Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT05619
[1]
m6A modification AC008 AC008 FTO Demethylation : m6A sites Direct Inhibition Non-coding RNA AC008 miR-328-3p  lncRNA       miRNA   circRNA
m6A Modification:
m6A Regulator Fat mass and obesity-associated protein (FTO) ERASER
m6A Target AC008440.5 (AC008)
Epigenetic Regulation that have Cross-talk with This m6A Modification:
Epigenetic Regulation Type Non-coding RNA (ncRNA)
Epigenetic Regulator AC008440.5 (AC008) LncRNA View Details
Regulated Target hsa-miR-328-3p View Details
Crosstalk Relationship m6A  →  ncRNA Inhibition
Crosstalk Mechanism m6A regulators directly modulate the functionality of ncRNAs through specific targeting ncRNA
Crosstalk Summary FTO-mediated N6-methyladenosine demethylation downregulated AC008440.5 (AC008) transcription, while lower FTO expression led to upregulation of AC008 transcription in OA. AC008 functioned as a competing endogenous RNA (ceRNA) to regulate hsa-miR-328-3p.
Responsed Disease Osteoarthritis ICD-11: FA05
Cell Process Cell apoptosis
In-vitro Model
Chondrocytes (Chondrocytes were isolated from human cartilage and cultured)
In-vivo Model 10-week-old male C57BL/6 mice were randomly divided into six groups: normal group (n = 5); MIA group (n = 5); MIA + agomir-NC group (n = 5); MIA + agomir-328-3p group (n = 5); MIA + AAV-NC group (n = 5); and MIA + AAV-AC008 group (n = 5). For induction of OA, mice were given an intra-articular injection of MIA (Sigma-Aldrich) in the knee. One week later, agomir-328-3p or negative control agomir (RiboBio) and adeno-associated virus expressing AC008 (AAV-AC008) or negative control virus (GeneChem, Shanghai, China) were injected into the knee joints of mice in the appropriate groups. Treatments were administered at 20 μL per joint per mouse once per week for 5 consecutive weeks. Six weeks later, the mice were euthanized, and the knee joints were collected for safranin-O/fast green staining and IHC analysis.
References
Ref 1 m(6)A-mediated upregulation of AC008 promotes osteoarthritis progression through the miR-328-3p?AQP1/ANKH axis. Exp Mol Med. 2021 Nov;53(11):1723-1734. doi: 10.1038/s12276-021-00696-7. Epub 2021 Nov 4.