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ZNF503 accelerates aggressiveness of hepatocellular carcinoma cells by down-regulation of GATA3 expression and regulated by microRNA-495.

ABSTRACT: Zinc finger protein ZNF503 is an important regulator during developmental process and tumor initiation. ZNF503 drives tumor development and process and was cancer-specific dysregulated in cancers. However, its expression and function in hepatocellular carcinoma (HCC) still need to be studied and elucidated. In this study, we demonstrated for the first time that ZNF503 mRNA and protein was up-regulated in HCC tissues and cell lines. Clinical data showed that high ZNF503 was significantly correlated with poor prognostic features, including advanced TNM stage and venous invasion. Moreover, ZNF503 was identified as a potential 5-year prognostic marker of HCC patients. Notably, ZNF503 promoted migration, invasion and EMT progress. ZNF503 was recruited to GATA3 promoter and inhibited its expression. GATA3 inhibited HCC cells migration, invasion and EMT process. Furthermore, we demonstrated that ZNF503 expression was regulated by miR-495. In HCC tissues. MiR-495 has an inverse correlation with ZNF503 expression. Conclusively, our data revealed that ZNF503 promoted migration, invasion and EMT process through regulating GATA3 expression, which was regulated by miR-495, suggesting the potential therapeutic value for HCC.

SUBMITTER: Yin G

PROVIDER: S-EPMC6614650 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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ZNF503 accelerates aggressiveness of hepatocellular carcinoma cells by down-regulation of GATA3 expression and regulated by microRNA-495.

Yin Guozhi G Liu Zhikui Z Wang Yufeng Y Sun Liankang L Wang Liang L Yao Bowen B Liu Runkun R Chen Tianxiang T Niu Yongshen Y Liu Qingguang Q

American journal of translational research 20190615 6

Zinc finger protein ZNF503 is an important regulator during developmental process and tumor initiation. ZNF503 drives tumor development and process and was cancer-specific dysregulated in cancers. However, its expression and function in hepatocellular carcinoma (HCC) still need to be studied and elucidated. In this study, we demonstrated for the first time that ZNF503 mRNA and protein was up-regulated in HCC tissues and cell lines. Clinical data showed that high ZNF503 was significantly correlat ...[more]

PMID: 31312355

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Project description:BackgroundMicroRNAs (miRNAs) play crucial roles in regulating eukaryotic gene expression. Recent studies indicated that aberrantly expressed miRNAs are involved in the pathogenesis of ankylosing spondylitis (AS). Indeed, hsa-miR-495-3p (miR-495) has been reported as an anti-oncogene in different cancers. However, the role of miR-495 in AS is still unknown.MethodsIn this study, quantitative real-time polymerase chain reaction (PCR) was used to detect the expression of miR-495 in the peripheral blood mononuclear cells (PBMCs), whole blood, and serum of patients with AS. Bisulfite-specific PCR sequencing and methylated DNA immunoprecipitation were used to detect the methylation in the promoter region of miR-495. To determine the influence of miR-495 expression on the target gene, programmed cell death 10 (PDCD10), dual luciferase reporter assays together with an adenoviral vector containing the miR-495 locus were used. Receiver operating characteristic (ROC) curves were used to evaluate the efficacy of miR-495 as a diagnostic biomarker of AS. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes pathway analysis, and western blotting were used to explore the potential role of miR-495 in AS pathogenesis and the mechanism by which it facilitates AS pathogenesis.ResultsmiR-495 is down-regulated and the promoter region of miR-495 is highly methylated in AS. The expression of miR-495 is negatively associated with PDCD10 expression in both patients with AS and healthy controls. Further experiments showed that PDCD10 can be targeted by miR-495. The ROC curves of miR-495 suggested that it is a very specific and sensitive biomarker for AS diagnosis. Bioinformatics analysis and signal pathway studies indicated that miR-495 can down-regulate ?-catenin and transforming growth factor-?1.ConclusionsOur studies indicated that down-regulation of miR-495 can be used as a potential molecular marker for the diagnosis and treatment of AS, thus providing new insights into the role of miRNAs in AS pathology.

Dataset Information

ZNF503 accelerates aggressiveness of hepatocellular carcinoma cells by down-regulation of GATA3 expression and regulated by microRNA-495.

Publications

ZNF503 accelerates aggressiveness of hepatocellular carcinoma cells by down-regulation of GATA3 expression and regulated by microRNA-495.

Similar Datasets

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