Oncogenic K-Ras suppresses global miRNA function.

ABSTRACT: K-Ras frequently acquires gain-of-function mutations (K-Ras^G12D being the most common) that trigger significant transcriptomic and proteomic changes to drive tumorigenesis. Nevertheless, oncogenic K-Ras-induced dysregulation of post-transcriptional regulators such as microRNAs (miRNAs) during oncogenesis is poorly understood. Here, we report that K-Ras^G12D promotes global suppression of miRNA activity, resulting in the upregulation of hundreds of targets. We constructed a comprehensive profile of physiological miRNA targets in mouse colonic epithelium and tumors expressing K-Ras^G12D using Halo-enhanced Argonaute pull-down. Combining this with parallel datasets of chromatin accessibility, transcriptome, and proteome, we uncovered that K-Ras^G12D su

SUBMITTER: Shui B 

PROVIDER: S-EPMC10527862 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature