Bioinformatic Analysis to Identify a Multi-mRNA Signature for the Prediction of Metastasis in Hepatocellular Carcinoma

2020 ◽  
Vol 39 (11) ◽  
pp. 2028-2039
Author(s):  
Longgen Liu ◽  
Bingrui Wang ◽  
Qiucheng Han ◽  
Chao Zhen ◽  
Jichang Li ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Bioinformatic Analysis ◽  
Prediction Of Metastasis

Bioinformatic analysis of the prognostic value of the lncRNAs encoding snoRNAs in hepatocellular carcinoma

BioFactors ◽  
2018 ◽  
Vol 45 (2) ◽  
pp. 244-252 ◽  
Author(s):  
Qingyao Zhu ◽  
Hongjie Yang ◽  
Peng Cheng ◽  
Qian Han
Keyword(s):  
Hepatocellular Carcinoma ◽  
Prognostic Value ◽  
Bioinformatic Analysis

scholarly journals Bioinformatic Analysis of Circular RNA-Associated ceRNA Network Associated with Hepatocellular Carcinoma

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Jiacheng Wu ◽  
Shui Liu ◽  
Yien Xiang ◽  
Xianzhi Qu ◽  
Yingjun Xie ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Pathway Analysis ◽  
Target Genes ◽  
Kegg Pathway ◽  
Interaction Network ◽  
Bioinformatic Analysis ◽  
Differentially Expressed ◽  
Qrt Pcr ◽  
Cerna Network ◽  
Kegg Pathway Analysis

Hepatocellular carcinoma (HCC) is the sixth most common cancer worldwide and is associated with a high mortality rate and poor treatment efficacy. In an attempt to investigate the mechanisms involved in the pathogenesis of HCC, bioinformatic analysis and validation by qRT-PCR were performed. Three circRNA GEO datasets and one miRNA GEO dataset were selected for this purpose. Upon combined biological prediction, a total of 11 differentially expressed circRNAs, 15 differentially expressed miRNAs, and 560 target genes were screened to construct a circRNA-related ceRNA network. GO analysis and KEGG pathway analysis were performed for the 560 target genes. To further screen key genes, a protein-protein interaction network of the target genes was constructed using STRING, and the genes and modules with higher degree were identified by MCODE and CytoHubba plugins of Cytoscape. Subsequently, a module was screened out and subjected to GO enrichment analysis and KEGG pathway analysis. This module included eight genes, which were further screened using TCGA. Finally, UBE2L3 was selected as a key gene and the hsa_circ_0009910–miR-1261–UBE2L3 regulatory axis was established. The relative expression of the regulatory axis members was confirmed by qRT-PCR in 30 pairs of samples, including HCC tissues and adjacent nontumor tissues. The results suggested that hsa_circ_0009910, which was upregulated in HCC tissues, participates in the pathogenesis of HCC by acting as a sponge of miR-1261 to regulate the expression of UBE2L3. Overall, this study provides support for the possible mechanisms of progression in HCC.

scholarly journals High Squalene Epoxidase in Tumors Predicts Worse Survival in Patients With Hepatocellular Carcinoma: Integrated Bioinformatic Analysis on NAFLD and HCC

2020 ◽  
Vol 27 (1) ◽  
pp. 107327482091466
Author(s):  
Tingting Shen ◽  
Yunfei Lu ◽  
Qin Zhang
Keyword(s):  
Hepatocellular Carcinoma ◽  
Messenger Rna ◽  
Disease Free Survival ◽  
Bioinformatic Analysis ◽  
Gene Expression Omnibus ◽  
The Cancer Genome Atlas ◽  
Squalene Epoxidase ◽  
Nonalcoholic Fatty Liver ◽  
Kaplan Meier ◽  
High Level

This study aimed to identify candidate biomarkers for predicting outcomes in nonalcoholic fatty liver disease (NAFLD) and hepatocellular carcinoma (HCC). Using Gene Expression Omnibus and The Cancer Genome Atlas (TCGA) databases, we identified common upregulated differential expressed genes (DEGs) in patients with NAFLD/nonalcoholic steatohepatitis (NASH) and HCC and conducted survival analysis of these upregulated DEGs with HCC outcomes. Two common upregulated DEGs including squalene epoxidase (SQLE) and EPPK1 messenger RNA (mRNA) were significantly upregulated in NAFLD, NASH, and HCC tissues, both in GSE45436 ( P < .001) and TCGA profile ( P < .001). Both SQLE and EPPK1 mRNA were upregulated in 15.56% and 8.06% patients with HCC in TCGA profile. Overexpression of SQLE in tumors was significantly associated with worse overall survival (OS) and disease-free survival (DFS) in patients with HCC (log-rank P = .027 and log-rank P = .048, respectively), while no statistical significances of OS and DFS were found in EPPK1 groups (both log-rank P > .05). For validation, SQLE upregulation contributed to significantly worse OS in patients wih HCC using Kaplan-Meier plotter analysis (hazard ratio = 1.43, 95% confidence interval: 1.01-2.02, log-rank P = .043). In addition, high level of SQLE significantly associated with advanced neoplasm histologic grade, advanced AJCC stage, and α-fetoprotein elevation ( P = .036, .045, and .029, respectively). Squalene epoxidase is associated with OS and DFS and serves as a novel prognostic biomarker for patients with HCC.

