m6A-centered Crosstalk Information

Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT05660
 [1]
m6A modification RN7SK RN7SK Mettl3 Methylation : m6A sites Direct Enhancement Non-coding RNA RN7SK CUL1  lncRNA       miRNA   circRNA
m6A Modification:
m6A Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
m6A Target RNA component of 7SK nuclear ribonucleoprotein (RN7SK)
 Targert Gene 
Epigenetic Regulation that have Cross-talk with This m6A Modification:
Epigenetic Regulation Type Non-coding RNA (ncRNA)
Epigenetic Regulator RNA component of 7SK nuclear ribonucleoprotein (RN7SK) snRNA View Details
Regulated Target Cullin 1 (CUL1) View Details
Crosstalk Relationship m6A  →  ncRNA Enhancement
Crosstalk Mechanism m6A regulators directly modulate the functionality of ncRNAs through specific targeting ncRNA
Crosstalk Summary RNA component of 7SK nuclear ribonucleoprotein (RN7SK) was identified as a small nuclear RNA that interacts with m6A readers. m6A readers recognized and facilitated secondary structure formation of m6A-modified RN7SK, which in turn prevented m6A reader mRNA degradation from exonucleases. Thus, a positive feedback circuit between RN7SK and m6A readers is established in tumor cells. From findings on the interaction with RN7SK, m6A readers, such as EWS RNA binding protein 1 (EWSR1), KH RNA binding domain containing, signal transduction-associated 1 (KHDRBS1) and IGF2BP3, were identified and shown to boost Wnt/beta-catenin signaling and tumorigenesis by suppressing translation of Cullin1 (Cullin 1 (CUL1)) which is regulated by METTL3 and YTHDC2.
Responsed Drug mitoxantrone (MIT)
 Drug Info 
Pathway Response Wnt signaling pathway hsa04310
Cell Process mRNA decay
In-vitro Model
 BEAS-2B Normal Homo sapiens CVCL_0168
NCI-H1299 Lung large cell carcinoma Homo sapiens CVCL_0060
NCI-H1975 Lung adenocarcinoma Homo sapiens CVCL_1511
A-549 Lung adenocarcinoma Homo sapiens CVCL_0023
PC-9 Lung adenocarcinoma Homo sapiens CVCL_B260
BEL-7404 Endocervical adenocarcinoma Homo sapiens CVCL_6568
BEL-7402 Endocervical adenocarcinoma Homo sapiens CVCL_5492
Hep-G2 Hepatoblastoma Homo sapiens CVCL_0027
SW1990 Pancreatic adenocarcinoma Homo sapiens CVCL_1723
PANC-1 Pancreatic ductal adenocarcinoma Homo sapiens CVCL_0480
MKN45 Gastric adenocarcinoma Homo sapiens CVCL_0434
MGC-803 Gastric mucinous adenocarcinoma Homo sapiens CVCL_5334
HCT 116 Colon carcinoma Homo sapiens CVCL_0291
HT29 Colon cancer Mus musculus CVCL_A8EZ
In-vivo Model For the generation of PDX mouse models, fresh LUSC specimens (2-3 mm3), which were from Shanghai Chest Hospital, were implanted into 4- to 6-week-old athymic nude mice (Jiesijie, Shanghai, China). After successful tumor growth was confirmed, the tumor tissues were passaged and implanted into the next generation of mice. The third to fifth generations of PDX-bearing mice were used for drug administration. When tumors reached approximately 200 mm3, mice were injected daily with DMSO (no. ST038, Beyotime Biotechnology, Shanghai, China) with or without MIT (no. S2485, 5 mg/kg, Selleck, Houston, TX) or HYD (no. S1896, 20 mg/kg, Selleck) (n = 5 mice/group). Tumor growth was monitored, and sizes were calculated by 0.5 × L × W2 (L indicating length and W indicating width). The mice were euthanized at day 28 after implantation. All animal experiments were approved by the institutional ethics committee of Shanghai Chest Hospital (approval number KS(Y)21381).
References
Ref 1 A positive feedback circuit between RN7SK snRNA and m(6)A readers is essential for tumorigenesis. Mol Ther. 2023 Jun 7;31(6):1615-1635. doi: 10.1016/j.ymthe.2022.12.013. Epub 2022 Dec 24.