Integrated bioinformatics analysis reveals role of the LINC01093/miR‑96‑5p/ZFAND5/NF‑κB signaling axis in hepatocellular carcinoma

The activation of the Ras signaling pathway is a crucial process in hepatocarcinogenesis. Till now, no reports have scrutinized the role of dynamic metabolic changes in Ras oncogene-induced transition of the normal and precancerous liver cells to hepatocellular carcinoma in vivo. In the current study, we attempted a comprehensive investigation of Hras12V transgenic mice (Ras-Tg) by concatenating nontargeted metabolomics, transcriptomics analysis, and targeted-metabolomics incorporating [U-13C] glucose. A total of 631 peaks were detected, out of which 555 metabolites were screened. Besides, a total of 122 differently expressed metabolites (DEMs) were identified, and they were categorized and subtyped with the help of variation tendency analysis of the normal (W), precancerous (P), and hepatocellular carcinoma (T) liver tissues. Thus, the positive or negative association between metabolites and the hepatocellular carcinoma and Ras oncogene were identified. The bioinformatics analysis elucidated the hepatocarcinogenesis-associated significant metabolic pathways: glycolysis, mitochondrial citrate-malate shuttle, lipid biosynthesis, pentose phosphate pathway (PPP), cholesterol and bile acid biosynthesis, and glutathione metabolism. The key metabolites and enzymes identified in this analysis were further validated. Moreover, we confirmed the PPP, glycolysis, and conversion of pyruvate to cytosol acetyl-CoA by mitochondrial citrate-malate shuttle, in vivo, by incorporating [U-13C] glucose. In summary, the current study presented the comprehensive bioinformatics analysis, depicting the Ras oncogene-induced dynamic metabolite variations in hepatocarcinogenesis. A significant finding of our study was that the mitochondrial citrate-malate shuttle plays a crucial role in detoxification of lactic acid, maintenance of mitochondrial integrity, and enhancement of lipid biosynthesis, which, in turn, promotes hepatocarcinogenesis.

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Bioinformatics Analysis and Insights for The Role of COMMD7 in Hepatocellular Carcinoma

10.21203/rs.3.rs-79438/v1 ◽

2020 ◽

Author(s):

Xuehui Peng ◽

Yonggang He ◽

Xiaobing Huang ◽

Nan You ◽

Huiying Gu ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Bioinformatics Analysis ◽

Tissue Expression ◽

The Cancer Genome Atlas ◽

Research Progress ◽

Kaplan Meier ◽

Tumor Tissues ◽

Cancer Genome Atlas ◽

Kaplan Meier Plotter

Abstract Background: The tumorigenesis and development of hepatocellular carcinoma (HCC) is a process involving multiple factors. The COMMDs family proteins were reported to play important roles in various disease and cancers including HCC. We previously found COMMD7 acted as a HCC-promotion factor; however, further understanding on COMMD7 was needed. We conducted these bioinformatics analysis for the purpose of comprehensive understanding of the functional role of COMMD7 in HCC.Methods: The bioinformatics analysis of COMMD7 were launched by online platforms including KEGG, GEPIA, cBioportal, Gene Ontology and The Kaplan-Meier plotter. Data from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) were downloaded, and the data analysis and processing were conducted by RStudio (version 1.3.959) software.Results: The expression profile results of COMMD7 in TCGA and GTEx database suggested that COMMD7 expressed highly in liver tumor tissues and positively related with poorer prognosis (p<0.01); COMMD7 also contributed to the early development of HCC as its higher expression resulted in progression from stage I to stage III (p<0.01). Based on our previous studies, COMMD7 may target NF-κB signaling and CXCL10 to enhance the proliferation of hepatoma cells so that promoting the development of HCC. Conclusions：This study updates the current studies about the newly recognized roles of COMMD7 in the progression of HCC, summarizing the research progress and prospects of COMMD7 comprehensively, offering an outlook for the future investigation and targeted therapy of HCC.

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Large-scale sequencing combined with bioinformatics analysis reveals KLF8 an apoptosis repressor in hepatocellular carcinoma

10.21203/rs.2.13333/v1 ◽

2019 ◽

Author(s):

Hao Xing ◽

Jin Zhang ◽

Kai-Lian Zheng ◽

Ming-Da Wang ◽

Jun Han ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Large Scale ◽

Target Genes ◽

Bioinformatics Analysis ◽

Primary Liver Cancer ◽

Panoramic View ◽

Chip Sequencing ◽

Apoptotic Effect ◽

First Time

Abstract Backgrounds Hepatocellular carcinoma (HCC) is the most frequent primary liver cancer and the third leading cause of cancer death. Krüppel-like factor 8 (KLF8) is an oncogene and has been shown playing an important role in HCC, but the major involved signaling pathways are still unknown. Here, we systematically analyzed the role of KLF8 in HCC using RNA sequencing and the anti-H3K27 acetylation ChIP sequencing combined with bioinformatics analysis, and the results of data mining. Results The results in this study showed that KLF8 worked as a transcription repressor in HCC and the main directly regulated ones were apoptosis-related genes. Furthermore, we verified the combination of KLF8 with some predicted target genes by ChIP, which supported the effectiveness of our analysis. Besides, we demonstrated that HMGA2 and MMP7, two predicted targets, were important participants in KLF8 mediated anti-apoptotic effect in HCC. Conclusions Our work offers a panoramic view of KLF8’s role in HCC for the first time and facilitates the discovery of new targets for HCC via KLF8.

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Clinical value and potential mechanisms of LINC00221 in hepatocellular carcinoma based on integrated analysis

Epigenomics ◽

10.2217/epi-2020-0363 ◽

2021 ◽

Author(s):

Yanlin Feng ◽

Souraka Tapara Dramani Maman ◽

Xinyu Zhu ◽

Xuefang Liu ◽

Christian Cedric Bongolo ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Operating Characteristic ◽

Bioinformatics Analysis ◽

Validation Cohort ◽

Characteristic Curve ◽

Integrated Analysis ◽

Clinical Value ◽

Serum Samples ◽

Functional Roles

This study aimed to unveil the functional roles of LINC00221 in hepatocellular carcinoma (HCC). A discovery cohort and a validation cohort were respectively used to identify and verify the clinical value of LINC00221 in HCC. Bioinformatics analysis was performed to explore its potential mechanisms. LINC00221 was upregulated in HCC tissues and serum samples. Survival analysis and receiver operating characteristic curve further revealed its prognostic and diagnostic roles. Exploration of the mechanism showed that LINC00221 might exert a pro-cancer role via the lncRNA–miRNA–mRNA network. Our study reveals that upregulated LINC00221 can serve as a potential diagnostic and prognostic biomarker and provides novel clues as to the role of LINC00221 in HCC.

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Upregulated expression of MTFR2 as a novel biomarker predicts poor prognosis in hepatocellular carcinoma by bioinformatics analysis

Future Oncology ◽

10.2217/fon-2020-1160 ◽

2021 ◽

Author(s):

Dan Li ◽

YanMei Ji ◽

JiaLong Guo ◽

Qiang Guo

Keyword(s):

Hepatocellular Carcinoma ◽

Poor Prognosis ◽

Bioinformatics Analysis ◽

Independent Predictor ◽

Cancer Stage ◽

Clinical Role ◽

P53 Signaling ◽

Dismal Prognosis ◽

P53 Signaling Pathway

Aim: The authors investigated the clinical role of MTFR2 in hepatocellular carcinoma (HCC) progression. Results: MTFR2 expression and methylation were abnormal in HCC tissues, and HCC patients with increased MTFR2 expression or methylation had poor or better overall survival, respectively. In addition, increased MTFR2 expression was correlated with age, grade, cancer stage and T stage. MTFR2 was an independent predictor of dismal prognosis in HCC patients. MTFR2 was involved in HCC progression by modulating the cell cycle, homologous recombination, DNA replication, p53 signaling pathway, etc. The ten hub genes were overexpressed in HCC tissues and were linked to cancer stage and dismal prognosis in HCC patients. Conclusion: MTFR2 could be a prospective biomarker of poor prognosis in individuals with HCC.

