Dataset Information

Circular RNA Expression Profiles and the Pro-tumorigenic Function of CircRNA_10156 in Hepatitis B Virus-Related Liver Cancer.

ABSTRACT: Liver cancer is one of the most common malignant tumors in the world. Circular RNAs (circRNAs) perform important functions in cancer progression and are regarded as prospective biomarkers for cancer diagnosis and therapy. Here, we used the high-throughput RNA sequencing technology in conjunction with bioinformatics tools to profile circRNA expression in patients with HBV-related liver cancer. A total of 13,124 circRNAs were identified in HBV-related liver cancer, approximately 86.25% of which were sense-overlapping circRNAs. Moreover, 2,996 circRNAs exhibited different expression patterns between liver cancer tissues and matched pericancerous tissues. Function annotation indicated that these aberrantly expressed circRNAs were primarily engaged in cellular processes and cancer-associated pathways. Notably, the circRNA-miRNA interaction networks showed that 6,020 circRNAs were predicted to target 1,654 miRNAs. Quantitative RT-PCR (qRT-PCR) assay indicated that ten randomly selected circRNAs displayed consistent expression patterns with the sequencing results. We further predicted that circRNA_10156 might work as a molecular sponge of miR-149-3p, which served an important function in tumor development. Consequently, our results demonstrated that depletion of circRNA_10156 upregulated miR-149-3p, reduced Akt1 expression, and suppressed liver cancer cell proliferation. The present study will facilitate the elucidation of biological functions of circRNAs in the progression of HBV-related liver cancer providing prospective biomarkers and therapeutic targets for this disease. Our findings also reveal that circRNA_10156 might represent a promising therapeutic target for liver cancer management.

SUBMITTER: Wang M

PROVIDER: S-EPMC7330659 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Circular RNA Expression Profiles and the Pro-tumorigenic Function of CircRNA_10156 in Hepatitis B Virus-Related Liver Cancer.

Wang Man M Gu Bianli B Yao Guoliang G Li Peifeng P Wang Kun K

International journal of medical sciences 20200530 10

Liver cancer is one of the most common malignant tumors in the world. Circular RNAs (circRNAs) perform important functions in cancer progression and are regarded as prospective biomarkers for cancer diagnosis and therapy. Here, we used the high-throughput RNA sequencing technology in conjunction with bioinformatics tools to profile circRNA expression in patients with HBV-related liver cancer. A total of 13,124 circRNAs were identified in HBV-related liver cancer, approximately 86.25% of which we ...[more]

PMID: 32624692

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Project description:BackgroundCircular RNAs (circRNAs) have been shown to play important regulatory roles in a range of both pathological and physiological contexts, but their functions in the context of skin aging remain to be clarified. In the present study, we therefore, profiled circRNA expression profiles in four pairs of aged and non-aged skin samples to identify identifying differentially expressed circRNAs that may offer clinical value as biomarkers of the skin aging process.MethodsWe utilized an RNA-seq to profile the levels of circRNAs in eyelid tissue samples, with qRT-PCR being used to confirm these RNA-seq results, and with bioinformatics approaches being used to predict downstream target miRNAs for differentially expressed circRNAs.ResultsIn total, we identified 571 circRNAs with 348 and 223 circRNAs being up and downregulated that were differentially expressed in aged skin samples compared to young skin samples. The top 10 upregulated circRNAs in aged skin sample were hsa_circ_0123543, hsa_circ_0057742, hsa_circ_0088179, hsa_circ_0132428, hsa_circ_0094423, hsa_circ_0008166, hsa_circ_0138184, hsa_circ_0135743, hsa_circ_0114119, and hsa_circ_0131421. The top 10 reduced circRNAs were hsa_circ_0101479, hsa_circ_0003650, hsa_circ_0004249, hsa_circ_0030345, hsa_circ_0047367, hsa_circ_0055629, hsa_circ_0062955, hsa_circ_0005305, hsa_circ_0001627, and hsa_circ_0008531. Functional enrichment analyses revealed the potential functionality of these differentially expressed circRNAs. The top 3 enriched gene ontology (GO) terms of the host genes of differentially expressed circRNAs are regulation of GTPase activity, positive regulation of GTPase activity and autophagy. The top 3 enriched KEGG pathway ID are Lysine degradation, Fatty acid degradation and Inositol phosphate metabolism. The top 3 enriched reactome pathway ID are RAB GEFs exchange GTP for GDP on RABs, Regulation of TP53 Degradation and Regulation of TP53 Expression and Degradation. Six circRNAs were selected for qRT-PCR verification, of which 5 verification results were consistent with the sequencing results. Moreover, targeted miRNAs, such as hsa-miR-588, hsa-miR-612, hsa-miR-4487, hsa-miR-149-5p, hsa-miR-494-5p were predicted for circRna-miRna interaction networks.ConclusionOverall, these results offer new insights into circRNA expression profiles, potentially highlighting future avenues for research regarding the roles of these circRNAs in the context of skin aging.

