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Hsa_circ_0003945 promotes progression of hepatocellular carcinoma by mediating miR-34c-5p/LGR4/β-catenin axis activity.


ABSTRACT: Accumulating evidence suggests that circular RNAs (circRNAs) play essential roles in regulating cancer progression, but many circRNAs in hepatocellular carcinoma (HCC) remain unknown. Dysregulated circRNAs in HCC were identified through bioinformatics analysis of Gene Expression Omnibus data sets. Quantitative real-time PCR (qRT-PCR), Sanger sequencing, RNase R digestion and actinomycin D treatment were conducted to confirm the characterization of circRNAs. CCK-8, wound-healing and Transwell assays were performed to assess the functional roles of Hsa_circ_0003945 (Circ_0003945) in HCC cell lines. Subcellular fractionation and fluorescence in situ hybridization (FISH) were performed to locate Circ_0003945 in HCC cells. Dual-luciferase reporter assay was executed to verify the binding of Circ_0003945 to microRNAs (miRNAs) or the miRNAs to their target genes. In this study, we found that Circ_0003945 was upregulated in HCC tissue, and higher Circ_0003945 expression was positively correlated with tumour size and tumour stage. Furthermore, high plasma levels of circulating Circ_0003945 were confirmed in HCC patients compared with those in non-HCC groups. The functional experiments revealed that overexpression or knockdown of Circ_0003945 promoted or attenuated tumour growth and migration, respectively. Mechanistically, Circ_0003945 might exert as a miR-34c-5p sponge to upregulate the expression of leucine-rich repeat-containing G protein-coupled receptor 4 (LGR4), activating the β-catenin pathway, and finally facilitating HCC progression. Additionally, a β-catenin activator could reverse the effect of Circ_0003945 knockdown. In conclusion, Circ_0003945 exerts a tumour-promoting role in HCC cells by regulating the miR-34c-5p/LGR4/β-catenin axis, which may be a potential target for HCC therapy.

SUBMITTER: Lyu LH 

PROVIDER: S-EPMC8995453 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

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Hsa_circ_0003945 promotes progression of hepatocellular carcinoma by mediating miR-34c-5p/LGR4/β-catenin axis activity.

Lyu Li-Hua LH   Zhang Chun-Yan CY   Yang Wen-Jing WJ   Jin An-Li AL   Zhu Jie J   Wang Hao H   Liu Te T   Wang Bei-Li BL   Cheng Jian-Wen JW   Yang Xin-Rong XR   Guo Wei W  

Journal of cellular and molecular medicine 20220216 8


Accumulating evidence suggests that circular RNAs (circRNAs) play essential roles in regulating cancer progression, but many circRNAs in hepatocellular carcinoma (HCC) remain unknown. Dysregulated circRNAs in HCC were identified through bioinformatics analysis of Gene Expression Omnibus data sets. Quantitative real-time PCR (qRT-PCR), Sanger sequencing, RNase R digestion and actinomycin D treatment were conducted to confirm the characterization of circRNAs. CCK-8, wound-healing and Transwell ass  ...[more]

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