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Translation of the circular RNA circβ-catenin promotes liver cancer cell growth through activation of the Wnt pathway
- Liang, Wei-Cheng, Wong, Cheuk-Wa, Liang, Pu-Ping, Shi, Mai, Cao, Ye, Rao, Shi-Tao, Tsui, Stephen Kwok-Wing, Waye, Mary Miu-Yee, Zhang, Qi, Fu, Wei-Ming, Zhang, Jin-Fang
- Genome biology 2019 v.20 no.1 pp. 84
- amino acids, beta catenin, cell growth, circular RNA, cytoplasm, eukaryotic cells, gene expression, hepatoma, loci, messenger RNA, neoplasm cells, phenotype, phosphorylation, protein content, start codon, stop codon, tissues, translation (genetics)
- 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 β-catenin gene locus, circβ-catenin. RESULTS: Circβ-catenin is predominantly localized in the cytoplasm and displays resistance to RNase-R treatment. We find that circβ-catenin is highly expressed in liver cancer tissues when compared to adjacent normal tissues. Silencing of circβ-catenin significantly suppresses malignant phenotypes in vitro and in vivo, and knockdown of this circRNA reduces the protein level of β-catenin without affecting its mRNA level. We show that circβ-catenin affects a wide spectrum of Wnt pathway-related genes, and furthermore, circβ-catenin produces a novel 370-amino acid β-catenin isoform that uses the start codon as the linear β-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 β-catenin by antagonizing GSK3β-induced β-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.