Effect of an lncRNA-associated ceRNA regulatory network in MVI-positive hepatocellular carcinoma on their sensitivity to sorafenib.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16615-e16615
Author(s):  
Zhiwen Luo ◽  
Xinyu Bi
Keyword(s):  
Hepatocellular Carcinoma ◽  
Expression Profiles ◽  
Recurrence Risk ◽  
Vital Role ◽  
Prognostic Biomarkers ◽  
Protein Coding ◽  
Functional Roles ◽  
Cerna Network ◽  
Mirna Sponges ◽  
Regulate Protein

e16615 Background: Microvascular invasion (MVI) is a histological feature of hepatocellular carcinoma (HCC) related to aggressiveness. But different sensitivity to first line targeted drug, sorafenib, in MVI+ HCC has been observed. Long noncoding RNAs (lncRNAs) can act as microRNA (miRNA) sponges to regulate protein-coding gene expression; so lncRNAs are considered as a major part of competitive endogenous RNA (ceRNA) network and have attracted growing attention. We explored the regulatory mechanisms and functional roles of lncRNAs as ceRNAs in MVI+ HCC, and ceRNA network’s potential impact on prognosis and sensitivity to sorafenib in MVI+ HCC patient. Methods: We studied the expression profiles, prognostic value of lncRNA, miRNA, and mRNA from MVI+ HCC patients, established a prognosis-related network of dysregulated ceRNAs and analyzed its role in sensitivity to sorafenib and radiomics features by bioinformatics methods. Results: A ceRNA network including 13 lncRNAs, 3 miRNAs, and 2 mRNAs specific to MVI+ HCC was established. 6 lncRNAs ( ARHGEF7-AS1, ATP2B2-IT1, LINC00330, MUC2, TLR8-AS1 and ZNF385D-AS1), 2 miRNAs ( hsa-mir-206 and hsa-mir-373) and two mRNAs ( PAX3, SIK1) were prognostic biomarkers for MVI+ HCC. PAX3 was an unfavorable prognostic gene (HR = 1.9, 95%CI 1.01 ~ 3.60), while SIK1 favored the prognosis (HR = 0.4, 95%CI 0.19 ~ 0.85). PAX3 as a stratification in recurrence predicting model was used to identify MVI+ HCC with high or low recurrence risk. Datamining into the dataset of phase 3 STORM trial showed no difference in the influence of PAX3 level on the outcome between sorafenib HCC group and placebo HCC group. However, deep datamining into GDSC dataset revealed our high PAX3 group in MVI+ HCC related to resistance to sorafenib ( P = 0.0039). Radiomics features were extracted from CT of MVI+ HCC, and texture analysis in MVI+ HCCs is ongoing. Conclusions: The proposed ceRNA network may help elucidate the regulatory mechanism by which lncRNAs function as ceRNAs and contribute to the pathogenesis of MVI in HCC. Importantly, the candidate lncRNAs, miRNAs, and mRNAs involved in the ceRNA network have shown to be potential therapeutic targets and prognostic biomarkers for MVI+ HCC. PAX3 might play a vital role in the mechanism of sorafenib resistance in MVI+ HCC, exclusively, this aggressive HCC subtype. The ongoing experiments on radiomics might add potent supports to identify sorafenib sensitive MVI+ HCC.

scholarly journals Characterization and Analysis of Whole Transcriptome of Giant Panda Spleens: Implying Critical Roles of Long Non-Coding RNAs in Immunity

2018 ◽  
Vol 46 (3) ◽  
pp. 1065-1077 ◽  
Author(s):  
Rui Peng ◽  
Yuliang Liu ◽  
Zhigang Cai ◽  
Fujun Shen ◽  
Jiasong Chen ◽  
...  
Keyword(s):  
Giant Panda ◽  
Pathological Condition ◽  
Species Conservation ◽  
Large Set ◽  
Illumina Hiseq ◽  
Protein Coding ◽  
Giant Pandas ◽  
Functional Roles ◽  
Non Coding Rnas ◽  
Mirna Sponges