A Tumor Progression Model for Hepatocellular Carcinoma: Bioinformatic Analysis of Genomic Data

2006 ◽  
Vol 131 (4) ◽  
pp. 1262-1270 ◽  
Author(s):  
Terence C.W. Poon ◽  
Nathalie Wong ◽  
Paul B.S. Lai ◽  
Magnus Rattray ◽  
Philip J. Johnson ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tumor Progression ◽  
Genomic Data ◽  
Bioinformatic Analysis ◽  
Progression Model ◽  
Tumor Progression Model

scholarly journals Roles of the miR-139-5p/CCT5 axis in hepatocellular carcinoma: a bioinformatic analysis

2021 ◽  
Vol 18 (15) ◽  
pp. 3556-3564
Author(s):  
Jingjing Xu ◽  
Yuan Zhang ◽  
Cheng Liu ◽  
Ping Yan ◽  
Zongguo Yang
Keyword(s):  
Hepatocellular Carcinoma ◽  
Bioinformatic Analysis

scholarly journals CircMTO1 suppresses hepatocellular carcinoma progression via the miR-541-5p/ZIC1 axis by regulating Wnt/β-catenin signaling pathway and epithelial-to-mesenchymal transition

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Dandan Li ◽  
Jiawei Zhang ◽  
Jing Yang ◽  
Jie Wang ◽  
Runling Zhang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tumor Growth ◽  
Epithelial To Mesenchymal Transition ◽  
Bioinformatic Analysis ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Signal Pathways ◽  
Mesenchymal Transition

AbstractCircRNA mitochondrial tRNA translation optimization 1 (circMTO1) functions as a tumor suppressor usually and is related to the progression of many tumors, including hepatocellular carcinoma (HCC). CircMTO1 is downregulated in HCC as compared to adjacent nontumor tissue, which may suppress the HCC progression by certain signal pathways. However, the underlying signal pathway remains largely unknown. The interactions between circMTO1 and miR-541-5p were predicted through bioinformatics analysis and verified using pull-down and dual-luciferase reporter assays. CCK-8, transwell, and apoptosis assays were performed to determine the effect of miR-541-5p on HCC progression. Using bioinformatic analysis, dual-luciferase reporter assay, RT-qPCR, and western blot, ZIC1 was found to be the downstream target gene of miR-541-5p. The regulatory mechanisms of circMTO1, miR-541-5p, and ZIC1 were investigated using in vitro and in vivo rescue experiments. The results depicted that silencing circMTO1 or upregulating miR-541-5p expression facilitated HCC cell proliferation, migration, and invasion and inhibited apoptosis. CircMTO1 silencing upregulated the expression of downstream ZIC1 regulators of the Wnt/β-catenin pathway markers, β-catenin, cyclin D1, c-myc, and the mesenchymal markers N-cadherin, Vimentin, and MMP2, while the epithelial marker E-cadherin was downregulated. MiR-541-5p knockdown had the opposite effect and reversed the effect of circMTO1 silencing on the regulation of downstream ZIC1 regulators. Intratumoral injection of miR-541-5p inhibitor suppressed tumor growth and reversed the effect of circMTO1 silencing on the promotion of tumor growth in HCC. These findings indicated that circMTO1 suppressed HCC progression via the circMTO1/ miR-541-5p/ZIC1 axis by regulating Wnt/β-catenin signaling and epithelial-to-mesenchymal transition, making it a novel therapeutic target.

scholarly journals TMEM147 promotes  hepatocellular carcinoma progress  by inducing EGFR/MAPK activity

