scholarly journals Functional lncRNA-miRNA-mRNA Networks in Response to Baicalein Treatment in Hepatocellular Carcinoma

2021 ◽  
Vol 2021 ◽  
pp. 1-18
Author(s):  
Xin Zhao ◽  
Dongyang Tang ◽  
Xiaofei Chen ◽  
Shaoqing Chen ◽  
Cheng Wang
Keyword(s):  
Hepatocellular Carcinoma ◽  
Treatment Group ◽  
Cancer Progression ◽  
Messenger Rna ◽  
Noncoding Rna ◽  
Mirna Targets ◽  
Kaplan Meier ◽  
Dmso Treatment ◽  
Human Protein Atlas ◽  
Kaplan Meier Plotter

Introduction. Baicalein has been shown to have antitumor activities in several cancer types. However, its acting mechanisms remain to be further investigated. This work is aimed at exploring the functional long noncoding RNA (lncRNA)/microRNA (miRNA)/messenger RNA (mRNA) triplets in response to baicalein in hepatocellular carcinoma (HCC) cell to understand the mechanisms of baicalein in HCC. Methods. Differentially expressed lncRNAs (DELs) and miRNAs (DEMs) in HCC cell treated with baicalein were first screened using GSE95504 and GSE85511, respectively. miRNA targets for DELs were predicted and intersected with DEMs, after which the miRNA expression was validated using ENCORI and its prognostic value was assessed using Kaplan-Meier plotter. Potential miRNA targets were predicted by 3 prediction tools, after which expression level was validated at UALCAN and Human Protein Atlas. Kaplan-Meier plotter was used to evaluate the effects of these genes on overall survival and recurrence-free survival of HCC patients. Enrichment analyses for these genes were performed at DAVID. Results. Here, we identified 14 overlapping DELs and 26 overlapping DEMs in the baicalein treatment group than those in the DMSO treatment group. Subsequently, by analyzing expression and clinical significance of miRNAs, hsa-miR-4443 was found as a highly potential miRNA target. Then, targets of hsa-miR-4443 were predicted and analyzed, and we found AKT1 was the most potential target for hsa-miR-4443. Hence, the lncRNAs-hsa-miR-4443-AKT1 axis that can respond to baicalein was established. Conclusion. Collectively, we elucidated a role of lncRNAs-hsa-miR-4443-AKT1 pathway in response to baicalein treatment in HCC, which could help us understand the roles of baicalein in inhibiting cancer progression and may provide novel insights into the mechanisms behind HCC progression.

scholarly journals Expression and prognostic roles of PRDXs gene family in hepatocellular carcinoma

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Mingxing Xu ◽  
Jianliang Xu ◽  
Dun Zhu ◽  
Rishun Su ◽  
Baoding Zhuang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Acid Metabolism ◽  
Family Members ◽  
Interaction Network ◽  
Genetic Alterations ◽  
Database Analysis ◽  
Kaplan Meier ◽  
Canonical Pathways ◽  
Human Protein Atlas ◽  
Kaplan Meier Plotter

Abstract Background As the fourth leading cause of cancer-related death in the world, the therapeutic effect and 5-year overall survival of hepatocellular carcinoma (HCC) are not optimistic. Previous researches indicated that the disorder of PRDXs was related to the occurrence and development of cancers. Methods In this study, PRDXs were found in various tumor cell lines by CCLE database analysis. The analysis results of UALCAN, HCCDB and Human Protein Atlas databases showed the expression of PRDXs mRNA and protein in HCC tissues was dysregulated. Besides, UALCAN was used to assess the correlations between PRDXs mRNA as well as methylation levels and clinical characterization. Results High expression of PRDX1 or low expression of PRDX2/3 suggested poor prognosis for HCC patients which was demonstrated by Kaplan–Meier Plotter. The genetic alterations and biological interaction network of PRDXs in HCC samples were obtained from c-Bioportal. In addition, LinkedOmics was employed to analyze PRDXs related differentially expressed genes, and on this basis, enrichment of KEGG pathway and miRNAs targets of PRDXs were conducted. The results indicated that these genes were involved in several canonical pathways and certain amino acid metabolism, some of which may effect on the progression of HCC. Conclusions In conclusion, the disordered expression of some PRDX family members was associated with the prognosis of HCC patients, suggesting that these PRDX family members may become new molecular targets for the treatment and prognosis prediction of HCC.

scholarly journals Up-regulated RFC2 Predicts Unfavorably Progression in Hepatocellular Carcinoma

