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

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.

scholarly journals New Insights into the Role of miR-29a in Hepatocellular Carcinoma: Implications in Mechanisms and Theragnostics

2021 ◽  
Vol 11 (3) ◽  
pp. 219
Author(s):  
Ya-Ling Yang ◽  
Yen-Hsiang Chang ◽  
Chia-Jung Li ◽  
Ying-Hsien Huang ◽  
Ming-Chao Tsai ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tumor Microenvironment ◽  
Crucial Role ◽  
Human Cancer ◽  
Metabolic Adaptation ◽  
Advanced Hcc ◽  
Diagnosis And Prognosis ◽  
Competitive Endogenous Rnas ◽  
Growing Body

Hepatocellular carcinoma (HCC) remains one of the most lethal human cancer globally. For advanced HCC, curable plan for advanced HCC is yet to be established, and the prognosis remains poor. The detail mechanisms underlying the progression of HCC tumorigenicity and the corruption of tumor microenvironment (TME) is complex and inconclusive. A growing body of studies demonstrate microRNAs (miRs) are important regulators in the tumorigenicity and TME development. Notably, mounting evidences indicate miR-29a play a crucial role in exerting hepatoprotective effect on various types of stress and involved in the progression of HCC, which elucidates their potential theragnostic implications. In this review, we reviewed the advanced insights into the detail mechanisms by which miR-29a dictates carcinogenesis, epigenetic program, and metabolic adaptation, and implicated in the sponging activity of competitive endogenous RNAs (ceRNA) and the TME components in the scenario of HCC. Furthermore, we highlighted its clinical significance in diagnosis and prognosis, as well as the emerging therapeutics centered on the activation of miR-29a.

scholarly journals The emerging role of microRNAs and long noncoding RNAs in drug resistance of hepatocellular carcinoma

2019 ◽  
Vol 18 (1) ◽  
Author(s):  
Ling Wei ◽  
Xingwu Wang ◽  
Liyan Lv ◽  
Jibing Liu ◽  
Huaixin Xing ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Drug Resistance ◽  
Human Cancer ◽  
Noncoding Rnas ◽  
Circular Rna ◽  
Long Noncoding Rnas ◽  
Protein Coding ◽  
Multiple Tumor ◽  
Nucleolar Rnas

Abstract Hepatocellular carcinoma (HCC) is the fifth most common malignancy worldwide and the second most lethal human cancer. A portion of patients with advanced HCC can significantly benefit from treatments with sorafenib, adriamycin, 5-fluorouracil and platinum drugs. However, most HCC patients eventually develop drug resistance, resulting in a poor prognosis. The mechanisms involved in HCC drug resistance are complex and inconclusive. Human transcripts without protein-coding potential are known as noncoding RNAs (ncRNAs), including microRNAs (miRNAs), small nucleolar RNAs (snoRNAs), long noncoding RNAs (lncRNAs) and circular RNA (circRNA). Accumulated evidences demonstrate that several deregulated miRNAs and lncRNAs are important regulators in the development of HCC drug resistance which elucidates their potential clinical implications. In this review, we summarized the detailed mechanisms by which miRNAs and lncRNAs affect HCC drug resistance. Multiple tumor-specific miRNAs and lncRNAs may serve as novel therapeutic targets and prognostic biomarkers for HCC.

scholarly journals Role of the Mitochondrial Citrate-malate Shuttle in Hras12V-Induced Hepatocarcinogenesis: A Metabolomics-Based Analysis

Metabolites ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. 193
Author(s):  
Chuanyi Lei ◽  
Jun Chen ◽  
Huiling Li ◽  
Tingting Fan ◽  
Xu Zheng ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Bioinformatics Analysis ◽  
Lipid Biosynthesis ◽  
Pentose Phosphate ◽  
Glutathione Metabolism ◽  
Ras Signaling ◽  
Significant Finding ◽  
Ras Oncogene

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.

scholarly journals Distinct molecular etiologies of male and female hepatocellular carcinoma

BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Heini M. Natri ◽  
Melissa A. Wilson ◽  
Kenneth H. Buetow
Keyword(s):  
Gene Expression ◽  
Hepatocellular Carcinoma ◽  
Sex Differences ◽  
Differential Expression ◽  
Differential Expression Analysis ◽  
Regulation Of Transcription ◽  
Male And Female ◽  
Differential Effects ◽  
Pathway Enrichment

Abstract Background Sex-differences in cancer occurrence and mortality are evident across tumor types; men exhibit higher rates of incidence and often poorer responses to treatment. Targeted approaches to the treatment of tumors that account for these sex-differences require the characterization and understanding of the fundamental biological mechanisms that differentiate them. Hepatocellular Carcinoma (HCC) is the second leading cause of cancer death worldwide, with the incidence rapidly rising. HCC exhibits a male-bias in occurrence and mortality, but previous studies have failed to explore the sex-specific dysregulation of gene expression in HCC. Methods Here, we characterize the sex-shared and sex-specific regulatory changes in HCC tumors in the TCGA LIHC cohort using combined and sex-stratified differential expression and eQTL analyses. Results By using a sex-specific differential expression analysis of tumor and tumor-adjacent samples, we uncovered etiologically relevant genes and pathways differentiating male and female HCC. While both sexes exhibited activation of pathways related to apoptosis and cell cycle, males and females differed in the activation of several signaling pathways, with females showing PPAR pathway enrichment while males showed PI3K, PI3K/AKT, FGFR, EGFR, NGF, GF1R, Rap1, DAP12, and IL-2 signaling pathway enrichment. Using eQTL analyses, we discovered germline variants with differential effects on tumor gene expression between the sexes. 24.3% of the discovered eQTLs exhibit differential effects between the sexes, illustrating the substantial role of sex in modifying the effects of eQTLs in HCC. The genes that showed sex-specific dysregulation in tumors and those that harbored a sex-specific eQTL converge in clinically relevant pathways, suggesting that the molecular etiologies of male and female HCC are partially driven by differential genetic effects on gene expression. Conclusions Sex-stratified analyses detect sex-specific molecular etiologies of HCC. Overall, our results provide new insight into the role of inherited genetic regulation of transcription in modulating sex-differences in HCC etiology and provide a framework for future studies on sex-biased cancers.

scholarly journals Homeobox genes and Hepatocellular Carcinoma

2019 ◽  
Author(s):  
Kwei-Yan Liu ◽  
Li-Ting Wang ◽  
Shih-Hsien Hsu ◽  
Shen-Nien Wang
Keyword(s):  
Hepatocellular Carcinoma ◽  
Hox Genes ◽  
Viral Infections ◽  
Human Cancer ◽  
Control Cell ◽  
Environmental Toxins ◽  
Regulatory Mechanisms ◽  
Transcription Factor Family ◽  
Potential Use

Hepatocellular carcinoma (HCC) is the fifth most common type of cancer, and is the third leading cause of cancer-related deaths each year. It involves a multi-step progression and is strongly associated with chronic inflammation induced by the intake of environmental toxins and/or viral infections (i.e., hepatitis B and C viruses). Although several genetic dysregulations are considered to be involved in disease progression, the detailed regulatory mechanisms are not well defined. Homeobox (Hox) genes that encode transcription factors with homeodomains control cell growth, differentiation, and morphogenesis in embryonic development. Recently, more aberrant expressions of Hox genes were found in a wide variety of human cancer, including HCC. In this review, we summarize the currently available evidence related to the role of Hox genes in the development of HCC. The objective is to determine the roles of this conserved transcription factor family and its potential use as a therapeutic target in future investigations.

scholarly journals Distinct molecular etiologies of male and female hepatocellular carcinoma

2019 ◽  
Author(s):  
Heini M Natri ◽  
Melissa A Wilson ◽  
Kenneth H Buetow
Keyword(s):  
Gene Expression ◽  
Hepatocellular Carcinoma ◽  
Sex Differences ◽  
Differential Expression ◽  
Differential Expression Analysis ◽  
Regulation Of Transcription ◽  
Male And Female ◽  
Differential Effects ◽  
Pathway Enrichment

Abstract Background: Sex-differences in cancer occurrence and mortality are evident across tumor types; men exhibit higher rates of incidence and often poorer responses to treatment. Targeted approaches to the treatment of tumors that account for these sex-differences require the characterization and understanding of the fundamental biological mechanisms that differentiate them. Hepatocellular Carcinoma (HCC) is the second leading cause of cancer death worldwide, with the incidence rapidly rising. HCC exhibits a male-bias in occurrence and mortality, but previous studies have failed to explore the sex-specific dysregulation of gene expression in HCC. Methods: Here, we characterize the sex-shared and sex-specific regulatory changes in HCC tumors in the TCGA LIHC cohort using combined and sex-stratified differential expression and eQTL analyses. Results: By using a sex-specific differential expression analysis of tumor and tumor-adjacent samples, we uncovered etiologically relevant genes and pathways differentiating male and female HCC. While both sexes exhibited activation of pathways related to apoptosis and cell cycle, males and females differed in the activation of several signaling pathways, with females showing PPAR pathway enrichment while males showed PI3K, 305 PI3K/AKT, FGFR, EGFR, NGF, GF1R, Rap1, DAP12, and IL-2 signaling pathway enrichment. Using eQTL analyses, we discovered germline variants with differential effects on tumor gene expression between the sexes. 24.3% of the discovered eQTLs exhibit differential effects between the sexes, illustrating the substantial role of sex in modifying the effects of eQTLs in HCC. The genes that showed sex-specific dysregulation in tumors and those that harbored a sex-specific eQTL converge in clinically relevant pathways, suggesting that the molecular etiologies of male and female HCC are partially driven by differential genetic effects on gene expression. Conclusions: Sex-stratified analyses detect sex-specific molecular etiologies of HCC. Overall, our results provide new insight into the role of inherited genetic regulation of transcription in modulating sex-differences in HCC etiology and provide a framework for future studies on sex-biased cancers.

scholarly journals Distinct molecular etiologies of male and female hepatocellular carcinoma

2019 ◽  
Author(s):  
Heini M Natri ◽  
Melissa A Wilson ◽  
Kenneth H Buetow
Keyword(s):  
Gene Expression ◽  
Hepatocellular Carcinoma ◽  
Sex Differences ◽  
Differential Expression ◽  
Differential Expression Analysis ◽  
Regulation Of Transcription ◽  
Male And Female ◽  
Differential Effects ◽  
Pathway Enrichment

Abstract Background: Sex-differences in cancer occurrence and mortality are evident across tumor types; men exhibit higher rates of incidence and often poorer responses to treatment. Targeted approaches to the treatment of tumors that account for these sex-differences require the characterization and understanding of the fundamental biological mechanisms that differentiate them. Hepatocellular Carcinoma (HCC) is the second leading cause of cancer death worldwide, with the incidence rapidly rising. HCC exhibits a male-bias in occurrence and mortality, but previous studies have failed to explore the sex-specific dysregulation of gene expression in HCC. Methods: Here, we characterize the sex-shared and sex-specific regulatory changes in HCC tumors in the TCGA LIHC cohort using combined and sex-stratified differential expression and eQTL analyses. Results: By using a sex-specific differential expression analysis of tumor and tumor-adjacent samples, we uncovered etiologically relevant genes and pathways differentiating male and female HCC. While both sexes exhibited activation of pathways related to apoptosis and cell cycle, males and females differed in the activation of several signaling pathways, with females showing PPAR pathway enrichment while males showed PI3K, 305 PI3K/AKT, FGFR, EGFR, NGF, GF1R, Rap1, DAP12, and IL-2 signaling pathway enrichment. Using eQTL analyses, we discovered germline variants with differential effects on tumor gene expression between the sexes. 24.3% of the discovered eQTLs exhibit differential effects between the sexes, illustrating the substantial role of sex in modifying the effects of eQTLs in HCC. The genes that showed sex-specific dysregulation in tumors and those that harbored a sex-specific eQTL converge in clinically relevant pathways, suggesting that the molecular etiologies of male and female HCC are partially driven by differential genetic effects on gene expression. Conclusions: Sex-stratified analyses detect sex-specific molecular etiologies of HCC. Overall, our results provide new insight into the role of inherited genetic regulation of transcription in modulating sex-differences in HCC etiology and provide a framework for future studies on sex-biased cancers.

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

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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