IndraLab

"Similarly, in HBE cells transformed with 2% cigarette smoke extract (CSE), increased levels of m 6 A and upregulated expression of METTL3 were observed after 48 hours of treatment. xref In particular, METTL3-mediated increases of m 6 A on the 3’ UTR of the tumor suppressor Zbtb4 resulted in decreased ZBTB4 expression through YTHDF2-mediated mRNA decay. xref As a result, decreased ZBTB4 expression promoted cigarette smoke (CS)-induced EMT and carcinogenesis. xref In another study, human bronchial epithelial (BEAS-2B) cells exposed to CS had downregulated expression of YTHDC2. xref Mechanistically, YTHDC2 was found to bind m 6 A sites on the transcript of the tumor suppressor Cyld and promoted Cyld mRNA stability. xref As CYLD normally inhibits the NF- κ B pathway, decreased YTHDC2 expression after CS exposure can promote cancer cell proliferation by modulating the CYLD/NF- κ B axis in CS-induced lung cancer. xref "

"CYLD inhibits the NF-κB pathway by deubiquitinating key factors, including NF-κB essential modulators IKKg and TRAF2 ( xref )."

"Previous studies report that CYLD negatively regulates NF-κB signaling by removing K63- and M1-linked polyubiquitin chains from key signaling molecules, including NF-κB essential modulator, tumor necrosis factor (TNF)-associated factor (TRAF) 2, TRAF6, and Receptor-interacting serine/threonine-protein kinase 1, in familial cylindromatosis tumors. xref – xref Additionally, Tauriello et al xref demonstrated that CYLD inhibits the Wnt pathway by deubiquitinating disheveled in familial cylindromatosis tumors."