scholarly journals Identification of molecular target genes and key pathways in hepatocellular carcinoma by bioinformatics analysis

2018 ◽  
Vol Volume 11 ◽  
pp. 1861-1869 ◽  
Author(s):  
Lei Zhou ◽  
Yanyan Du ◽  
Lingqun Kong ◽  
Xingyuan Zhang ◽  
Qiangpu Chen
2019 ◽  
Author(s):  
Hao Xing ◽  
Jin Zhang ◽  
Kai-Lian Zheng ◽  
Ming-Da Wang ◽  
Jun Han ◽  
...  

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.


2018 ◽  
Vol 47 (1) ◽  
pp. 383-390 ◽  
Author(s):  
Yu Zhu ◽  
Chengmao Zhou ◽  
Qixiong He

Objective To observe the expression and clinical significance of micro RNA (miR)-139-3p in liver cancer tissues, and to explore its relationship with miR-139-3p target genes related to the prognosis of hepatocellular carcinoma (HCC). Methods A total of 362 patients with HCC were included in the study. Liver hepatocellular carcinoma data were obtained directly from The Cancer Genome Atlas data portal .The bioinformatics analysis tool TargetScan was applied to predict miR-139-3p target genes. Results Survival time was significantly higher in patients with high miR-139-3p expression, compared with the low miR-139-3p expression group. Bioinformatics analysis showed that miR-139-3p target genes ISG20L2, RAD54B, KIAA0101, and PIGS were significantly negatively correlated with miR-139-3p expression. Conclusions High miR-139-3p expression in HCC tissues was indicative of good patient prognosis. miR-139-3p target genes ISG20L2, RAD54B, KIAA0101, and PIGS were related to HCC prognosis.


2019 ◽  
Vol Volume 12 ◽  
pp. 5153-5162
Author(s):  
Junxue Tu ◽  
Jingjing Chen ◽  
Meimei He ◽  
Hongfei Tong ◽  
Haibin Liu ◽  
...  

2020 ◽  
Author(s):  
Jankun Liu ◽  
zy liu ◽  
Wei Li ◽  
Xinghua Pan ◽  
Zongjiang Fan ◽  
...  

Abstract Background Hepatocellular carcinoma (HCC) is a malignancy causing highly death rate in the world. Despite the development of treatment strategies for HCC, prognosis of this malignancy remains unsatisfactory. In this study, we aimed to identify the target genes associated with the prognosis of HCC patients. Methods Three expression profiles of HCC tissues were extracted from the Gene Expression Omnibus database to explore the differentially expressed genes (DEGs) using GEO2R method. Functional enrichment analysis was performed to reveal the biological characteristics of DEGs. Protein-protein interaction (PPI) network was constructed using Cytoscape software. The survival curve of identified DEGs were tested by Kaplan-Meier analysis. Results We identified 15 DEGs (CYP39A1, CYR61, FOS, FOXO1, GADD45B, ID1, IL1RAP, MT1M, PHLDA1, RND3, SDS, SOCS2, TAT, S100P, and SPINK1) in HCC tissues. Prognosis analysis showed that 4 DEGs (FOXO1,SPINK1༌SOCS2, and TAT) correlated with overall survival time of HCC patients, which might serve as therapeutic targets for HCC patients. Conclusions By integrated bioinformatics analysis, we proposed a novel way to reveal key genes that closely relate to HCC development.


2020 ◽  
Vol 15 ◽  
Author(s):  
Na Wang ◽  
Yukun Li ◽  
Sijing Liu ◽  
Liu Gao ◽  
Chang Liu ◽  
...  

Background: Recent studies revealed that the hypoglycemic hormone, glucagon-like peptide-1 (GLP-1), acted as an important modulator in osteogenesis of bone marrow derived mesenchymal stem cells (BMSCs). Objectives: The aim of this study was to identify the specific microRNA (miRNA) using bioinformatics analysis and validate the presence of differentially expressed microRNAs with their target genes after GLP-1 receptor agonist (GLP-1RA) administration involved in ostogenesis of BMSCs. Methods: MiRNAs were extracted from BMSCs after 5 days’ treatment and sent for high-throughput sequencing for differentially expressed (DE) miRNAs analyses. Then the expression of the DE miRNAs verified by the real-time RT-PCR analyses. Target genes were predicted, and highly enriched GOs and KEGG pathway analysis were conducted using bioinformatics analysis. For the functional study, two of the target genes, SRY (sex determining region Y)-box 5 (SOX5) and G protein-coupled receptor 84 (GPR84), were identified. Results: A total of 5 miRNAs (miRNA-509-5p, miRNA-547-3p, miRNA-201-3p, miRNA-201-5p, and miRNA-novel-272-mature) were identified differentially expressed among groups. The expression of miRNA-novel-272-mature were decreased during the osteogenic differentiation of BMSCs, and GLP-1RA further decreased its expression. MiRNA-novel-272-mature might interact with its target mRNAs to enhance osteogenesis. The lower expression of miRNA-novel-272-mature led to an increase in SOX5 and a decrease in GPR84 mRNA expression, respectively. Conclusions: Taken together, these results provide further insights to the pharmacological properties of GLP-1RA and expand our knowledge on the role of miRNAs-mRNAs regulation network in BMSCs’ differentiation.


BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jian-Yao Wang ◽  
Xiang-Kun Wang ◽  
Guang-Zhi Zhu ◽  
Xin Zhou ◽  
Jun Yao ◽  
...  

Abstract Backgroud In our current work, we aimed to investigate the expressions of glypican (GPC) family genes at the mRNA level and assess their prognostic significances in patients with hepatocellular carcinoma (HCC). Methods The pathological roles of GPC family genes were examined using bioinformatics analysis. The diagnostic values of GPC genes were explored with the Gene Expression Profiling Interactive Analysis. Moreover, the mRNA expression and prognostic values of GPC genes were assessed via the KM plotter database. Results Our data showed that the expression of GPC-3 was dramatically increased in the liver tumor tissue. Moreover, the expressions of the other five GPC family members were not significantly different between the tumor and normal liver tissues (P > 0.05). Furthermore, the up-regulation of GPC-1 at the mRNA level was dramatically correlated to the reduced overall survival (OS) for all HCC patients (hazard ratio = 2.03, 95% confidence intervals =1.44–2.87, P = 4.1e-05) compared with its low-expression group. Besides, the prognosis of the Caucasians was related to most GPC family genes, while the prognosis of the Asian race was only related to the expression of GPC-2. Besides, for pathological factors, including stage, grade, AJCC, and vascular invasion, the higher the pathological grade and vascular invasiveness, the lower the expression levels of GPC family genes (P < 0.05). Finally, the expression levels of GPC-1, 2, and 3 in the hepatitis group were related to the poor prognosis of HCC in the risk factor (alcohol consumption and hepatitis) subgroup (P < 0.05). Conclusions Our findings indicated that GPC-3 was dysregulated in HCC compared with paracancerous tissues. The expression of GPC-1 could be used as a potent predictive index for the general prognosis of HCC. The pathology, patients, and risk factors might affect the prognostic value of GPC family genes in HCC.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Xiaoxi Fan ◽  
Zhongwei Zhao ◽  
Jingjing Song ◽  
Dengke Zhang ◽  
Fazong Wu ◽  
...  

Abstract Background Accumulating evidences have been reported that long noncoding RNAs play crucial roles in the progression of hepatocellular carcinoma (HCC). SnoRNA host gene 6 (SNHG6) is believed to be involved in several human cancers, but the specific molecular mechanism of SNHG6 in HCC is not well studied. Methods In this study, we experimentally down-regulated the SNHG6 in two hepatocellular carcinoma cell lines in vitro, and then measured the proliferation, migration and invasion abilities and the apoptotic levels. Also, we performed the xenograft assay to investigate the function of SNHG6 during the tumor growth in vivo. Results We found SNHG6 was highly expressed in HCC tissues. Next, using Hep3B and Huh7 cells, we confirmed knockdown of SNHG6 reduced the proliferation, migration and invasion abilities in vitro. Also, by bioinformatics analysis, further molecular and cellular experiments, we found miR-6509-5p bound to SNHG6 directly, and the expression level of HIF1A was regulated through SNHG6/miR-6509-5p axis. Finally, we found that down-regulation of SNHG6 dramatically reduced the tumor growth ability of Huh7 cells in vivo. Conclusions We concluded that SNHG6/miR-6509-5p/HIF1A axis functioned in the progression of hepatocellular carcinoma, and could be the promising therapeutic targets during the development of hepatocellular carcinoma drugs.


2021 ◽  
Author(s):  
Tingdan Zheng ◽  
Wuqi Song ◽  
Aiying Yang

Abstract Objective Here we performed the Bioinformatics analysis on the data from The Cancer Genome Atlas (TCGA), in order to find the correlation between the expression of ATP Binding Cassette (ABC) Transporters’ genes and hepatocellular carcinoma (HCC) prognosis; Methods Transcriptome profiles and clinical data of HCC were obtained from TCGA database. Package edgeR was used to analyze differential gene expression. Patients were divided into low-ABC expression and high-ABC expression groups based on the median expression level of ABC genes in cancer. The overall survival and short-term survival (n= 341) of the two groups was analyzed using the log-rank test and Wilcoxon test; Results We found that ABC gene expression was correlated with the expression of PIK3C2B (p<0.001, ABCC1: r=0.27; ABCC10: r=0.57; ABCC4: r=0.20; ABCC5: r=0.28; ABCB9: r=0.17; ABCD1: r=0.21). All patients with low-ABC expression showed significantly increased overall survival. Significantly decreased overall survival (Log-rank test: p<0.05, Wilcoxon test: p<0.05) was found in patients with high expression of ABCC1 (HR=1.58), ABCD1 (HR=1.45), ABCC4 (HR=1.56), and ABCC5 (HR=1.64), while decreased short-term survival (Log-rank test: p>0.05, Wilcoxon test: p<0.05) was correlated with the increased expression of ABCC10 (HR=1.29), PIK3C2B (HR=1.29) and ABCB9 (HR=1.23); Conclusions Our findings indicate that the specific ABC gene expression correlates with the prognosis of HCC. Therefore, ABC expression profile could be a potential indicator for HCC patients.


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