scholarly journals Identification of the hub gene BUB1B in hepatocellular carcinoma via bioinformatic analysis and in vitro experiments

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e10943
Author(s):  
Jie Fu ◽  
Xiao Zhang ◽  
Likun Yan ◽  
Yaoli Shao ◽  
Xinxu Liu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Hepatocellular Carcinoma ◽  
Genetic Alterations ◽  
Therapeutic Effects ◽  
In Vitro Experiments ◽  
Hub Genes ◽  
Post Surgery ◽  
Mitochondrial Functions

Background Hepatocellular carcinoma (HCC) is one of the most commonly diagnosed cancers and the fourth leading cause of cancer-related deaths in the world. Although the treatment of HCC has made great progress in recent years, the therapeutic effects on HCC are still unsatisfactory due to difficulty in early diagnosis, chemoresistance and high recurrence rate post-surgery. Methods In this study, we identified differentially expressed genes (DEGs) based on four Gene Expression Omnibus (GEO) datasets (GSE45267, GSE98383, GSE101685 and GSE112790) between HCC and normal hepatic tissues. A protein–protein interaction (PPI) network was established to identify the central nodes associated with HCC. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of the central nodes were conducted to find the hub genes. The expression levels of the hub genes were validated based on the ONCOMINE and Gene Expression Profiling Interactive Analysis (GEPIA) databases. Additionally, the genetic alterations of the hub genes were evaluated by cBioPortal. The role of the hub genes on the overall survival (OS) and relapse survival (RFS) of HCC patients was evaluated by Kaplan-Meier plotter. At last, the mechanistic role of the hub genes was illustrated by in vitro experiments. Results We found the following seven hub genes: BUB1B, CCNB1, CCNB2, CDC20, CDK1, MAD2L1 and RRM2 using integrated bioinformatics analysis. All of the hub genes were significantly upregulated in HCC tissues. And the seven hub genes were associated with the OS and RFS of HCC patients. Finally, in vitro experiments indicated that BUB1B played roles in HCC cell proliferation, migration, invasion, apoptosis and cell cycle by partially affecting mitochondrial functions. Conclusions In summary, we identified seven hub genes that were associated with the expression and prognosis of HCC. The mechanistic oncogenic role of BUB1B in HCC was first illustrated. BUB1B might play an important role in HCC and could be potential therapeutic targets for HCC.

scholarly journals Comprehensive analysis of abnormal expression, prognostic value and oncogenic role of the hub gene FN1 in pancreatic ductal adenocarcinoma via bioinformatic analysis and in vitro experiments

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e12141
Author(s):  
Xiaohua Lei ◽  
Guodong Chen ◽  
Jiangtao Li ◽  
Wu Wen ◽  
Jian Gong ◽  
...  
Keyword(s):  
Gene Expression ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Bioinformatic Analysis ◽  
Ductal Adenocarcinoma ◽  
Therapeutic Effects ◽  
Hub Genes ◽  
Poor Overall Survival ◽  
Geo Dataset

Background Pancreatic ductal adenocarcinoma (PDAC) is one of the most commonly diagnosed cancers with a poor prognosis worldwide. Although the treatment of PDAC has made great progress in recent years, the therapeutic effects are still unsatisfactory. Methods. In this study, we identified differentially expressed genes (DEGs) between PDAC and normal pancreatic tissues based on four Gene Expression Omnibus (GEO) datasets (GSE15471, GSE16515, GSE28735 and GSE71729). A protein–protein interaction (PPI) network was established to evaluate the relationship between the DEGs and to screen hub genes. The expression levels of the hub genes were further validated through the Gene Expression Profiling Interactive Analysis (GEPIA), ONCOMINE and Human Protein Atlas (HPA) databases, as well as the validation GEO dataset GSE62452. Additionally, the prognostic values of the hub genes were evaluated by Kaplan–Meier plotter and the validation GEO dataset GSE62452. Finally, the mechanistic roles of the most remarkable hub genes in PDAC were examined through in vitro experiments. Results We identified the following nine hub genes by performing an integrated bioinformatics analysis: COL1A1, COL1A2, FN1, ITGA2, KRT19, LCN2, MMP9, MUC1 and VCAN. All of the hub genes were significantly upregulated in PDAC tissues compared with normal pancreatic tissues. Two hub genes (FN1 and ITGA2) were associated with poor overall survival (OS) rates in PDAC patients. Finally, in vitro experiments indicated that FN1 plays vital roles in PDAC cell proliferation, colony formation, apoptosis and the cell cycle. Conclusions In summary, we identified two hub genes that are associated with the expression and prognosis of PDAC. The oncogenic role of FN1 in PDAC was first illustrated by performing an integrated bioinformatic analysis and in vitro experiments. Our results provide a fundamental contribution for further research aimed finding novel therapeutic targets for overcoming PDAC.