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Systematic expression and bioinformatics analysis of fibrinogen-like protein 1 in human cancer and its co-expression network

10.21203/rs.3.rs-147981/v1 ◽

2021 ◽

Author(s):

Qian Wang ◽

Shu-zhen Chen ◽

Hua-wei Zhang

Keyword(s):

Hepatocellular Carcinoma ◽

Immune Response ◽

Bioinformatics Analysis ◽

Human Cancer ◽

Transcriptional Level ◽

Human Cell Lines ◽

Human Carcinoma ◽

Pathway Enrichment ◽

Coexpression Networks

Abstract Background Fibrinogen-like protein 1 was initially found in a study on hepatocellular carcinoma and it is overexpressed in human cell lines and rats. Recently, investigations have focused on fibrinogen-like protein 1 dysfunction in carcinogenesis. Our study aims to determine the role of fibrinogen-like protein 1 and its possible role in human carcinoma. Methods Fibrinogen-like protein 1 expression in different neoplasms was assessed by Oncomine. Fibrinogen-like protein 1 coexpression networks in various cancers were established using Coexpedia. Finally, we investigated the potential functions of fibrinogen-like protein 1 with gene ontology and pathway enrichment analyses with the FunRich V3. Results Fibrinogen-like protein 1 was overexpressed in several kinds of neoplasms at the transcriptional level. Coexpression networks showed that fibrinogen-like protein 1 regulates immune response and lipid related pathways. Conclusions The present results offer the possibility that fibrinogen-like protein 1 acts as a therapeutic target for some types of cancers and may take part in carcinogenesis.

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Bioinformatics Analysis and Insights for the Role of COMMD7 in Hepatocellular Carcinoma

10.21203/rs.3.rs-113846/v1 ◽

2020 ◽

Author(s):

Jing Li ◽

Xuehui Peng ◽

Yonggang He ◽

Xiaobing Huang ◽

Nan You ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Bioinformatics Analysis ◽

Tissue Expression ◽

The Cancer Genome Atlas ◽

Research Progress ◽

Kaplan Meier ◽

Tumor Tissues ◽

Cancer Genome Atlas ◽

Kaplan Meier Plotter

Abstract Background: The tumorigenesis and development of hepatocellular carcinoma (HCC) is a process involving multiple factors. The COMMDs family proteins were reported to play important roles in various disease and cancers including HCC. We previously found COMMD7 acted as a HCC-promotion factor; however, further understanding on COMMD7 was needed. We conducted these bioinformatics analysis for the purpose of comprehensive understanding of the functional role of COMMD7 in HCC.Methods: The bioinformatics analysis of COMMD7 were launched by online platforms including KEGG, GEPIA, cBioportal, Gene Ontology and The Kaplan-Meier plotter. Data from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) were downloaded, and the data analysis and processing were conducted by RStudio (version 1.3.959) software.Results: The expression profile results of COMMD7 in TCGA and GTEx database suggested that COMMD7 expressed highly in liver tumor tissues and positively related with poorer prognosis (p<0.01); COMMD7 also contributed to the early development of HCC as its higher expression resulted in progression from stage I to stage III (p<0.01). Based on our previous studies, COMMD7 may target NF-κB signaling and CXCL10 to enhance the proliferation of hepatoma cells so that promoting the development of HCC. Conclusions：This study updates the current studies about the newly recognized roles of COMMD7 in the progression of HCC, summarizing the research progress and prospects of COMMD7 comprehensively, offering an outlook for the future investigation and targeted therapy of HCC.

