scholarly journals Prognostic biomarker SMARCC1 and its association with immune infiltrates in hepatocellular carcinoma

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Xiaopeng Cai ◽  
Jiaming Zhou ◽  
Jingwen Deng ◽  
Zhi Chen
Keyword(s):  
Hepatocellular Carcinoma ◽  
Transcription Factors ◽  
Tissue Microarray ◽  
Prognostic Value ◽  
Expression Profiles ◽  
Biological Significance ◽  
Migration And Invasion ◽  
Mrna Levels ◽  
Immune Infiltration

Abstract Background Epigenetic alterations contribute greatly to metastasis and dissemination in hepatocellular carcinoma (HCC). SMARCC1, as a SWI/SNF chromatin remodeling factor, has been reported to play important roles in many cancers. For the first time, with the bioinformatics analysis and wet-bench experiments, we explored the biological significance of SMARCC1 and its potential as putative therapeutic target in HCC. Methods The mRNA expression profiles and prognostic value of SMARCC1 were analyzed in the Oncomine, UALCAN and Kaplan–Meier Plotter databases. The expression of SMARCC1 and associated clinicopathological factors were further evaluated using a tissue microarray. Differentially expressed genes associated with SMARCC1 in HCC were obtained and analyzed via the LinkedOmics and GEPIA databases and Cytoscape software. To verify the important role of SMARCC1 in HCC, we knocked down and overexpressed SMARCC1 in different hepatic cell lines and conducted several functional experiments. Then, we evaluated the mutation profiles and transcriptional regulators of SMARCC1 using the cBioPortal, COSMIC, CistromeDB and TCGA databases. Finally, we addressed the relationship of SMARCC1 expression with immune cell infiltration via TIMER database analysis. Results Through data mining and tissue microarray verification, we found that the protein and mRNA levels of SMARCC1 are high in tumor tissues, which has remarkable diagnostic value in HCC patients. SMARCC1 and its hub genes showed prognostic value in HCC. Furthermore, we confirmed that SMARCC1 influenced the proliferation, migration, and invasion of HCC cells. Moreover, correlation analyses revealed that SMARCC1 expression was positively correlated with ZBTB40 transcription factors and negatively correlated with the DNA methylation level. Overall, we found that SMARCC1 affects immune infiltration and plays a tumor-promoting role in HCC. Conclusions SMARCC1 is overexpressed and is a putative prognostic predictor in HCC. Due to the tumor-promoting role of SMARCC1, treatments inhibiting DNA methyltransferases and transcription factors or weakening the role of SMARCC1 in immune infiltration might improve the survival of HCC patients.

scholarly journals NTF3 Correlates With Prognosis and Immune Infiltration in Hepatocellular Carcinoma

2021 ◽  
Vol 8 ◽  
Author(s):  
Rongqiang Liu ◽  
Rongqi Li ◽  
Haoyuan Yu ◽  
Jianrong Liu ◽  
Shiyang Zheng ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Transcription Factors ◽  
Prognostic Factor ◽  
Liver Cancer ◽  
Potential Role ◽  
Immune Checkpoints ◽  
Cd4 Cells ◽  
Clinical Value ◽  
Immune Infiltration

Background: The potential role of Neurotrophic factor-3(NTF3) in liver cancer is unknown. Therefore, we aimed to explore the clinical value of NTF3 in hepatocellular carcinoma (HCC).Methods: We used a variety of databases to analyze the expression, relationship with prognosis and immune significance of NTF3 in liver cancer through bioinformatics.Results: NTF3 was low expressed in HCC and was an independent prognostic factor in patients with HCC. CIBERSORT analysis indicated that NTF3 expression was positively correlated with CD4+ cells, mast cells, NK cells, macrophages and B cells in the tumor microenvironment. Furthermore, we found that NTF3 expression was negatively correlated with the immune checkpoints PD-L1, TIGIT and TIM-3. Functional network analysis revealed that NTF3 regulates HCC progression through a variety of cancer-related kinases, transcription factors and signaling pathways.Conclusions: We demonstrate that NTF3 correlates with prognosis and immune infiltration in HCC.

scholarly journals Identification and integrative analysis of ACLY and related gene panels associated with immune microenvironment reveal prognostic significance in hepatocellular carcinoma

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yunfeng Xu ◽  
Ze Zhang ◽  
Da Xu ◽  
Xin Yang ◽  
Lina Zhou ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Prognostic Value ◽  
Cox Regression ◽  
Prognostic Significance ◽  
Gene Panel ◽  
Metabolic Reprogramming ◽  
Immune Checkpoints ◽  
Immune Microenvironment ◽  
Immune Infiltration

Abstract Background Cumulating evidence reveals the key role of aberrant lipogenesis and immunogenomic features in hepatocellular carcinoma (HCC). However, there are still obstacles in our understanding of the complicated interaction between metabolic reprogramming and tumor immune microenvironment. Methods We compared metabolomic, transcriptomic and immunogenomic characteristics of portal vein tumor thrombosis (PVTT) and primary tumor to seek valuable markers. Human HCC samples with PVTT (n  =  28) was analyzed through ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS). Transcript levels of mRNA in two cohorts from published database GEO (n  =  60) and TCGA (n  =  411) were downloaded to explore differentially expressed genes and functional enriched gene set. Evaluation of immune infiltration was estimated and validated from transcriptomic data in both cohorts through six immune deconvolution algorithms and in a high-resolution mode (CIBERSORTx). Survival analysis (Kaplan–Meier and multivariable Cox regression model) was performed to examine prognostic value of ACLY, related immune checkpoints and immune infiltration levels from TCGA cohort. LASSO regression was further conducted to determine a gene panel to further predict survival outcomes associated with ACLY. Results We identified a novel signature, ATP citrate lyase, through transcriptomic and metabolomic approaches. We demonstrated that the metabolism adaptations in both fatty acid and cholesterol biosynthesis triggered by ACLY oncogenic activation. We illustrated the crucial function of ACLY in lipogenesis and its potential interaction with immune microenvironment. CD276, a promising target in immune checkpoint blockade, showed correlation to ACLY and differential expression in ACLY risk classification. Combination of ACLY, CD276 and immune infiltration level and a novel ACLY-associated panel from a predictive model retrieved from published database validated the prognostic value to risk stratification in patients with HCC.ACLY blockade to counteract metabolic activation and immunosuppressive status of the tumor microenvironment highlighted attractive prospect for translational application. Conclusions We investigated ACLY and its indispensable role in metabolism, immune function and a prognostic gene panel in HCC. We anticipate that the multifaced role of ACLY may reveal the potential value for mechanistic research and combinational therapy, suggesting that the combination blockade of ACLY and immune checkpoints may work as a promising strategy.

scholarly journals Identification and integrative analysis of ACLY and related gene panels associated with immune microenvironment reveal prognostic significance in hepatocellular carcinoma

2021 ◽  
Author(s):  
Yunfeng Xu ◽  
Ze Zhang ◽  
Da Xu ◽  
Li-Na Zhou ◽  
Ying Zhu
Keyword(s):  
Hepatocellular Carcinoma ◽  
Prognostic Value ◽  
Cox Regression ◽  
Prognostic Significance ◽  
Gene Panel ◽  
Metabolic Reprogramming ◽  
Immune Checkpoints ◽  
Immune Microenvironment ◽  
Immune Infiltration

Abstract BackgroundCumulating evidence reveals the key role of aberrant lipogenesis and immunogenomic features in hepatocellular carcinoma (HCC). However, there are still obstacles in our understanding of the complicated interaction between metabolic reprogramming and tumor immune microenvironment.MethodsWe compared metabolomic, transcriptomic and immunogenomic characteristics of portal vein tumor thrombosis (PVTT) and primary tumor to seek valuable markers. Human HCC samples with PVTT (n = 28) was analyzed through ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS). Transcript levels of mRNA in two cohorts from published database GEO (n = 60) and TCGA (n = 411) were downloaded to explore differentially expressed genes and functional enriched gene set. Evaluation of immune infiltration was estimated and validated from transcriptomic data in both cohorts through six immune deconvolution algorithms (TIMER, CIBERSORT, quanTIseq, xCell, MCP-counter, EPIC) and in a high-resolution mode (CIBERSORTx). Survival analysis (Kaplan-Meier and multivariable Cox regression model) was performed to examine prognostic value of ACLY, related immune checkpoints and immune infiltration levels from TCGA cohort. LASSO regression was further conducted to determine a gene panel to further predict survival outcomes associated with ACLY.ResultsWe identified a novel signature, ATP citrate lyase, through transcriptomic and metabolomic approaches. We demonstrated that the metabolism adaptations in both fatty acid and cholesterol biosynthesis triggered by ACLY oncogenic activation. We illustrated the crucial function of ACLY in lipogenesis and its potential interaction with immune microenvironment. CD276, a promising target in immune checkpoint blockade, showed correlation to ACLY and differential expression in ACLY risk classification. Combination of ACLY, CD276 and immune infiltration level and a novel ACLY-associated panel from a predictive model retrieved from published database validated the prognostic value to risk stratification in patients with HCC. According to the survival outcome and correlation analysis, ACLY blockade to counteract metabolic activation and immunosuppressive status of the tumor microenvironment highlighted attractive prospect for translational application.ConclusionsWe investigated ACLY and its indispensable role in metabolism, immune function and a prognostic gene panel in HCC. We anticipate that the multifaced role of ACLY may reveal the potential value for mechanistic research and combinational therapy, suggesting that the combination blockade of ACLY and immune checkpoints may work as a promising strategy.

scholarly journals System Analysis of ROS-Related Genes in the Prognosis, Immune Infiltration, and Drug Sensitivity in Hepatocellular Carcinoma

2021 ◽  
Vol 2021 ◽  
pp. 1-30
Author(s):  
Jun Hui Xu ◽  
Yong Jun Guan ◽  
Zhen Dong Qiu ◽  
Xin Zhang ◽  
Liu Liu Zi ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Prognostic Model ◽  
Drug Sensitivity ◽  
System Analysis ◽  
Cox Regression ◽  
Migration And Invasion ◽  
Immune Infiltration ◽  
Prognosis Model

Hepatocellular carcinoma (HCC) is an aggressive malignant tumor with a poor prognosis. Reactive oxygen species (ROS) play an important role in tumors; however, the role of ROS-related genes is still unclear in HCC. Therefore, we analyzed the role of ROS-related genes in HCC via bioinformatics methods. Firstly, a prognosis model was constructed using LASSO Cox regression and multivariate analyses. We also investigated the potential function of the ROS-related genes and the correlation with immune infiltration, tumor stemness, and drug sensitivity. ICGC database was used for validation. Secondly, we further analyzed the role of 11 ROS-related genes in HCC. As a member of ROS gene family, the role of STK25 has remained unclear in HCC. We explored the biological function of STK25 using in vitro experiments. The present study was the first to construct a ROS-related prognostic model in HCC. The correlation of ROS-related genes with immune infiltration, tumor stemness, and drug sensitivity was dissected. Furthermore, we demonstrated that STK25 knockdown could increase the proliferation, migration, and invasion capacity of HCC cells.

scholarly journals A Pyroptosis-Related LncRNA Signature for Predicting Prognosis and Treatment in Hepatocellular Carcinoma

2021 ◽  
Author(s):  
Yuhao Zhang ◽  
Jiaxin Zhang ◽  
Fengxian Wei ◽  
Haodong Zhang ◽  
Dongdong Wang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Prognostic Value ◽  
Immune Cell ◽  
Cox Regression ◽  
Expression Profiles ◽  
Enrichment Analysis ◽  
Clinical Treatment ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Immune Infiltration

Abstract Background: Hepatocellular carcinoma (HCC), which carries a very bad prognosis, is a common malignant tumor worldwide. This study aim to identify a pyroptosis-related long non-coding RNA(pyLncRNA) prognostic signature in HCC by integrated bioinformatics analysis. Methods: All expression profiles of HCC were obtained from The Cancer Genome Atlas (TCGA) and pyroptosis-related genes were from the GSEA website. After identified differentially expressed pyLncRNAs, univariate Cox regression and Lasso analysis were used to identify a pyroptosis-related LncRNAs prognositic signature(py-LPS). Internal validation was used to validate the prognostic value of the py-LPS via the Kaplan-Meier(K-M) curve and receiver operating characteristic(ROC) curve. Additional, we established the nomogram and analyzed the correlation between the signature and immune immune infiltration as well as clinical treatment. Result: 7 pyLncRNAs were established the signature for HCC prognosis. K-M curves exhibited the low risk group presented a markedly longer OS than the high. Clinical subgroups analysis based age, gender, grade and stage yielded the similar results. The signature had an independent prognostic value for HCC(p<0.001). Nomogram estimated one-, three- and five-year survival were 0.777, 0.741 and 0.709. Then, gene set enrichment analysis(GSEA) demostrated significant pathways. Futhermore, we found immune cell infiltration and immunotherapy targets was associated with the signature,which could provided clinical recommendations for chemotherapy.Conclusion: In this study, a novel pyroptosis-related LncRNAs porgnostic signature of HCC, correlated with immune infiltration, could predict the survival of HCC patients and give suggestions for clinical treatment.

scholarly journals Circular RNA hsa_circ_101555 promotes hepatocellular carcinoma cell proliferation and migration by sponging miR-145-5p and regulating CDCA3 expression

2021 ◽  
Vol 12 (4) ◽  
Author(s):  
Xiaoguang Gu ◽  
Jianan Zhang ◽  
Yajuan Ran ◽  
Hena Pan ◽  
JinHong Jia ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Biological Effects ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Casein Kinase 1 ◽  
Mouse Xenograft Model ◽  
Hcc Cells

AbstractCircular RNAs have been reported to play significant roles in regulating pathophysiological processes while also guiding clinical diagnosis and treatment of hepatocellular carcinoma (HCC). However, only a few circRNAs have been identified thus far. Herein, we investigated the role of a specific closed-loop structure of hsa_circ_101555 that was generated by back-splicing of the host gene casein kinase 1 gamma 1 (CSNK1G1) in the development and proliferation of HCC. We investigated the expression of Hsa_circ_101555 in HCC and normal tissues using bioinformatics. The expression level of hsa_circ_101555 was further detected by fluorescence in situ hybridization and qRT-PCR in ten HCC patients. Transwell, migration, WST-1 assays, and colony formation assays were used to evaluate the role of hsa_circ_101555 in HCC development and proliferation. The regulatory mechanisms of hsa_circ_101555 in miR-145-5p and CDCA3 were determined by dual luciferase reporter assay. A mouse xenograft model was also used to determine the effect of hsa_circ_101555 on HCC growth in vivo. hsa_circ_101555 showed greater stability than the linear RNA; while in vitro and in vivo results demonstrated that hsa_circ_101555 silencing significantly suppressed cell proliferation, migration, and invasion of HCC cells. Rescue experiments further demonstrated that suppression of miR-145-5p significantly attenuated the biological effects of hsa_circ_101555 knockdown in HCC cells. We also identified a putative oncogene CDCA3 as a potential miR-145-5p target. Thus, our results demonstrated that hsa_circ_101555 might function as a competing endogenous RNA of miR-145-5p to upregulate CDCA3 expression in HCC. These findings suggest that hsa_circ_101555 may be a potential therapeutic target for patients with HCC.

PGC-1α is associated with C2C12 Myoblast differentiation

2014 ◽  
Vol 9 (11) ◽  
pp. 1030-1036 ◽  
Author(s):  
Yaqiu Lin ◽  
Yanying Zhao ◽  
Ruiwen Li ◽  
Jiaqi Gong ◽  
Yucai Zheng ◽  
...  
Keyword(s):  
Mrna Level ◽  
Biological Significance ◽  
C2c12 Cells ◽  
Myoblast Differentiation ◽  
C2c12 Myoblast ◽  
Mrna Levels ◽  
Transfected Cells ◽  
Myosin Heavy Chain Isoform ◽  
Important Mediator

AbstractPGC-1α has been implicated as an important mediator of functional capacity of skeletal muscle. However, the role of PGC-1α in myoblast differentiation remains unexplored. In the present study, we observed a significant up-regulation of PGC-1α expression during the differentiation of murine C2C12 myoblast. To understand the biological significance of PGC-1α up-regulation in myoblast differentiation, C2C12 cells were transfected with murine PGC-1α cDNA and siRNA targeting PGC-1α, respectively. PGC-1α over-expressing clones fused to form typical myotubes with higher mRNA level of myosin heavy chain isoform I (MyHCI) and lower MyHCIIX. No obvious differentiation was observed in PGC-1α-targeted siRNA-transfected cells with marked decrement of mRNA levels of MyHCI and MyHCIIX. Furthermore, PGC-1α increased the expression of MyoD and MyoG in C2C12 cells, which controlled the commitment of precursor cells to myotubes. These results indicate that PGC-1α is associated with myoblast differentiation and elevates MyoD and MyoG expression levels in C2C12 cells.

Role of nuclear receptors and hepatocyte-enriched transcription factors for Ntcp repression in biliary obstruction in mouse liver

2005 ◽  
Vol 289 (5) ◽  
pp. G798-G805 ◽  
Author(s):  
Gernot Zollner ◽  
Martin Wagner ◽  
Peter Fickert ◽  
Andreas Geier ◽  
Andrea Fuchsbichler ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Bile Acid ◽  
Dna Binding ◽  
Nuclear Receptors ◽  
Farnesoid X Receptor ◽  
Acid Uptake ◽  
Mrna Levels ◽  
Uptake System ◽  
Duct Ligation

Expression of the main hepatic bile acid uptake system, the Na+-taurocholate cotransporter (Ntcp), is downregulated during cholestasis. Bile acid-induced, farnesoid X receptor (FXR)-mediated induction of the nuclear repressor short heterodimer partner (SHP) has been proposed as a key mechanism reducing Ntcp expression. However, the role of FXR and SHP or other nuclear receptors and hepatocyte-enriched transcription factors in mediating Ntcp repression in obstructive cholestasis is unclear. FXR knockout (FXR−/−) and wild-type (FXR+/+) mice were subjected to common bile duct ligation (CBDL). Cholic acid (CA)-fed and LPS-treated FXR−/− and FXR+/+ mice were studied for comparison. mRNA levels of Ntcp and SHP and nuclear protein levels of hepatocyte nuclear factor (HNF)-1α, HNF-3β, HNF-4α, retinoid X receptor (RXR)-α, and retinoic acid receptor (RAR)-α and their DNA binding were assessed. Hepatic cytokine mRNA levels were also measured. CBDL and CA led to Ntcp repression in FXR+/+, but not FXR−/−, mice, whereas LPS reduced Ntcp expression in both genotypes. CBDL and LPS but not CA induced cytokine expression and reduced levels of HNF-1α, HNF-3β, HNF-4α, RXRα, and RARα to similar extents in FXR+/+ and FXR−/−. DNA binding of these transactivators was unaffected by CA in FXR+/+ mice but was markedly reduced in FXR−/− mice. In conclusion, Ntcp repression by CBDL and CA is mediated by accumulating bile acids via FXR and does not depend on cytokines, whereas Ntcp repression by LPS is independent of FXR. Reduced levels of HNF-1α, RXRα, and RARα in CBDL FXR−/− mice and reduced DNA binding in CA-fed FXR−/− mice, despite unchanged Ntcp levels, indicate that these factors may have a minor role in regulation of mouse Ntcp during cholestasis.

miR-369-3p serves as prognostic factor and regulates cancer progression of hepatocellular carcinoma

2021 ◽  
Author(s):  
Can Chen ◽  
Yi Zong ◽  
Jiaojiao Tang ◽  
Ruisheng Ke ◽  
Lizhi Lv ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Cancer Progression ◽  
Cell Counting ◽  
Migration And Invasion ◽  
Pcr Analysis ◽  
Reverse Transcription Pcr ◽  
Huh7 Cells

Background: The aim of this study was to investigate the role of miR-369-3p in hepatocellular carcinoma (HCC). Materials & methods: The expression levels of miR-369-3p were detected using the quantitative real-time reverse transcription-PCR analysis. The cell counting kit-8 and transwell assays were used to explore the effects of miR-369-3p on cell proliferation, migration and invasion of HCC cells. Results: The miR-369-3p expression was downregulated in HCC tissues and cell lines, in comparison to the normal controls, respectively. In vitro, overexpression of miR-369-3p in Hep 3B and Huh7 cells inhibited cell proliferation, migration and invasion. SOX4 was a direct target of miR-369-3p. Conclusion: Our results suggested that miR-369-3p may be a tumor suppressor in HCC by targeting SOX4.

scholarly journals DHX37 Impacts Prognosis of Hepatocellular Carcinoma and Lung Adenocarcinoma through Immune Infiltration

2020 ◽  
Vol 2020 ◽  
pp. 1-20
Author(s):  
Yanni Xu ◽  
Qiongchao Jiang ◽  
Hejun Liu ◽  
Xiaoyun Xiao ◽  
Dinghong Yang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
T Cell ◽  
Lung Adenocarcinoma ◽  
Immune Tolerance ◽  
Prognostic Value ◽  
Complex Function ◽  
T Cell Exhaustion ◽  
Rna Helicases ◽  
Cell Exhaustion

Background. RNA helicases have various essential functions in basically all aspects of RNA metabolism, not only unwinding RNA but also disturbing the interaction of RNA with proteins. Recently, RNA helicases have been considered potential targets in cancers. So far, there has been no detailed investigation of the biological functions of RNA helicase DHX37 in cancers. Objective. We aim to identify the prognostic value of DHX37 associated with tumor microenvironments in cancers. Methods. DHX37 expression was examined via the Oncomine database and Tumor Immune Estimation Resource (TIMER). We explored the prognostic role of DHX37 in cancers across various databases. Coexpression genes, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), and fundamental regulators were performed via LinkedOmics. Confirming the prognostic value of DHX37 in liver hepatocellular carcinoma (LIHC) and lung adenocarcinoma (LUAD), we explored the role of DHX37 in infiltrated lymphocytes in cancers using the Gene Expression Profiling Interactive Analysis (GEPIA) and TIMER databases. Results. Through GO and KEGG analyses, expression of DHX37 was also correlated with complex function-specific networks involving the ribosome and RNA metabolic signaling pathways. In LIHC and LUAD, DHX37 expression showed significant positive correlations with markers of Tregs, myeloid-derived suppressor cells (MDSCs), and T cell exhaustion, contributing to immune tolerance. Conclusion. These results indicate that DHX37 can serve as a prognostic biomarker in LIHC and LUAD while having an important role in immune tolerance by activating the function of Tregs, MDSC, and T cell exhaustion.

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