Background/Aims: Giant pandas, an endangered species, are a powerful symbol of species conservation. Giant pandas may suffer from a variety of diseases. Owing to their highly specialized diet of bamboo, giant pandas are thought to have a relatively weak ability to resist diseases. The spleen is the largest organ in the lymphatic system. However, there is little known about giant panda spleen at a molecular level. Thus, clarifying the regulatory mechanisms of spleen could help us further understand the immune system of the giant panda as well as its conservation. Methods: The two giant panda spleens were from two male individuals, one newborn and one an adult, in a non-pathological condition. The whole transcriptomes of mRNA, lncRNA, miRNA, and circRNA in the two spleens were sequenced using the Illumina HiSeq platform. EBseq and IDEG6 were used to observe the differentially expressed genes (DEGs) between these two spleens. Gene Ontology and KEGG analyses were used to annotate the function of DEGs. Furthermore, networks between non-coding RNAs and protein-coding genes were constructed to investigate the relationship between non-coding RNAs and immune-associated genes. Results: By comparative analysis of the whole transcriptomes of these two spleens, we found that one of the major roles of lncRNAs could be involved in the regulation of immune responses of giant panda spleens. In addition, our results also revealed that microRNAs and circRNAs may have evolved to regulate a large set of biological processes of giant panda spleens, and circRNAs may function as miRNA sponges. Conclusion: To our knowledge, this is the first report of lncRNAs and circRNAs in giant panda, which could be a useful resource for further giant panda research. Our study reveals the potential functional roles of miRNAs, lncRNAs, and circRNAs in giant panda spleen.

scholarly journals circEPS15 Overexpression in Hepatocellular Carcinoma Modulates Tumor Invasion and Migration

2020 ◽  
Author(s):  
Maolin Tian ◽  
Gang Li ◽  
Bin Jiang ◽  
Sadula Abuduhaibaier ◽  
Dianrong Xiu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Cycle ◽  
Tumor Invasion ◽  
Expression Profiles ◽  
The Cancer Genome Atlas ◽  
Circular Rnas ◽  
Invasion And Migration ◽  
Qrt Pcr ◽  
Cerna Network ◽  
And Migration

Abstract Background: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths worldwide. Recent evidence indicates that circular RNAs (circRNAs) play important roles in tissue development, gene regulation, and carcinogenesis. However, whether circRNAs are involved in HCC progression and encode functional proteins remains largely unknown.Methods: Circular RNA microarrays were performed using three pathologically diagnosed HCC samples and their paired adjacent normal liver tissues. Cell invasion, migration, cell cycle, and apoptosis after circRNA overexpression were measured using a transwell culture system, a wound healing assay, and flow cytometry . Full-length, mutated, and truncated sequences of circEPS15 with a FLAG tag were inserted inside a circular expression vector. Western blotting was used to confirm circEPS15 expression and the requirement of internal ribosomal entry site (IRES) elements within the circRNA. The miRNA and mRNA expression profiles were obtained by analyzing data retrieved from The Cancer Genome Atlas (TCGA) database. We then constructed a ceRNA network of mRNAs, miRNAs, and circEPS15. Using tissue samples from own patients, we also verified certain analytical results with quantitative real-time PCR (qRT-PCR).Results: The expression of circEPS15 was downregulated in HCC tissues, and the survival curves showed that low circEPS15 levels were associated with poor overall survival in HCC patients. Overexpression of circEPS15 suppressed tumor invasion and migration by inhibiting the TJP1/CDH2/VIM signaling pathway and retarded cell cycle progression, but it had no effect on cell apoptosis. ceRNA analysis and qRT-PCR showed that there might be a circRNA (circEPS15)-miRNA (miR-24-3p)-mRNA (CIDEA) network in HCC. The spanning junction open reading frame in circEPS15 driven by IRES encoded a novel protein.Conclusions: Endogenous circEPS15 plays a novel role in repressing HCC through the ceRNA network and encoding a functional protein.

scholarly journals Characterisation and functional predictions of canine long non-coding RNAs

2018 ◽  
Author(s):  
Céline Le Béguec ◽  
Valentin Wucher ◽  
Lætitia Lagoutte ◽  
Edouard Cadieu ◽  
Nadine Botherel ◽  
...  
Keyword(s):  
Expression Profiles ◽  
Expression Patterns ◽  
Regulatory Elements ◽  
Domestic Dog ◽  
Tissue Type ◽  
Protein Coding ◽  
Functional Roles ◽  
Integrative Study ◽  
Non Coding Rnas ◽  
Biological Functionality

AbstractLong non-coding RNAs (lncRNAs) are a family of heterogeneous RNAs that play major roles in multiple biological processes. We recently identified an extended repertoire of more than 10,000 lncRNAs of the domestic dog however, predicting their biological functionality remains challenging. In this study, we have characterised the expression profiles of 10,444 canine lncRNAs in 26 distinct tissue types, representing various anatomical systems. We showed that lncRNA expressions are mainly clustered by tissue type and we highlighted that 44% of canine lncRNAs are expressed in a tissue-specific manner. We further demonstrated that tissue-specificity correlates with specific families of canine transposable elements. In addition, we identified more than 900 conserved dog-human lncRNAs for which we show their overall reproducible expression patterns between dog and humans through comparative transcriptomics. Finally, co-expression analyses of lncRNA and neighbouring protein-coding genes identified more than 3,400 canine lncRNAs, suggesting that functional roles of these lncRNAs act as regulatory elements. Altogether, this genomic and transcriptomic integrative study of lncRNAs constitutes a major resource to investigate genotype to phenotype relationships and biomedical research in the dog species.

Potential Diagnostic and Therapeutic Targets for Hepatocellular Carcinoma Based on Exosome-Derived Competitive Endogenous RNA Network

2021 ◽  
Author(s):  
Yuan Tian ◽  
Dongliang Yang ◽  
Tieshan Wang ◽  
He Bu ◽  
JinBao Wu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Target Genes ◽  
Immune Escape ◽  
Malignant Tumors ◽  
Expression Profiles ◽  
Therapeutic Targets ◽  
Differentially Expressed ◽  
Cerna Network ◽  
Differentially Expressed Mirnas ◽  
Competitive Endogenous Rna

Abstract Background: Hepatocellular carcinoma (HCC) is one of the most malignant tumors in the world. The pathogenesis of HCC is complex and closely related to chronic uncontrollable inflammation. As a bridge between inflammation and cancer, circulating exosomes play a vital role in early tumorigenesis, metastasis, and immune escape. Studies have shown that exosomes containing specific RNAs may be potential diagnostic and therapeutic targets for HCC. Purpose The current research investigated key circRNA through exosome-derived competitive endogenous RNA network based on the ExoRBase database. Methods: The circRNA, lncRNA, and mRNA expression profiles of human blood samples were downloaded from the ExoRBase database. At the standard of P<0.05 and log FC>0, differentially expressed genes (DEGs) were further identified between normal human and HCC patients. The co-expressed pairs of DEGs were predicted by TargetScan, miRcode, and StarBase databases. The ceRNA network was constructed by Cytoscape software. Subsequently, target genes corresponding to circRNA in the ceRNA network were annotated and analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Gene and Genome (KEGG). The potential transcription factors were screened by FunRich database. Results: At the criterion of P<0.05 and log FC>0, 13 differentially expressed circRNAs(DECs) were identified with 9 up-regulated and 4 down-regulated. The co-expressed differentially expressed miRNAs-mRNAs (DEMis-DEMs) (620 pairs), differentially expressed miRNAs- LncRNAs (DEMis-DElncRNA) (684 pairs) and DEMis-DECs (53 pairs) were finally predicted to construct the ceRNA network. The GO analysis indicated that target genes in the ceRNA network were mainly enriched in the molecular function of protein serine/threonine kinase activity. KEGG pathway analysis suggested target genes were enriched in two pathways of MAPK and central carbon metabolism. Conclusion: The study provides a valuable reference for HCC through the ceRNA network in exosomes. Besides, hsa_circ_0000284 may be potential diagnostic markers of HCC.

scholarly journals Construction and Comparison of ceRNA Regulatory Network for Different Age Female Breast Cancer

2021 ◽  
Vol 12 ◽  
Author(s):  
Zhi-Qin Liu ◽  
Gao-Tao Zhang ◽  
Li Jiang ◽  
Chun-Qing Li ◽  
Que-Ting Chen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Survival Analysis ◽  
Regulatory Networks ◽  
Expression Profiles ◽  
Female Breast Cancer ◽  
Prognostic Biomarkers ◽  
Receptor Interaction ◽  
Elderly Age ◽  
Cerna Network ◽  
Female Breast

Studies have shown the difference appearing among the prognosis of patients in different age groups. However, the molecular mechanism implicated in this disparity have not been elaborated. In this study, expression profiles of female breast cancer (BRCA) associated mRNAs, lncRNAs and miRNAs were downloaded from the TCGA database. The sample were manually classified into three groups according to their age at initial pathological diagnosis: young (age ≤ 39 years), elderly (age ≥ 65 years), and intermediate (age 40–64 years). lncRNA-miRNA-mRNA competitive endogenous RNA (ceRNA) network was respectively constructed for different age BRCA. Then, the biological functions of differentially expressed mRNAs (DEmRNAs) in ceRNA network were further investigated by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Finally, survival analysis was used to identify prognostic biomarkers for different age BRCA patients. We identified 13 RNAs, 38 RNAs and 40 RNAs specific to patients aged ≤ 39 years, aged 40–64 years, and aged ≥ 65 years, respectively. Furthermore, the unique pathways were mainly enriched in cytokine-cytokine receptor interaction in patients aged 40–64 years, and were mainly enriched in TGF-beta signaling pathway in patients aged ≥ 65 years. According to the survival analysis, AGAP11, has-mir-301b, and OSR1 were respectively functioned as prognostic biomarkers in young, intermediate, and elderly group. In summary, our study identified the differences in the ceRNA regulatory networks and provides an effective bioinformatics basis for further understanding of the pathogenesis and predicting outcomes for different age BRCA.

scholarly journals Comprehensive Analysis of Competing Endogenous RNA Network Focusing on Long Noncoding RNA Involved in Cirrhotic Hepatocellular Carcinoma

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Yuli Zhang ◽  
Dinggui Chen ◽  
Miaomiao Yang ◽  
Xianfeng Qian ◽  
Chunmei Long ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Survival Analysis ◽  
Noncoding Rna ◽  
Expression Profiles ◽  
The Cancer Genome Atlas ◽  
Prognostic Indicators ◽  
Competing Endogenous Rna ◽  
Regulatory Pathways ◽  
Qrt Pcr ◽  
Cerna Network

The role of long noncoding RNAs- (lncRNAs-) associated competing endogenous RNA (ceRNA) in the field of hepatocellular carcinoma (HCC) biology is well established, but the involvement of lncRNAs competing interactions in the progression of liver cirrhosis to HCC is still unclear. We aimed to explore the differential expression profiles of lncRNAs, microRNAs (miRNA), and messenger RNAs (mRNAs) to construct a functional ceRNA network in cirrhotic HCC. The lncRNA, miRNA, and mRNA expression datasets were obtained from Gene Expression Omnibus and The Cancer Genome Atlas. Based on miRanda and TargetScan, the HCC-specific ceRNA network was constructed to illustrate the coexpression regulatory relationship of lncRNAs, miRNAs, and mRNAs. The potential prognostic indicators in the network were confirmed by survival analysis and validated by qRT-PCR. A total of 74 lncRNAs, 36 intersection miRNAs, and 949 mRNAs were differentially expressed in cirrhotic HCC samples compared with cirrhosis samples. We constructed a ceRNA network, including 47 lncRNAs, 35 miRNAs, and 168 mRNAs. Survival analysis demonstrated that 2 lncRNAs (EGOT and SERHL), 4 miRNAs, and 40 mRNAs were significantly associated with the overall survival of HCC patients. Two novel regulatory pathways, EGOT-miR-32-5p-XYLT2 axis and SERHL-miR-1269a/miR-193b-3p-BCL2L1/SYK/ARNT/CHST3/LPCAT1 axis, were built up and contribute to the underlying mechanism of HCC pathogenesis. The higher-expressed SERHL was associated with a higher risk of all-cause death. The expressions of SERHL-miR-1269a-BCL2L1 were significantly different using qRT-PCR in vitro studies. lncRNAs EGOT and SERHL might serve as effective prognostic biomarkers and potential therapeutic targets in cirrhotic HCC treatment.

scholarly journals Identification of Prognostic Biomarkers and Correlation With Immune Infiltrates in Hepatocellular Carcinoma Based on a Competing Endogenous RNA Network

2021 ◽  
Vol 12 ◽  
Author(s):  
Zhangya Pu ◽  
Yuanyuan Zhu ◽  
Xiaofang Wang ◽  
Yun Zhong ◽  
Fang Peng ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
T Cells ◽  
Survival Analysis ◽  
Immune Cell ◽  
Cox Regression ◽  
Quantitative Polymerase Chain Reaction ◽  
Prognostic Biomarkers ◽  
Hub Genes ◽  
Immune Infiltration ◽  
Cerna Network

BackgroundHepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide. Recently, competing endogenous RNAs (ceRNA) have revealed a significant role in the progression of HCC. Herein, we aimed to construct a ceRNA network to identify potential biomarkers and illustrate its correlation with immune infiltration in HCC.MethodsRNA sequencing data and clinical traits of HCC patients were downloaded from TCGA. The limma R package was used to identify differentially expressed (DE) RNAs. The predicted prognostic model was established using univariate and multivariate Cox regression. A K-M curve, TISIDB and GEPIA website were utilized for survival analysis. Functional annotation was determined using Enrichr and Reactome. Protein-to-protein network analysis was implemented using SRTNG and Cytoscape. Hub gene expression was validated by quantitative polymerase chain reaction, Oncomine and the Hunan Protein Atlas database. Immune infiltration was analyzed by TIMMER, and Drugbank was exploited to identify bioactive compounds.ResultsThe predicted model that was established revealed significant efficacy with 3- and 5-years of the area under ROC at 0.804 and 0.744, respectively. Eleven DEmiRNAs were screened out by a K-M survival analysis. Then, we constructed a ceRNA network, including 56 DElncRNAs, 6 DEmiRNAs, and 28 DEmRNAs. The 28 DEmRNAs were enriched in cancer-related pathways, for example, the TNF signaling pathway. Moreover, six hub genes, CEP55, DEPDC1, KIF23, CLSPN, MYBL2, and RACGAP1, were all overexpressed in HCC tissues and independently correlated with survival rate. Furthermore, expression of hub genes was related to immune cell infiltration in HCC, including B cells, CD8+ T cells, CD4+ T cells, monocytes, macrophages, neutrophils, and dendritic cells.ConclusionThe findings from this study demonstrate that CEP55, DEPDC1, KIF23, CLSPN, MYBL2, and RACGAP1 are closely associated with prognosis and immune infiltration, representing potential therapeutic targets or prognostic biomarkers in HCC.

scholarly journals Inferring Cell Subtypes and LncRNA Function by a Cell-Specific CeRNA Network in Breast Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Xin Chen ◽  
Jing Xu ◽  
Feng Zeng ◽  
Chao Yang ◽  
Weijun Sun ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Single Cell ◽  
Expression Profiles ◽  
Topological Analysis ◽  
Early Response ◽  
Protein Coding ◽  
Cerna Network ◽  
Estrogen Response ◽  
A Cell ◽  
Novel Strategy

Single-cell RNA sequencing is a powerful tool to explore the heterogeneity of breast cancer. The identification of the cell subtype that responds to estrogen has profound significance in breast cancer research and treatment. The transcriptional regulation of estrogen is an intricate network involving crosstalk between protein-coding and non-coding RNAs, which is still largely unknown, particularly at the single cell level. Therefore, we proposed a novel strategy to specify cell subtypes based on a cell-specific ceRNA network (CCN). The CCN was constructed by integrating a cell-specific RNA-RNA co-expression network (RCN) with an existing ceRNA network. The cell-specific RCN was built based on single cell expression profiles with predefined reference cells. Heterogeneous cell subtypes were inferred by enriching RNAs in CCN to the estrogen response hallmark. Edge biomarkers were identified in the early estrogen response subtype. Topological analysis revealed that NEAT1 was a hub lncRNA for the early response subtype, and its ceRNAs could predict patient survival. Another hub lncRNA, DLEU2, could potentially be involved in GPCR signaling, based on CCN. The CCN method that we proposed here facilitates the inference of cell subtypes from a network perspective and explores the function of hub lncRNAs, which are promising targets for RNA-based therapeutics.

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.

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