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Integrative analysis of the characteristic of lipid metabolism-related genes for the prognostic prediction of hepatocellular carcinoma

10.21203/rs.3.rs-27431/v1 ◽

2020 ◽

Author(s):

Wenbiao Chen ◽

Jun Zeng ◽

Minglin Ou ◽

Donge Tang

Keyword(s):

Hepatocellular Carcinoma ◽

Lipid Metabolism ◽

Bioinformatics Analysis ◽

Biological Function ◽

Molecular Characteristics ◽

Data Set ◽

External Data ◽

Validation Set ◽

Prognostic Prediction

Abstract Background Dysregulation of lipid metabolism has been implicated in the progression of hepatocellular carcinoma (HCC). We therefore investigated the molecular characteristics of lipid-metabolism-related genes for the prognostic prediction of HCC. Methods Multi-dimensional bioinformatics analysis was conducted to comprehensively analyzed the lipid metabolism-related genes (IMRG) and construct the prognostic prediction signature. Results A total of 770 HCC patients and their corresponding 776 IMRGs were downloaded from three databases. The HCC patients were classified into 2 molecular clusters, which were associated with overall survival, clinical characteristics, and immune cells. The biological function of the differentially expressed IMRGs in the 2 clusters showed that the genes were associated with tumor-related metabolism pathways. A 6 IMRGs signature (6-IS), including FMO3, SLC11A1, RNF10, KCNH2, ME1, and ZIC2 were established for HCC prognostic prediction, which was found to be an independent prognostic factor. Performance of the 6-IS prognostic signature was verified in a validation set and compared with an external data set. Results revealed that the 6-IS signature could effectively predict the prognosis of patients with HCC. Conclusion This study provides new insights into the role of IMRG in the pathogenesis of HCC and presents a novel signature 6-IS to predict the prognosis of HCC.

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Clinicopathological role of miR-30a-5p in hepatocellular carcinoma tissues and prediction of its function with bioinformatics analysis

OncoTargets and Therapy ◽

10.2147/ott.s111431 ◽

2016 ◽

Vol Volume 9 ◽

pp. 5061-5071 ◽

Cited By ~ 8

Author(s):

Gang Chen ◽

Wenting Huang ◽

Zu-xuan Chen ◽

Rongquan He ◽

Yuzhuang Wu ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Bioinformatics Analysis

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Bcl-2 Associated Athanogene 2 (BAG2) is Associated With Progression and Prognosis of Hepatocellular Carcinoma: A Bioinformatics-Based Analysis

Pathology & Oncology Research ◽

10.3389/pore.2021.594649 ◽

2021 ◽

Vol 27 ◽

Author(s):

Xi Zhang ◽

Junjun Zhang ◽

Yang Liu ◽

Jie Li ◽

Juan Tan ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Ribosome Biogenesis ◽

Bioinformatics Analysis ◽

Progression Free Survival ◽

Cell Counting ◽

Free Survival ◽

Prognostic Analysis ◽

Worse Prognosis ◽

Disease Specific

Background: Bcl-2 associated athanogene2 (BAG2) is reported to act as an oncogene or a tumor-suppressor in tumors in a context-dependent way; however, its function in hepatocellular carcinoma (HCC) remains unclear.Methods: Immunohistochemistry (IHC) staining, cell counting kit-8 (CCK-8) assay, apoptotic assay, cell invasion assay and a set of bioinformatics tools were integrated to analyze the role of BAG2 in hepatocellular carcinoma.Results: BAG2 was significantly up-regulated in HCC. Prognostic analysis indicated that HCC patients with high expression of BAG2 had significantly shorter overall survival, progression free survival and disease specific survival. Besides, silencing BAG2 in HCC cells impaired cell proliferation, facilitated apoptosis and repressed invasion of the cells. Bioinformatics analysis showed that BAG2 might regulate ribosome biogenesis in HCC.Conclusion: This study revealed that the up-regulated BAG2 in HCC was associated with a worse prognosis and might favor the progression of the disease.

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