Adenylate Kinase 4 Modulates the Resistance of Breast Cancer Cells to Tamoxifen through an m⁶A-Based Epitranscriptomic Mechanism.

ABSTRACT: N⁶-methyladenosine (m⁶A) is the most abundant internal modification in mRNA and this methylation constitutes an important regulatory mechanism for the stability and translational efficiency of mRNA. In this study, we found that the protein levels of adenylate kinase 4 (AK4) and m⁶A writer METTL3 are significantly higher in tamoxifen-resistant (TamR) MCF-7 cells than in parental cells. The TamR MCF-7 cells also exhibit increased methylation at multiple m⁶A consensus motif sites in the 5' untranslated region (5' UTR) of AK4 mRNA, and genetic depletion of METTL3 in TamR MCF-7 cells led to a diminished AK4 protein level and attenuated resistance to tamoxifen. In addition, we observed augmented levels of reactive oxygen species (ROS) and p38 activity

SUBMITTER: Liu X 

PROVIDER: S-EPMC7704734 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature