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M6A demethylase FTO stabilizes LINK-A to exert oncogenic roles via MCM3-mediated cell cycle progression and HIF-1α activation

ABSTRACT: To further delineate the downstream regulatory mechanism underlying the oncogenic roles of LINK-A, we performed mass spectrometry (MS) analyses to identify proteins precipitated with LINK-A in KYSE450 and YES2 cells. In total, 43 and 14 LINK-A-interacting proteins were identified in KYSE450 and YES2 cells, respectively, and 7 of these interacting proteins were identified in both cell lines

ORGANISM(S): Homo Sapiens

SUBMITTER: Zhihua Liu

PROVIDER: PXD045414 | iProX | Fri Sep 15 00:00:00 BST 2023

REPOSITORIES: iProX

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m6A Demethylase FTO Stabilizes LINK-A to Exert Oncogenic Roles via MCM3-Mediated Cell Cycle Progression and HIF-1α Activation

Project description:We identified that the m6A demethylase FTO demethylates and stabilizes a lncRNA long intergenic noncoding RNA for kinase activation (LINK-A) during ESCC chemoresistance. LINK-A directly interacts with minichromosome maintenance complex component 3 (MCM3) and increases the phosphorylation of MCM3 at Ser112 by cyclin-dependent kinase 1 (CDK1), which facilitates MCM3 incorporation into the MCM2-7 complex and subsequent chromatin loading, promoting cell cycle progression. On the other hand, LINK-A insulates the interaction between MCM3 and HIF-1α to free HIF-1α. The enhancement of HIF-1α transcriptional activity reprograms metabolic status from OXPHOS to glycolysis. Additionally, targeting LINK-A substantially sensitized ESCC patient-derived xenografts (PDXs) to first-line chemotherapy, thus indicating LINK-A is a promising target for cancer treatment.

2023-10-15 | GSE224079 | GEO