A Nucleolar Stress-Specific p53-miR-101 Molecular Circuit Functions as an Intrinsic Tumor-Suppressor Network.

ABSTRACT:

Background

Activation of intrinsic p53 tumor-suppressor (TS) pathways is an important principle underlying cancer chemotherapy. It is necessary to elucidate the precise regulatory mechanisms of these networks to create new treatment strategies.

Methods

Comprehensive analyses were carried out by microarray. Expression of miR-101 was analyzed by clinical samples of lung adenocarcinomas.

Findings

We discovered a functional link between p53 and miR-101, which form a molecular circuit in response to nucleolar stress. Inhibition of RNA polymerase I (Pol I) transcription resulted in the post-transcriptional activation of miR-101 in a p53-dependent manner. miR-101 induced G2 phase-specific feedback regulation of p53 through direct repression of its target, EG5, resulting in e

SUBMITTER: Fujiwara Y 

PROVIDER: S-EPMC6085539 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature