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

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 cytoplas...

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Vydané v:	Genome Biology Ročník 20; číslo 1; s. 84
Hlavní autori:	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
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	London BioMed Central 26.04.2019 Springer Nature B.V BMC
Predmet:	Amino acids Animal Genetics and Genomics Animals beta catenin beta Catenin - genetics Bioinformatics Biomedical and Life Sciences Carcinogenesis Carcinoma, Hepatocellular - etiology Cell activation Cell growth Cell Line, Tumor Cell Movement Circular RNA Coding capacity Cytoplasm eukaryotic cells Evolutionary Biology Gene expression Gene Knockdown Techniques Glycogen Synthase Kinase 3 beta - metabolism Hepatocellular carcinoma Hepatocytes hepatoma Human Genetics Humans Kinases Life Sciences Ligands Liver cancer Liver Neoplasms - etiology loci messenger RNA Mice, Nude Microbial Genetics and Genomics MicroRNAs Mortality neoplasm cells Neoplasm Metastasis Non-coding RNA Online data bases phenotype Phenotypes Phosphorylation Plant Genetics and Genomics protein content Proteins Ribonuclease RNA - metabolism RNA, Circular start codon Stop codon tissues Transcription Translation translation (genetics) Tumorigenesis Wnt pathway Wnt protein Wnt Signaling Pathway β-Catenin Circular RNA Cell growth Wnt pathway Non-coding RNA Coding capacity
ISSN:	1474-760X, 1474-7596, 1474-760X
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Shrnutí:	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.
Bibliografia:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23
ISSN:	1474-760X 1474-7596 1474-760X
DOI:	10.1186/s13059-019-1685-4