Journal
ONCOGENE
Volume 35, Issue 5, Pages 651-661Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/onc.2015.124
Keywords
-
Funding
- National Natural Science foundation [81300411, 81372662]
- Fundamental Research Funds for the Central Universities [2015QN144]
Ask authors/readers for more resources
Metastasis is one of the main causes of death in patients with colorectal cancer (CRC). Brg-1 is a central component of the SWItch/Sucrose NonFermentable chromatin-remodeling complex, which features a bromodomain and helicase/ATPase activity. The gene encoding Brg-1 is frequently mutated or silenced in human cancers. Several reports have proposed Brg-1 as a tumor suppressor; however, little is known about its role in oncogenesis and metastasis. Here we demonstrated that decreased Brg-1 regulates a novel miR-550a-5p/RNF43/Wnt/beta-catenin signaling pathway, to promote CRC metastasis in vitro and in vivo. In particular, we used high-throughput RNA-sequencing analysis to show that Brg-1 negatively regulates miR-550a-5p in CRC cells. We further found that Brg-1 inhibits the transcriptional activity of miR-550a-5p promoter, and that decreased Brg-1 expression increased miR-550a-5p expression. We also identified ring finger 43 (RNF43), an inhibitor of Wnt/beta-catenin signaling, as a target of miR-550a-5p. Knockdown of Brg-1 by small interfering RNA led to decreased RNF43 expression, increased Wnt signaling and increased CRC cell migration and invasion. This novel pathway defines a new function for Brg-1 and provides potential targets for the treatment of Brg-1 mutant and loss-of-function tumors.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available