Project description:OBJECTIVE: The number of patients with HCV-related cirrhosis is increasing, leading to a rising risk of complications and death. Prognostic stratification in patients with early-stage cirrhosis is still challenging. We aimed to develop and validate a clinically useful prognostic index based on genomic and clinical variables to identify patients at high risk of disease progression. DESIGN: We developed a prognostic index, comprised of a 186-gene signature validated in our previous genome-wide profiling study, bilirubin (>1 mg/dL) and platelet count (<100 000/mm3), in an Italian HCV cirrhosis cohort (training cohort, n=216, median follow-up 10 years). The gene signature test was implemented using a digital transcript counting (nCounter) assay specifically developed for clinical use and the prognostic index was evaluated using archived specimens from an independent cohort of HCV-related cirrhosis in the USA (validation cohort, n=145, median follow-up 8 years). RESULTS: In the training cohort, the prognostic index was associated with hepatic decompensation (HR=2.71, p=0.003), overall death (HR=6.00, p<0.001), hepatocellular carcinoma (HR=3.31, p=0.001) and progression of Child-Turcotte-Pugh class (HR=6.70, p<0.001). The patients in the validation cohort were stratified into high-risk (16%), intermediate-risk (42%) or low-risk (42%) groups by the prognostic index. The high-risk group had a significantly increased risk of hepatic decompensation (HR=7.36, p<0.001), overall death (HR=3.57, p=0.002), liver-related death (HR=6.49, p<0.001) and all liver-related adverse events (HR=4.98, p<0.001). CONCLUSIONS: A genomic and clinical prognostic index readily available for clinical use was successfully validated, warranting further clinical evaluation for prognostic prediction and clinical trial stratification and enrichment for preventive interventions. 90 liver tissue needle biopsy specimens from patients with histologically proven cirrhosis lacking evidence and a history of hepatic decompensation or HCC.

Project description:OBJECTIVE: The number of patients with HCV-related cirrhosis is increasing, leading to a rising risk of complications and death. Prognostic stratification in patients with early-stage cirrhosis is still challenging. We aimed to develop and validate a clinically useful prognostic index based on genomic and clinical variables to identify patients at high risk of disease progression. DESIGN: We developed a prognostic index, comprised of a 186-gene signature validated in our previous genome-wide profiling study, bilirubin (>1?mg/dL) and platelet count (<100?000/mm3), in an Italian HCV cirrhosis cohort (training cohort, n=216, median follow-up 10?years). The gene signature test was implemented using a digital transcript counting (nCounter) assay specifically developed for clinical use and the prognostic index was evaluated using archived specimens from an independent cohort of HCV-related cirrhosis in the USA (validation cohort, n=145, median follow-up 8?years). RESULTS: In the training cohort, the prognostic index was associated with hepatic decompensation (HR=2.71, p=0.003), overall death (HR=6.00, p<0.001), hepatocellular carcinoma (HR=3.31, p=0.001) and progression of Child-Turcotte-Pugh class (HR=6.70, p<0.001). The patients in the validation cohort were stratified into high-risk (16%), intermediate-risk (42%) or low-risk (42%) groups by the prognostic index. The high-risk group had a significantly increased risk of hepatic decompensation (HR=7.36, p<0.001), overall death (HR=3.57, p=0.002), liver-related death (HR=6.49, p<0.001) and all liver-related adverse events (HR=4.98, p<0.001). CONCLUSIONS: A genomic and clinical prognostic index readily available for clinical use was successfully validated, warranting further clinical evaluation for prognostic prediction and clinical trial stratification and enrichment for preventive interventions. 145 liver tissue needle biopsy specimens from U.S. HCV cirrhosis cohort patients with histologically proven cirrhosis lacking evidence and a history of hepatic decompensation or HCC.

Dataset Information

Circular RNA Expression Profiles and the Pro-tumorigenic Function of CircRNA_10156 in Hepatitis B Virus-Related Liver Cancer.

Publications

Circular RNA Expression Profiles and the Pro-tumorigenic Function of CircRNA_10156 in Hepatitis B Virus-Related Liver Cancer.

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