2020 ◽  
Author(s):  
Chengyi Sun ◽  
Jing Xu ◽  
She Tian ◽  
Yanqing Liu ◽  
Changhao Zhu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Plasma Membrane ◽  
Mapk Pathway ◽  
Aerobic Glycolysis ◽  
Bioinformatic Analysis ◽  
Mapk Signaling ◽  
Clinicopathological Characteristics ◽  
Loss Of Function ◽  
Abnormal Glucose Metabolism

Abstract Backgroud: Hepatocellular carcinoma (HCC) is characterized by rapid early proliferation and distant metastasis and is extremely difficult to treat. Aerobic glycolysis is a hallmark of abnormal glucose metabolism in cancer cells as has been shown to be associated with tumor proliferation and metastasis; however, the mechanisms underlying aerobic glycolysis remain unclear. Methods: Immunohistochemistry (IHC) and qRT-PCR was performed to investigate the association between TMEM147 expression and the clinicopathological characteristics and prognosis of patients with HCC. Loss- and gain-of function assays were performed to investigate the role of TMEM147 in proliferation, metastasis and glycolysis in vitro and vivo. Bioinformatic analysis and rescue assay were used to demonstrated the TMEM147 interacted with EGFR and promoted its retromer-mediated recycling back to the plasma membrane.Results: we identified TMEM147 as a protein that was highly expressed and associated with poor survival in patients with HCC. Both gain- and loss-of-function studies revealed that TMEM147 acted as a key oncoprotein by promoting HCC growth, metastasis, and glycolysis via the EGFR/ MAPK signaling pathway. Mechanistically, TMEM147 interacted with EGFR and promoted its retromer-mediated recycling back to the plasma membrane, thus increasing the stability of EGFR and prolonging activation of the downstream MAPK pathway.Conclusion: Collectively, these results demonstrated the role and functional mechanism of TMEM147 in HCC, and indicated that TMEM147 may represent a prognostic biomarker and potential therapeutic target for HCC.

scholarly journals LncRNA MYLK-AS1 facilitates tumor progression and angiogenesis by targeting miR-424-5p/E2F7 axis and activating VEGFR-2 signaling pathway in hepatocellular carcinoma

2020 ◽  
Vol 39 (1) ◽  
Author(s):  
Fei Teng ◽  
Ju-Xiang Zhang ◽  
Qi-Meng Chang ◽  
Xu-Bo Wu ◽  
Wei-Guo Tang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tumor Progression ◽  
Signaling Pathway ◽  
Cell Lines ◽  
Rna Binding ◽  
Normal Liver ◽  
Bioinformatic Analysis ◽  
Luciferase Reporter ◽  
E2f Transcription Factor

Abstract Background Long non-coding RNAs (lncRNAs) are crucial in the invasion, angiogenesis, progression, and metastasis of hepatocellular carcinoma (HCC). The lncRNA MYLK-AS1 promotes the growth and invasion of HCC through the EGFR/HER2-ERK1/2 signaling pathway. However, the clinical significance of MYLK-AS1 in HCC still needs to be further determined. Methods Bioinformatic analysis was performed to determine the potential relationship among MYLK-AS1, miRNAs and mRNAs. A total of 156 samples of normal liver and paired HCC tissues from HCC patients were used to evaluate MYLK-AS1 expression by qRT-PCR. Human HCC cell lines were used to evaluate the colony formation, cell proliferation, migration, invasion, cell cycle and apoptosis after transfection of lentiviral short-hairpin RNAs (shRNAs) targeting MYLK-AS1 or MYLK-AS1 vectors. The competitive endogenous RNA (ceRNA) mechanism was clarified using fluorescence in situ hybridization (FISH), Western blotting, qPCR, RNA binding protein immunoprecipitation (RIP), and dual luciferase reporter analysis. Results MYLK-AS1 up-regulation was detected in the HCC tumor tissues and cell lines associated with the enhancement of the angiogenesis and tumor progression. The down-regulation of MYLK-AS1 reversed the effects on angiogenesis, proliferation, invasion and metastasis in the HCC cells and in vivo. MYLK-AS1 acted as ceRNA, capable of regulating the angiogenesis in HCC, while the microRNA miR-424-5p was the direct target of MYLK-AS1. Promoting the angiogenesis and the tumor proliferation, the complex MYLK-AS1/miR-424-5p activated the VEGFR-2 signaling through E2F7, whereas the specific targeting of E2F transcription factor 7 (E2F7) by miR-424-5p, was indicated by the mechanism studies. Conclusions MYLK-AS1 and E2F7 are closely related to some malignant clinicopathological features and prognosis of HCC, thus the MYLK-AS1/ miR-424-5p/E2F7 signaling pathway might represent a promising treatment strategy to combat HCC.

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