scholarly journals Tamoxifen protects breast cancer patients from COVID-19: first evidence from real world data

2021 ◽  
Author(s):  
Sara Bravaccini ◽  
Fabio Nicolini ◽  
William Balzi ◽  
Irene Azzali ◽  
Arianna Calistri ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Protective Role ◽  
In Vitro Experiments ◽  
Breast Cancer Patients ◽  
Real World Data ◽  
17Β Estradiol ◽  
Hormonal Therapies

Abstract Background COVID-19 severity is uneven between genders. We hypothesized a role of hormonal therapies in the severity of COVID-19 in breast cancer (BC) patients via the modulation of SARS-CoV-2 susceptibility genes. Patients and Methods We mined the Emilia Romagna region (Italy) registries to compare the rates of hospitalization and mortality for COVID-19 in 2020 amongst 24628 BC patients. Next, we analyzed the modulation of ACE2, TMPRSS2 and NRP1 gene expression and the susceptibility to SARS-CoV-2 infection by tamoxifen, fulvestrant and 17β-estradiol on human ER+ MCF-7 cells in vitro.Results The hospitalization rate observed for 4784 tamoxifen treated BC patients was the lowest (OR, 0.41; 95% CI, 0.18-0.94; p=0.04) among hormonal therapies and no fatalities occurred. A standard mortality rate reduction has been observed also for patients treated with aromatase inhibitors (SMR: 0.73; 95% CI, 0.45-0.90). In vitro experiments showed that fulvestrant, but not tamoxifen, increases ACE2, TMPRSS2 and NRP1 gene expression and susceptibility to SARS-CoV-2 infection and that 17β-estradiol reduces significantly TMPRSS2 and NRP1 expression.Conclusions Tamoxifen treated BC patients showed a reduced rate of hospitalization and strikingly no fatalities for COVID-19. In vitro experiments confirmed a protective role of tamoxifen while an increased susceptibility to SARS-CoV-2 infection of ER+ cells treated with fulvestrant was observed.

scholarly journals Screening Hub Genes as Prognostic Biomarkers of Hepatocellular Carcinoma by Bioinformatics Analysis

2019 ◽  
Vol 28 (1_suppl) ◽  
pp. 76S-86S ◽  
Author(s):  
Zengyuan Zhou ◽  
Yuzheng Li ◽  
Haiyue Hao ◽  
Yuanyuan Wang ◽  
Zihao Zhou ◽  
...  
Keyword(s):  
Gene Expression ◽  
Hepatocellular Carcinoma ◽  
Expression Profiles ◽  
Gene Expression Omnibus ◽  
Prognostic Biomarkers ◽  
Ppi Network ◽  
Hub Genes ◽  
P53 Signaling

Hepatocellular carcinoma (HCC) is a widespread, common type of cancer in Asian countries, and the need for biomarker-matched molecularly targeted therapy for HCC has been increasingly recognized. However, the effective treatment for HCC is unclear. Therefore, identifying additional hub genes and pathways as novel prognostic biomarkers for HCC is necessary. In this study, the expression profiles of GSE121248, GSE45267 and GSE84402 were obtained from the Gene Expression Omnibus (GEO), including 132 HCC and 90 noncancerous liver tissues. Differentially expressed genes (DEGs) between HCC and noncancerous samples were identified by GEO2 R and Venn diagrams. In total, 109 DEGs were identified in these datasets, including 24 upregulated genes and 85 downregulated genes. Subsequently, Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) preliminary analyses of the DEGs were performed using DAVID. The protein–protein interaction (PPI) network of the DEGs was constructed with the Search Tool for the Retrieval of Interacting Genes (STRING) and visualized in Cytoscape. Module analysis of the PPI network was performed using MCODE to get hub genes. Moreover, the influence of the hub genes on overall survival was determined with Kaplan–Meier plotter. All hub genes were analyzed by Gene Expression Profiling Interactive Analysis (GEPIA) and KEGG. Overall, the hub genes DTL, CDK1, CCNB1, RACGAP1, ECT2, NEK2, BUB1B, PBK, TOP2A, ASPM, HMMR, RRM2, CDKN3, PRC1, and ANLN were upregulated in HCC, and the survival rate was lower for HCC with increased expression of these hub genes. CCNB1, CDK1, and RRM2 were enriched in the p53 signaling pathway, and CCNB1, CDK1, and BUB1B were enriched in the cell cycle. In brief, we screened 15 hub genes and pathways to identify potential prognostic markers for HCC treatment. However, the specific occurrence and development of HCC with expression of the hub genes should be verified in vivo and in vitro.

scholarly journals Identification of genes in hepatocellular carcinoma induced by non-alcoholic fatty liver disease

2020 ◽  
Vol 29 (1) ◽  
pp. 69-78
Author(s):  
Changzhou Cai ◽  
Xin Song ◽  
Chaohui Yu
Keyword(s):  
Gene Expression ◽  
Hepatocellular Carcinoma ◽  
Functional Enrichment ◽  
Hub Genes ◽  
Alcoholic Fatty Liver ◽  
Protein Protein Interaction ◽  
Pathogenic Genes ◽  
Search Tool ◽  
Expression Microarrays

BACKGROUND: Hepatocellular carcinoma (HCC) is the leading cause of mortality worldwide. In recent years, the incidence of HCC induced by NAFLD is growing rapidly. OBJECTIVE: To screen for new pathogenic genes and related pathways both in NAFLD and HCC, and to explore the pathogenesis of progression from NAFLD to HCC. METHODS: Gene expression microarrays (GSE74656, GSE62232) were used for identifying differentially expressed genes (DEGs). Functional enrichment and pathway enrichment analyses indicated that these DEGs were related to cell cycle and extracellular exosome, which were closely related to NAFLD and HCC development. We then used the Search Tool for the Retrieval of Interacting Genes (STRING) to establish the protein-protein interaction (PPI) network and visualized them in Cytoscape. And the overall survival (OS) analysis and gene expression validation in TCGA of hub genes was performed. RESULTS: Seven hub genes, including CDK1, HSP90AA1, MAD2L1, PRKCD, ITGB3BP, CEP192, and RHOB were identified. Finally, we verified the expression level of ITGB3BP and CEP192 by quantitative real-time PCR in vitro. CONCLUSIONS: The present study implied possible DEGs, especially the new gene CEP192, in the progression of NAFLD developing to HCC. Further rigorous experiments are required to verify the above results.

Prognostic significance and function of MCM10 in human hepatocellular carcinoma

2021 ◽  
Author(s):  
Yi-Ru Chen ◽  
Yi-Ting Li ◽  
Mei-Qian Wang ◽  
Sen-Lin Zhu
Keyword(s):  
Hepatocellular Carcinoma ◽  
Characteristic Curve ◽  
Prognostic Significance ◽  
Prognostic Indicator ◽  
Genetic Alterations ◽  
The Cancer Genome Atlas ◽  
Prognostic Accuracy ◽  
Tumor Node Metastasis Stage

Aim: To investigate the role of MCM10, a conserved replication factor, in hepatocellular carcinoma (HCC). Methods: We used data from 364 HCC patients in the Cancer Genome Atlas database and conducted in vitro experiments to confirm the role of MCM10. Results: High MCM10 expression correlated with poor HCC patient outcome and was an independent prognosticator for HCC. Time-dependent receiver operating characteristic curve analysis found that the sequential trend of MCM10 for survival was not inferior to that of the tumor node metastasis stage. The MCM10 model had a higher C-index than the non- MCM10 model, indicating that incorporating MCM10 into a multivariate model improves the model’s prognostic accuracy for HCC. Genetic alterations of MCM10 prominently correlated with an unfavorable HCC outcome. Conclusion: Our findings strongly suggest using the MCM10 gene as a prognostic indicator in HCC.

Accumulation of AGO2 facilitates tumor proliferation and metastasis through upregulating Survivin, Vimentin and Snail in human hepatocellular carcinoma

2019 ◽  
Author(s):  
Yang Yang ◽  
Qi Mei
Keyword(s):  
Gene Expression ◽  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Xenograft Model ◽  
Proliferation And Metastasis ◽  
Interfering Rna ◽  
Cell Proliferation And Metastasis

Abstract Background：Argonaute 2 (AGO2), a typical member of the Ago gene family, plays a pivotal role in hepatocellular carcinoma (HCC) tumorgenesis through regulating the short interfering RNA-mediated gene silencing. However, the underlined mechanism needs clarified. Herein, we found that AGO2 was frequently upregulated in human HCC cancerous tissues compared with non-cancerous tissues. Methods: Clinical analyses were performed to determine the relation between the expression level of AGO2 and prognosis in HCC patients. By using CRISPR/Cas9 approach in SMMC-7721 cells and establishing xenograft model in nude mice, we further identified the role of AGO2 in HCC. Gene expression microarray analysis was used to reveal the changes of gene expression profile mediated by AGO2 depletion in SMMC-7721 cells. Results: We observed that the overexpression of AGO2 was associated with poor prognosis in HCC patients. The knockout of AGO2 inhibited tumor cell proliferation and metastasis in vivo and in vitro. We also identified that AGO2 facilitates HCC tumorigenesis through modulating Survivin, Vimentin and Snail expression. Conclusions: Therefore, this study not only demonstrates that accumulation of AGO2 promotes cell proliferation and metastasis in HCC, but also provides a novel molecular mechanism in HCC progression.

scholarly journals Possible Role of IRS-4 in the Origin of Multifocal Hepatocellular Carcinoma

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2560
Author(s):  
Luis G. Guijarro ◽  
Patricia Sanmartin-Salinas ◽  
Eva Pérez-Cuevas ◽  
M. Val Toledo-Lobo ◽  
Jorge Monserrat ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cancer ◽  
Hepg2 Cells ◽  
Cellular Polarity ◽  
Ki 67 ◽  
Tissue Samples ◽  
Vitro Analysis ◽  
Tumoral Cells

New evidence suggests that insulin receptor substrate 4 (IRS-4) may play an important role in the promotion of tumoral growth. In this investigation, we have evaluated the role of IRS-4 in a pilot study performed on patients with liver cancer. We used immunohistochemistry to examine IRS-4 expression in biopsies of tumoral tissue from a cohort of 31 patient suffering of hepatocellular carcinoma (HCC). We simultaneously analyzed the expression of the cancer biomarkers PCNA, Ki-67, and pH3 in the same tissue samples. The in vitro analysis was conducted by studying the behavior of HepG2 cells following IRS-4 overexpression/silencing. IRS-4 was expressed mainly in the nuclei of tumoral cells from HCC patients. In contrast, in healthy cells involved in portal triads, canaliculi, and parenchymal tissue, IRS-4 was observed in the cytosol and the membrane. Nuclear IRS-4 in the tumoral region was found in 69.9 ± 3.2%, whereas in the surrounding healthy hepatocytes, nuclear IRS-4 was rarely observed. The percentage of tumoral cells that exhibited nuclear PCNA and Ki-67 were 52.1 ± 7%, 6.1 ± 1.1% and 1.3 ± 0.2%, respectively. Furthermore, we observed a significant positive linear correlation between nuclear IRS-4 and PCNA (r = 0.989; p < 0.001). However, when we correlated the nuclear expression of IRS-4 and Ki-67, we observed a significant positive curvilinear correlation (r = 0.758; p < 0.010). This allowed us to define two populations, (IRS-4 + Ki-67 ≤ 69%) and (IRS-4 + Ki-67 > 70%). The population with lower levels of IRS-4 and Ki-67 had a higher risk of suffering from multifocal liver cancer (OR = 16.66; CI = 1.68–164.8 (95%); p < 0.05). Immunoblot analyses showed that IRS-4 in normal human liver biopsies was lower than in HepG2, Huh7, and Chang cells. Treatment of HepG2 with IGF-1 and EGF induced IRS-4 translocation to the nucleus. Regulation of IRS-4 levels via HepG2 transfection experiments revealed the protein’s role in proliferation, cell migration, and cell-collagen adhesion. Nuclear IRS-4 is increased in the tumoral region of HCC. IRS-4 and Ki-67 levels are significantly correlated with the presence of multifocal HCC. Moreover, upregulation of IRS-4 in HepG2 cells induced proliferation by a β-catenin/Rb/cyclin D mechanism, whereas downregulation of IRS-4 caused a loss in cellular polarity and in its adherence to collagen as well as a gain in migratory and invasive capacities, probably via an integrin α2 and focal adhesion cascade (FAK) mechanism.

Knockout of Ajuba Attenuates the Growth and Migration of Hepatocellular Carcinoma Cells

2020 ◽  
Vol 160 (11-12) ◽  
pp. 650-658
Author(s):  
Yichen Le ◽  
Yi He ◽  
Meirong Bai ◽  
Ying Wang ◽  
Jiaxue Wu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Growth ◽  
Cancer Progression ◽  
Normal Liver ◽  
Cell Growth And Migration ◽  
And Migration ◽  
Hcc Cells

Ajuba has been found to be mutated or aberrantly regulated in several human cancers and plays important roles in cancer progression via different signaling pathways. However, little is known about the role of Ajuba in hepatocellular carcinoma (HCC). Here, we found an upregulation of Ajuba expression in HCC tissues compared with normal liver tissues, while a poor prognosis was observed in HCC patients with high Ajuba expression. Knockout of Ajuba in HCC cells inhibited cell growth in vitro and in vivo, suppressed cell migration, and enhanced the cell apoptosis under stress. Moreover, re-expression of Ajuba in Ajuba-deficient cells could restore the phenotype of Ajuba-deficient cells. In conclusion, these results indicate that Ajuba is upregulated in HCC and promotes cell growth and migration of HCC cells, suggesting that Ajuba could possibly be a new target for HCC diagnosis and treatment.

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