2020 ◽  
Author(s):  
Zaixiong Ji ◽  
Jiaqi Li ◽  
Jianbo Wang
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cancer ◽  
Tumor Grade ◽  
Replication Factor C ◽  
Ppi Network ◽  
Protein Protein Interaction ◽  
Kaplan Meier ◽  
Human Protein Atlas ◽  
Factor C ◽  
Kaplan Meier Plotter

Abstract Background: Replication factor C (RFC) is closely related to tumor progression and metastasis. However, the functional significance of RFC2 in hepatocellular carcinoma remains unclear.Materials and methods: In order to solve this problem, the expression of RFC2 in liver cancer patients was analyzed through ONCOMINE, UALCAN, human protein atlas. Survival analysis was conducted using Kaplan-Meier plotter and GEPIA. GO and KEGG enrichment analyses were carried out. The protein-protein interaction (PPI) network was performed through Metascape.Result: The transcription and protein level of RFC2 in HCC were overexpressed, which was significantly related to the clinical individual cancer stage and pathological tumor grade of HCC patients. In addition, in patients with liver cancer, higher RFC2 expression was found to be significantly correlated with shorter OS and DFS. Furthermore, the function of RFC2 in liver cancer was DNA replication, and its main mechanism was the phase transition of the cell cycle.Conclusion: RFC2 might promote the development of liver cancer. It could also be used as a novel biomarker for the prognosis of liver cancer.

scholarly journals Identification of hub genes and potential drugs in hepatocellular carcinoma through integrated bioinformatics analysis

2020 ◽  
Author(s):  
Xiaolong Chen ◽  
Zhixiong Xia ◽  
Yafeng Wan ◽  
Ping Huang
Keyword(s):  
Hepatocellular Carcinoma ◽  
Disease Free Survival ◽  
Interaction Network ◽  
Enrichment Analysis ◽  
Hub Genes ◽  
Free Survival ◽  
Protein Protein Interaction ◽  
Kaplan Meier ◽  
Human Protein Atlas ◽  
Kaplan Meier Plotter

Abstract BackgroundHepatocellular carcinoma (HCC) is the third cancer-related cause of death in the world. Until now, the involved mechanisms during the development of HCC are largely unknown. This study aims to explore the driven-genes and potential drugs in HCC. MethodsThree mRNA expression datasets were used to analyze the differentially expressed genes (DEGs) in HCC. The bioinformatics approaches include identification of DEGs and hub genes, GO terms analysis and KEGG enrichment analysis, construction of protein–protein interaction network. The expression levels of hub genes were validated based on TCGA, GEPIA and the Human Protein Atlas. Moreover, overall survival and disease-free survival analysis of the hub genes were further conducted by Kaplan-Meier plotter and the GEPIA. DGIdb database was performed to search the candidate drugs for HCC. ResultsFinally, 197 DEGs were identified. The PPI network was constructed using STRING software. Then ten genes were selected and considered as the hub genes. The ten genes were all closely related to the survival of HCC patients. DGIdb database predicted 39 small molecules as the possible drugs for treating HCC. ConclusionsOur study provides some new insights into HCC pathogenesis and treatments. The candidate drugs may improve the efficiency of HCC therapy in future.

scholarly journals Expression and Prognostic Roles of PRDXs Gene Family in Hepatocellular Carcinoma

2020 ◽  
Author(s):  
Mingxing Xu ◽  
Jianliang Xu ◽  
Dun Zhu ◽  
Rishun Su ◽  
Baoding Zhuang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Acid Metabolism ◽  
Interaction Network ◽  
Public Database ◽  
Kaplan Meier ◽  
Online Tools ◽  
Canonical Pathways ◽  
Human Protein Atlas ◽  
Kaplan Meier Plotter ◽  
Analyze Data

Abstract Background: As the second leading cause of cancer-related death in the world, the therapeutic effect and 5-year overall survival of hepatocellular carcinoma (HCC) are not optimistic. Previous researches indicated that the disorder of PRDXs was related to the occurrence and development of cancer. Methods: In this study,analyzing through CCLE, UALCAN, HCCDB and Human Protein Atlas database databases, PRDXs not only existedin various tumor cell lines, but alsohad maladjusted expression on mRNA and protein levelsin HCC tissues. Besides, the correlations between mRNA as well as methylation levels of PRDXs and clinical characterization wereevaluated using UALCAN. Results: Kaplan-Meier Plotter demonstrated that high expression of PRDX1 or low expression of PRDX2/3 suggested poor prognosis for HCC patients. The mutation frequency, type and biological interaction network of PRDXs were obtained from c-Bioportal. By LinkedOmics,PRDXs related differential expressions geneswere obtained, which were involved in several canonical pathways and certain amino acid metabolism, as well as miRNAs targeting PRDXs, some of which may effect on the progression of HCC. Conclusions: In conclusion, using online tools to analyze data based on several public database, it was found that disordered expression of PRDXs was correlated with the prognosis of HCC patients, suggesting that PRDXs may be new molecular targets for HCC therapy and prognosis prediction.

scholarly journals Expression and prognostic roles PRDXs gene family in hepatocellular carcinoma

2020 ◽  
Author(s):  
Mingxing Xu ◽  
Jianliang Xu ◽  
Dun Zhu ◽  
Rishun Su ◽  
Baoding Zhuang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Acid Metabolism ◽  
Interaction Network ◽  
Tumor Cell Lines ◽  
Protein Levels ◽  
Kaplan Meier ◽  
Online Tools ◽  
Canonical Pathways ◽  
Human Protein Atlas ◽  
Kaplan Meier Plotter

Abstract Background: As the second leading cause of cancer-related death in the world, the therapeutic effect and 5-year overall survival of hepatocellular carcinoma (HCC) are not optimistic. Previous researches indicated that the disorder of PRDXs was related to the occurrence and development of cancer.Methods: In this study, analyzing through CCLE, UALCAN, HCCDB and Human Protein Atlas database databases, PRDXs not only existed in various tumor cell lines, but also had maladjusted expression on mRNA and protein levels in HCC tissues. Besides, the correlations between mRNA as well as methylation levels of PRDXs and clinical characterization were evaluated using UALCAN.Results: Kaplan-Meier Plotter demonstrated that high expression of PRDX1 or low expression of PRDX2/3 suggested poor prognosis for HCC patients. The mutation frequency, type and biological interaction network of PRDXs were obtained from c-Bioportal. By LinkedOmics, PRDXs related differential expressions genes were obtained, which were involved in several canonical pathways and certain amino acid metabolism, as well as miRNAs targeting PRDXs, some of which may effect on the progression of HCC.Conclusions: In conclusion, the disordered expression of PRDXs was correlated with prognosis of HCC patients analyzing by online tools, suggesting that PRDXs could be new molecular targets for HCC treatment and prognosis prediction.

scholarly journals CBX3 Is a Prognostic Biomarker That Is Correlated With Lymphocyte Infiltration in Hepatocellular Carcinoma

2021 ◽  
Author(s):  
Jia-Ning Zhang ◽  
Qi fei TAO ◽  
Dong yang Ding ◽  
YUAN YANG ◽  
Wei-Ping Zhou
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cancer ◽  
Immune Cells ◽  
Immune Checkpoint ◽  
Bioinformatics Analysis ◽  
Immune Cell ◽  
Kaplan Meier ◽  
Human Protein Atlas ◽  
Infiltrating Lymphocytes ◽  
Kaplan Meier Plotter

Abstract Background: CBX3 is a key gene that is involved in immune cell regulation, however, its prognostic values and its correlation with infiltrating lymphocytes in various cancers have not been clearly established. This study aims to investigate the role CBX3 in hepatocellular carcinoma (HCC).Methods: We first reviewed the expression of CBX3 in different cancers and adjacent tissues using oncomine database. Next, the authors focus on the expression of CBX3 in hepatocellular carcinoma. Therefore, the expression of CBX3 in hepatocellular carcinoma were analyzed through UALCAN online analysis website and the Human Protein Atlas (www.proteinatlas.org) website. In addition, we further found that CBX3 can be identified as an effective marker for the prognostic guidance of hepatocellular carcinoma according to the Kaplan-Meier plotter database and the Bioinformatics analysis online websites (www.aclbi.com). Next, we used the Bioinformatics analysis online websites to explore whether the expression level of CBX3 in liver cancer is related to the infiltration of certain immune cells. In addition, we also predicted the correlation between immune checkpoint and CBX3 in liver cancer.Results: The analysis results preliminarily show that CBX3 be expressed abnormally in many cancers, and CBX3 was significantly up-regulated in HCC. The high expression of CBX3 indicated survival outcomes and it showed a huge potential as a effective marker for the prognostic guidance of hepatocellular carcinoma. Furthermore, we found that CBX3 in liver cancer is related to the infiltration of certain immune cells, including CD4+ T cells, macrophages and B cells. In addition, the results showed HAVCR2 is most likely to become an effective immune checkpoint for HCC patients immunotherapy with high CBX3 expression.Conclusions: CBX3 is a potential diagnostic and prognostic marker in HCC and related to the infiltration of certain immune cells. It is expected to become a breakthrough point in immunotherapy in the future.

scholarly journals Comprehensive Analysis of Aldehyde Dehydrogenases (ALDHs) and Its Significant Role in Hepatocellular Carcinoma

2021 ◽  
Author(s):  
Senbang Yao ◽  
Wenjun Chen ◽  
He Zuo ◽  
Ziran Bi ◽  
Xiuqing Zhang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cancer ◽  
Oxidative Dna Damage ◽  
Tumor Grade ◽  
The Cancer Genome Atlas ◽  
Kaplan Meier ◽  
Human Protein Atlas ◽  
Cancer Genome Atlas ◽  
The Relationship ◽  
Kaplan Meier Plotter

AbstractOxidative DNA damage is closely related to the occurrence and progression of cancer. Oxidative stress plays an important role in alcohol-induced hepatocellular carcinoma (HCC). Aldehyde dehydrogenase (ALDH) is a family of enzymes that plays an essential role in the reducing oxidative damage. However, how ALDHs family affects alcohol-related HCC remains obscure. We aimed to explore the correlation between the differential expression of ALDHs in patients with HCC and pathological features, as well as the relationship between ALDHs and prognosis, and finally analyze the possible mechanism of ALDHs in targeted therapy of HCC. The data of HCC were downloaded from The Cancer Genome Atlas (TCGA) database. This research explored the expression and prognostic values of ALDHs in HCC using Oncomine, UALCAN, Human Protein Atlas, cBioPortal, Kaplan–Meier plotter, GeneMANIA, Tumor Immune Estimation Resource, GEPIA databases, and WebGestalt. Low mRNA and protein expressions of ALDHs were found to be significantly associated with tumor grade and clinical cancer stages in HCC patients. In particular, the loss of ALDH expression is more obvious in Asians, and its effect on prognosis is far more significant than that in the White race. Our findings play an important role in the study of prognostic markers and anti-liver cancer therapeutic targets for the members of the ALDHs family, especially in patients with liver cancer in Asia.

scholarly journals Long non-coding RNA TUG1 promotes cell progression in hepatocellular carcinoma via regulating miR-216b-5p/DLX2 axis

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Qun Dai ◽  
Jingyi Deng ◽  
Jinrong Zhou ◽  
Zhuhong Wang ◽  
Xiao-feng Yuan ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cancer Progression ◽  
Noncoding Rna ◽  
Critical Role ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Marked Rise ◽  
Hcc Cells

Abstract Background Accumulating evidence indicates that the long noncoding RNA taurine upregulated gene 1(TUG1) plays a critical role in cancer progression and metastasis. However, the overall biological role and clinical significance of TUG1 in hepatocellular carcinoma (HCC) remain largely unknown. Methods The expressions of TUG1, microRNA-216b-5p and distal-less homeobox 2 (DLX2) were detected by Quantitative real-time polymerase chain reaction (qRT-PCR). The target relationships were predicted by StarBase v.2.0 or TargetScan and confirmed by dual-luciferase reporter assay. The cell growth, apoptosis, migration and invasion were detected by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), Flow cytometry and Transwell assays, respectively. All protein expression levels were detected by western blot. Tumor xenografts were implemented to explore the role of TUG1 in vivo. Results We found that there was a marked rise in TUG1 expression in HCC tissues and cells, and knockdown of TUG1 repressed the growth and metastasis and promoted apoptosis of HCC cells. In particular, TUG1 could act as a ceRNA, effectively becoming a sink for miR-216b-5p to fortify the expression of DLX2. Additionally, repression of TUG1 impared the progression of HCC cells by inhibiting DLX2 expression via sponging miR-216b-5p in vitro. More importantly, TUG1 knockdown inhibited HCC tumor growth in vivo through upregulating miR-216b-5p via inactivation of the DLX2. Conclusion TUG1 interacting with miR-216b-5p contributed to proliferation, metastasis, tumorigenesis and retarded apoptosis by activation of DLX2 in HCC.

scholarly journals High Squalene Epoxidase in Tumors Predicts Worse Survival in Patients With Hepatocellular Carcinoma: Integrated Bioinformatic Analysis on NAFLD and HCC

2020 ◽  
Vol 27 (1) ◽  
pp. 107327482091466
Author(s):  
Tingting Shen ◽  
Yunfei Lu ◽  
Qin Zhang
Keyword(s):  
Hepatocellular Carcinoma ◽  
Messenger Rna ◽  
Disease Free Survival ◽  
Bioinformatic Analysis ◽  
Gene Expression Omnibus ◽  
The Cancer Genome Atlas ◽  
Squalene Epoxidase ◽  
Nonalcoholic Fatty Liver ◽  
Kaplan Meier ◽  
High Level

This study aimed to identify candidate biomarkers for predicting outcomes in nonalcoholic fatty liver disease (NAFLD) and hepatocellular carcinoma (HCC). Using Gene Expression Omnibus and The Cancer Genome Atlas (TCGA) databases, we identified common upregulated differential expressed genes (DEGs) in patients with NAFLD/nonalcoholic steatohepatitis (NASH) and HCC and conducted survival analysis of these upregulated DEGs with HCC outcomes. Two common upregulated DEGs including squalene epoxidase (SQLE) and EPPK1 messenger RNA (mRNA) were significantly upregulated in NAFLD, NASH, and HCC tissues, both in GSE45436 ( P < .001) and TCGA profile ( P < .001). Both SQLE and EPPK1 mRNA were upregulated in 15.56% and 8.06% patients with HCC in TCGA profile. Overexpression of SQLE in tumors was significantly associated with worse overall survival (OS) and disease-free survival (DFS) in patients with HCC (log-rank P = .027 and log-rank P = .048, respectively), while no statistical significances of OS and DFS were found in EPPK1 groups (both log-rank P > .05). For validation, SQLE upregulation contributed to significantly worse OS in patients wih HCC using Kaplan-Meier plotter analysis (hazard ratio = 1.43, 95% confidence interval: 1.01-2.02, log-rank P = .043). In addition, high level of SQLE significantly associated with advanced neoplasm histologic grade, advanced AJCC stage, and α-fetoprotein elevation ( P = .036, .045, and .029, respectively). Squalene epoxidase is associated with OS and DFS and serves as a novel prognostic biomarker for patients with HCC.

scholarly journals Long noncoding RNA CASC2c inhibited cell proliferation in hepatocellular carcinoma by inactivated ERK1/2 and Wnt/β-catenin signaling pathway

2019 ◽  
Vol 22 (3) ◽  
pp. 302-310 ◽  
Author(s):  
Q. Y. Li ◽  
K. Yang ◽  
F. G. Liu ◽  
X. G. Sun ◽  
L. Chen ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cancer Progression ◽  
Noncoding Rna ◽  
Molecular Mechanisms ◽  
Cancer Susceptibility ◽  
Vital Role ◽  
Migration And Invasion ◽  
Tumor Tissues ◽  
Hcc Cells

Abstract Purpose Long non-coding RNAs (lncRNAs) have been shown to play important roles in tumorigenesis, but their biological functions and the underlying molecular mechanisms remain unclear. Alternative splicing of five exons results in three transcript variants of cancer susceptibility 2 (CASC2): the lncRNAs CASC2a, CASC2b, and CASC2c. CASC2a/b have been found to have crucial regulatory functions in a number of malignancies, but few studies have examined the effects of CASC2c in cancers. The objective of the study was to investigate the role of CASC2c in the proliferation and apoptosis of hepatocellular carcinoma (HCC) cells. Methods This study first investigated the expression levels of CASC2c in tumor tissues, corresponding non-tumor tissues and cells using quantitative real-time polymerase chain reaction. The function and underlying molecular mechanism of CASC2c in human HCC were investigated in QGY-7703 cell line, as well as in gastric cancer (GC) cell and colorectal cancer (CRC) cell. Results In the present work, we observed that CASC2c was significantly down-regulated in HCC tissues and cells. Moreover, its overexpression remarkably inhibited the growth, migration, and invasion of HCC cells in vitro and promoted their apoptosis. Furthermore, we demonstrated that CASC2c overexpression decreased p-ERK1/2 levels in HCC, GC, and CRC cells. Interestingly, while overexpression of CASC2c decreased β-catenin expression in HCC and GC cells, it increased that in CRC cells. Conclusion The lncRNA–CASC2c has a vital role in tumorigenesis and cancer progression, and may serve as a biomarker or therapeutic target in cancer treatment via down-regulation of the ERK1/2 and Wnt/β-catenin signaling pathways.

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