, all the animals were sacrificed, and the aortas were harvested for further analysis.
References
Ref 1 Vascular Smooth Muscle FTO Promotes Aortic Dissecting Aneurysms via m6A Modification of Klf5. Front Cardiovasc Med. 2020 Nov 20;7:592550. doi: 10.3389/fcvm.2020.592550. eCollection 2020.
Ref 2 KIAA1429 and ALKBH5 Oppositely Influence Aortic Dissection Progression via Regulating the Maturation of Pri-miR-143-3p in an m6A-Dependent Manner. Front Cell Dev Biol. 2021 Aug 19;9:668377. doi: 10.3389/fcell.2021.668377. eCollection 2021.
Ref 3 METTL3 Induces AAA Development and Progression by Modulating N6-Methyladenosine-Dependent Primary miR34a Processing. Mol Ther Nucleic Acids. 2020 Sep 4;21:394-411. doi: 10.1016/j.omtn.2020.06.005. Epub 2020 Jun 10.