m6A-centered Crosstalk Information

Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT05658
 [1]
m6A modification Circ_SETD2 Circ_SETD2 FTO Demethylation : m6A sites Direct Inhibition Non-coding RNA circSETD2 miR-181a-5p  lncRNA       miRNA   circRNA
m6A Modification:
m6A Regulator Fat mass and obesity-associated protein (FTO) ERASER
 Regulator Info 
m6A Target Circ_SETD2
 Targert Gene 
Epigenetic Regulation that have Cross-talk with This m6A Modification:
Epigenetic Regulation Type Non-coding RNA (ncRNA)
Epigenetic Regulator Circ_SETD2 circRNA View Details
Regulated Target hsa-miR-181a-5p View Details
Crosstalk Relationship m6A  →  ncRNA Inhibition
Crosstalk Mechanism m6A regulators directly modulate the functionality of ncRNAs through specific targeting ncRNA
Crosstalk Summary Knockdown of FTO increased total m6A, Circ_SETD2 m6A, and circSETD2 levels. m6A modification mediated circSETD2 upregulation. circSETD2 was a sponge of hsa-miR-181a-5p to elevate MCL1 transcription. miR-181a-5p overexpression or MCL1 silencing annulled the role of m6A-modified circSETD2. circSETD2 inhibition negated suppression of METTL3 overexpression on chorionic trophoblast apoptosis in vivo. Collectively, m6A modification of circSETD2 suppressed miR-181a-5p and increased MCL1 transcription, thus regulating trophoblasts.
Responsed Disease Pre-eclampsia ICD-11: JA24
 Disease Info 
Cell Process Cell proliferation
Cell invasion
Cell apoptosis
In-vitro Model
 HTR-8/SVneo Normal Homo sapiens CVCL_7162
In-vivo Model Pregnant rats were randomly assigned to 5 groups: normal pregnancy (normal) group, PE group, circSETD2 overexpression (PE + oe-circSETD2) group, METTL3 overexpression (PE + oe-METTL3) group, overexpression control (PE + oe-NC) group, joint treatment (PE + oe-METTL3 + si-circSETD2) group, and joint treatment control (PE + oe-METTL3 + si-NC) group, with 6 rats in each group. After continuous injection of L-NAME for 4 days, the rats in the overexpression and overexpression control groups were further injected with 30 μl lentivirus vector oe-circSETD2, oe-METTL3 or oe-NC solution (GenePharma, Shanghai, China) through the tail vein; after continuous injection of L-NAME for 4 days, the rats in the PE + oe-METTL3 + si-circSETD2 group were further injected with 30 μl lentiviral vector oe-circSETD2 and si-circSETD2 (GenePharma) at the virus titer of 5 × 107 PFU/mL. The rats were euthanized on the 16th day of pregnancy. Then, the chorionic trophoblast tissues were isolated from the placenta of pregnant rats and divided into 2 parts, with 1 part for extraction and detection of tissue RNA, and the other part fixed in the buffer containing 10% formalin, embedded in paraffin, and made into 5 μm sections.
Full List of Potential Compound(s) Related to This m6A-centered Crosstalk
JA24: Pre-eclampsia 1 Compound(s) Regulating the Disease Click to Show/Hide the Full List
 Compound Name Digibind Phase 2 [2]
Synonyms
Digoxin Immune Fab (ovine); Ovine antidigoxin polyclonal antibody fragments (pre-eclampsia), BTG; Ovine antidigoxin polyclonal antibody fragments (pre-eclampsia), GlaxoSmithKline/Glenveigh
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External Link
TTD: D0ME1L
References
Ref 1 N6-methyladenosine modification in trophoblasts promotes circSETD2 expression, inhibits miR-181a-5p, and elevates MCL1 transcription to reduce apoptosis of trophoblasts. Environ Toxicol. 2023 Feb;38(2):422-435. doi: 10.1002/tox.23683. Epub 2022 Oct 19.
Ref 2 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)