Translation of the circular RNA circ?-catenin promotes liver cancer cell growth through activation of the Wnt pathway.

ABSTRACT: BACKGROUND:Circular RNAs are a class of regulatory RNA transcripts, which are ubiquitously expressed in eukaryotes. In the current study, we evaluate the function of a novel circRNA derived from the ?-catenin gene locus, circ?-catenin. RESULTS:Circ?-catenin is predominantly localized in the cytoplasm and displays resistance to RNase-R treatment. We find that circ?-catenin is highly expressed in liver cancer tissues when compared to adjacent normal tissues. Silencing of circ?-catenin significantly suppresses malignant phenotypes in vitro and in vivo, and knockdown of this circRNA reduces the protein level of ?-catenin without affecting its mRNA level. We show that circ?-catenin affects a wide spectrum of Wnt pathway-related genes, and furthermore, circ?-catenin produces a novel 370-amino acid ?-catenin isoform that uses the start codon as the linear ?-catenin mRNA transcript and translation is terminated at a new stop codon created by circularization. We find that this novel isoform can stabilize full-length ?-catenin by antagonizing GSK3?-induced ?-catenin phosphorylation and degradation, leading to activation of the Wnt pathway. CONCLUSIONS:Our findings illustrate a non-canonical function of circRNA in modulating liver cancer cell growth through the Wnt pathway, which can provide novel mechanistic insights into the underlying mechanisms of hepatocellular carcinoma.

SUBMITTER: Liang WC 

PROVIDER: S-EPMC6486691 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature