Timeless-Stimulated miR-5188-FOXO1/β-Catenin-c-Jun Feedback Loop Promotes Stemness via Ubiquitination of β-Catenin in Breast Cancer.

ABSTRACT: MicroRNAs (miRNAs) play an essential role in the self-renewal of breast cancer stem cells (BCCs). Our study aimed to clarify the role of proto-oncogene c-Jun-regulated miR-5188 in breast cancer progression and its association with Timeless-mediated cancer stemness. In the present study, we showed that miR-5188 exerted an oncogenic effect by inducing breast cancer stemness, proliferation, metastasis, and chemoresistance in vitro and in vivo. The mechanistic analysis demonstrated that miR-5188 directly targeted FOXO1, which interacted with β-catenin in the cytoplasm, facilitated β-catenin degradation, and impaired the nuclear accumulation of β-catenin, thus stimulating the activation of known Wnt targets, epithelial-mesenchymal transition (EMT) markers, and key regulators of cancer stemness.

SUBMITTER: Zou Y 

PROVIDER: S-EPMC6951841 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature