scholarly journals CircRNAs as Potential Blood Biomarkers and Key Elements in Regulatory Networks in Gastric Cancer

2022 ◽  
Vol 23 (2) ◽  
pp. 650
Author(s):  
Laís Reis-das-Mercês ◽  
Tatiana Vinasco-Sandoval ◽  
Rafael Pompeu ◽  
Aline Cruz Ramos ◽  
Ana K. M. Anaissi ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Minimally Invasive ◽  
Regulatory Networks ◽  
Expression Profiles ◽  
Functional Enrichment ◽  
Circular Rnas ◽  
Rna Seq ◽  
Tissue Samples ◽  
Molecular Alterations ◽  
Non Coding Rnas

Gastric cancer (GC) is the fifth most common type of cancer and the third leading cause of cancer death in the world. It is a disease that encompasses a variety of molecular alterations, including in non-coding RNAs such as circular RNAs (circRNAs). In the present study, we investigated hsa_circ_0000211, hsa_circ_0000284, hsa_circ_0000524, hsa_circ_0001136 and hsa_circ_0004771 expression profiles using RT-qPCR in 71 gastric tissue samples from GC patients (tumor and tumor-adjacent samples) and volunteers without cancer. In order to investigate the suitability of circRNAs as minimally invasive biomarkers, we also evaluated their expression profile through RT-qPCR in peripheral blood samples from patients with and without GC (n = 41). We also investigated the predicted interactions between circRNA-miRNA-mRNA and circRNA-RBP using the KEGG and Reactome databases. Overall, our results showed that hsa_circ_0000211, hsa_circ_0000284 and hsa_circ_0004771 presented equivalent expression profiles when analyzed by different methods (RNA-Seq and RT-qPCR) and different types of samples (tissue and blood). Further, functional enrichment results identified important signaling pathways related to GC. Thus, our data support the consideration of circRNAs as new, minimally invasive biomarkers capable of aiding in the diagnosis of GC and with great potential to be applied in clinical practice.

scholarly journals A Novel LncRNA-miRNA-mRNA Triple Network Identifies LncRNA RP11-363E7.4 as An Important Regulator of miRNA and Gene Expression in Gastric Cancer

2018 ◽  
Vol 47 (3) ◽  
pp. 1025-1041 ◽  
Author(s):  
Pengcheng Wang ◽  
Jing Li ◽  
Wei Zhao ◽  
Chunyang Shang ◽  
Xian Jiang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gastric Cancer ◽  
Regulatory Networks ◽  
Functional Enrichment ◽  
Microrna Target ◽  
Kaplan Meier ◽  
Important Regulator ◽  
Non Coding Rnas ◽  
Gc Gene ◽  
Insight Into

Background/Aims: Recent evidence has shown that some long non-coding RNAs (lncRNAs) play important roles in various biological processes. However, the regulatory mechanism of lncRNA in gastric cancer (GC) remains unclear. Methods: We reannotated the GC gene expression profile into a lncRNA-mRNA biphasic profile and integrated the microRNA target data to construct a global GC triple network. A further clustering and random walk with restart analyses was performed on the triple network from the level of topology analyses. Quantitative real-time PCR was used to determine expression of lncRNA RP11-363E7.4. Kaplan-Meier analyses was performed to evaluate the prognostic value of lncRNA RP11-363E7.4. Results: We constructed a gastric cancer lncRNA-miRNA-mRNA network (GCLMN) including six lncRNAs, 332 mRNAs, and 3,707 edges. For the shared lncRNA RP11-363E7.4, the interacting gene and microRNA functional enrichment studies implied that lncRNA RP11-363E7.4 might function as a new regulator in GC. The expression of lncRNA RP11-363E7.4 was downregulated compared with that of paracarcinoma tissues in five GC samples. High expression of lncRNA RP11-363E7.4 was found to be correlated to better overall survival (OS) for GC patients. Conclusions: This study focused on GC lncRNA-miRNA-mRNA regulatory networks, and found that lncRNA RP11-363E7.4 was a new GC risk lncRNA, which might provide novel insight into a better understanding of the pathogenesis of GC.

scholarly journals Analyses of circRNA and mRNA Profiles in Vogt–Koyanagi–Harada Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Jia Shu ◽  
Guannan Su ◽  
Jun Zhang ◽  
Zhangluxi Liu ◽  
Rui Chang ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Signaling Pathway ◽  
Expression Profiles ◽  
Adaptive Immune Response ◽  
Cell Receptor ◽  
Functional Enrichment ◽  
Circular Rnas ◽  
Marker Genes ◽  
Rna Seq ◽  
Vkh Disease

Recent studies revealed that circular RNAs (circRNAs) are important in numerous biological process and involved in autoimmune diseases. However, their role in Vogt–Koyanagi–Harada (VKH) disease, a classical autoimmune disease, is not yet known. This research aimed to study the expression profile of mRNAs, microRNAs (miRNAs) and circRNAs and investigate the influence of circRNAs on the pathogenesis of VKH disease. We identified circRNAs, miRNAs, and mRNAs expression profiles in CD4+ T cells between 4 VKH patients and 3 healthy controls using the whole-transcriptome sequencing (RNA-seq) technique. We discovered that a total of 5088 mRNAs, 451 circRNAs and 433 miRNAs were differently expressed. The GO and KEGG pathway enrichment analyses were performed for significantly differentially expressed circRNAs and mRNAs. GSEA was conducted for all mRNAs. The functional enrichment suggested that the inflammatory response, the adaptive immune response, NF-kappa B signaling pathway, Th17 cell differentiation, Th1 and Th2 cell differentiation and T cell receptor signaling pathway were associated with VKH disease. In addition, based on the immune-related genes we screened, the circRNA-miRNA-mRNA ceRNA network was analyzed and constructed. Ten differently expressed mRNAs (LAT, ZAP70, ITK, ICOS, RASGRP1, PAG1, PLCG1, PRKCQ, LCK, CARD11) and 5 differently expressed circRNAs (hsa_circ_0033144, hsa_circ_0000233, hsa_circ_0000396, hsa_circ_0001924, hsa_circ_0001320) were selected to be validated by Real-time qPCR (RT-qPCR). The results of RT-qPCR turned out to be consistent with RNA-seq data. Further analysis showed that hsa_circ_0001320 and hsa_circ_0001924 may serve as crucial candidate marker genes of VKH disease. These results reveal that circRNAs may have a crucial immunomodulatory function in the pathophysiological process of VKH disease.

Radio-Susceptibility of Nasopharyngeal Carcinoma: Focus on Epstein- Barr Virus, MicroRNAs, Long Non-Coding RNAs and Circular RNAs

2020 ◽  
Vol 13 (3) ◽  
pp. 192-205 ◽  
Author(s):  
Fanghong Lei ◽  
Tongda Lei ◽  
Yun Huang ◽  
Mingxiu Yang ◽  
Mingchu Liao ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Regulatory Networks ◽  
Epstein Barr Virus ◽  
Molecular Mechanisms ◽  
Acquired Resistance ◽  
Treatment Strategies ◽  
Circular Rnas ◽  
Barr Virus ◽  
Non Coding Rnas ◽  
Epstein Barr

Nasopharyngeal carcinoma (NPC) is a type of head and neck cancer. As a neoplastic disorder, NPC is a highly malignant squamous cell carcinoma that is derived from the nasopharyngeal epithelium. NPC is radiosensitive; radiotherapy or radiotherapy combining with chemotherapy are the main treatment strategies. However, both modalities are usually accompanied by complications and acquired resistance to radiotherapy is a significant impediment to effective NPC therapy. Therefore, there is an urgent need to discover effective radio-sensitization and radio-resistance biomarkers for NPC. Recent studies have shown that Epstein-Barr virus (EBV)-encoded products, microRNAs (miRNAs), long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs), which share several common signaling pathways, can function in radio-related NPC cells or tissues. Understanding these interconnected regulatory networks will reveal the details of NPC radiation sensitivity and resistance. In this review, we discuss and summarize the specific molecular mechanisms of NPC radio-sensitization and radio-resistance, focusing on EBV-encoded products, miRNAs, lncRNAs and circRNAs. This will provide a foundation for the discovery of more accurate, effective and specific markers related to NPC radiotherapy. EBVencoded products, miRNAs, lncRNAs and circRNAs have emerged as crucial molecules mediating the radio-susceptibility of NPC. This understanding will improve the clinical application of markers and inform the development of novel therapeutics for NPC.

scholarly journals Novel Identified Circular Transcript of RCAN2, circ-RCAN2, Shows Deviated Expression Pattern in Pig Reperfused Infarcted Myocardium and Hypoxic Porcine Cardiac Progenitor Cells In Vitro

2021 ◽  
Vol 22 (3) ◽  
pp. 1390
Author(s):  
Julia Mester-Tonczar ◽  
Patrick Einzinger ◽  
Johannes Winkler ◽  
Nina Kastner ◽  
Andreas Spannbauer ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Progenitor Cells ◽  
Regulatory Networks ◽  
Circular Rnas ◽  
Cardiac Progenitor Cells ◽  
Tissue Samples ◽  
Healthy Myocardium ◽  
Acute Mi

Circular RNAs (circRNAs) are crucial in gene regulatory networks and disease development, yet circRNA expression in myocardial infarction (MI) is poorly understood. Here, we harvested myocardium samples from domestic pigs 3 days after closed-chest reperfused MI or sham surgery. Cardiac circRNAs were identified by RNA-sequencing of rRNA-depleted RNA from infarcted and healthy myocardium tissue samples. Bioinformatics analysis was performed using the CIRIfull and KNIFE algorithms, and circRNAs identified with both algorithms were subjected to differential expression (DE) analysis and validation by qPCR. Circ-RCAN2 and circ-C12orf29 expressions were significantly downregulated in infarcted tissue compared to healthy pig heart. Sanger sequencing was performed to identify the backsplice junctions of circular transcripts. Finally, we compared the expressions of circ-C12orf29 and circ-RCAN2 between porcine cardiac progenitor cells (pCPCs) that were incubated in a hypoxia chamber for different time periods versus normoxic pCPCs. Circ-C12orf29 did not show significant DE in vitro, whereas circ-RCAN2 exhibited significant ischemia-time-dependent upregulation in hypoxic pCPCs. Overall, our results revealed novel cardiac circRNAs with DE patterns in pCPCs, and in infarcted and healthy myocardium. Circ-RCAN2 exhibited differential regulation by myocardial infarction in vivo and by hypoxia in vitro. These results will improve our understanding of circRNA regulation during acute MI.

scholarly journals Screening Driving Transcription Factors in the Processing of Gastric Cancer

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Guangzhong Xu ◽  
Kai Li ◽  
Nengwei Zhang ◽  
Bin Zhu ◽  
Guosheng Feng
Keyword(s):  
Gastric Cancer ◽  
Transcription Factors ◽  
Regulatory Network ◽  
Target Genes ◽  
Transcriptional Regulatory Network ◽  
Expression Profiles ◽  
Functional Enrichment ◽  
Regulatory Mechanisms ◽  
Integrated Analysis ◽  
Transcriptional Regulatory

Background. Construction of the transcriptional regulatory network can provide additional clues on the regulatory mechanisms and therapeutic applications in gastric cancer.Methods. Gene expression profiles of gastric cancer were downloaded from GEO database for integrated analysis. All of DEGs were analyzed by GO enrichment and KEGG pathway enrichment. Transcription factors were further identified and then a global transcriptional regulatory network was constructed.Results. By integrated analysis of the six eligible datasets (340 cases and 43 controls), a bunch of 2327 DEGs were identified, including 2100 upregulated and 227 downregulated DEGs. Functional enrichment analysis of DEGs showed that digestion was a significantly enriched GO term for biological process. Moreover, there were two important enriched KEGG pathways: cell cycle and homologous recombination. Furthermore, a total of 70 differentially expressed TFs were identified and the transcriptional regulatory network was constructed, which consisted of 566 TF-target interactions. The top ten TFs regulating most downstream target genes were BRCA1, ARID3A, EHF, SOX10, ZNF263, FOXL1, FEV, GATA3, FOXC1, and FOXD1. Most of them were involved in the carcinogenesis of gastric cancer.Conclusion. The transcriptional regulatory network can help researchers to further clarify the underlying regulatory mechanisms of gastric cancer tumorigenesis.

scholarly journals Identification of Gastric Cancer-Related Circular RNA through Microarray Analysis and Bioinformatics Analysis

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Wei Gu ◽  
Ying Sun ◽  
Xiong Zheng ◽  
Jin Ma ◽  
Xiao-Ying Hu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gastric Cancer ◽  
Microarray Analysis ◽  
Cancer Progression ◽  
Pathway Analysis ◽  
Bioinformatics Analysis ◽  
Malignant Tumors ◽  
Expression Profiles ◽  
Circular Rnas ◽  
Target Mrnas

Gastric cancer is one of the common malignant tumors worldwide. Increasing studies have indicated that circular RNAs (circRNAs) play critical roles in the cancer progression and have shown great potential as useful markers and therapeutic targets. However, the precise mechanism and functions of most circRNAs are still unknown in gastric cancer. In the present study, we performed a microarray analysis to detect circRNA expression changes between tumor samples and adjacent nontumor samples. The miRNA expression profiles were obtained from the National Center of Biotechnology Information Gene Expression Omnibus (GEO). The differentially expressed circRNAs and miRNAs were identified through fold change filtering. The interactions between circRNAs and miRNAs were predicted by Arraystar’s home-made miRNA target prediction software. After circRNA-related miRNAs and dysregulated miRNAs were intersected, 23 miRNAs were selected. The target mRNAs of miRNAs were predicted by TarBase v7.0. Gene ontology (GO) enrichment analysis and pathway analysis were performed using standard enrichment computational methods for the target mRNAs. The results of pathway analysis showed that p53 signaling pathway and hippo signal pathway were significantly enriched and CCND2 was a cross-talk gene associated with them. Finally, a circRNA-miRNA-mRNA regulation network was constructed based on the gene expression profiles and bioinformatics analysis results to identify hub genes and hsa_circRNA_101504 played a central role in the network.

Analysis of Expression Profiles of mRNA and lncRNA in Oviduct During Estrus Phase of Sheep (Ovis Aries) with Two Fecundity (FecB Gene) Genotypes

2021 ◽  
Author(s):  
Weihao Chen ◽  
Zhifeng Li ◽  
Wei Sun ◽  
Mingxing Chu
Keyword(s):  
Embryo Development ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Interaction Network ◽  
Enrichment Analysis ◽  
Ovis Aries ◽  
Functional Enrichment ◽  
Saga Complex ◽  
Rna Seq ◽  
Estrus Phase

Abstract Background:In sheep, FecB is the essential biomarker of the fertility, previous researches have provided a detailed insight on the regulation involved estrus phase and FecB in the reproductive-related tissues including hypothalamus, pituitary, and ovary. However, as the host of embryo development and connection between the ovary and the uterus, little is known about the interaction between mRNAs and lncRNAs in sheep oviduct. In the present study, RNA-Seq was performed to identify the transcriptomic profiles of mRNAs and lncRNAs in oviduct during estrus phase of sheep with FecBBB/++ genotypes.Results:In total, 21,863 lncRNAs and 43,674 mRNAs were identified, 57 DE lncRNAs and 637 DE mRNAs were revealed in the comparisons between follicular phase and luteal phase, 26 DE lncRNAs and 421 DE lncRNAs were revealed in the comparisons between FecB BB genotype and FecB ++ genotype. Functional enrichment analysis suggested that GO and KEGG terms related to reproduction such as SAGA complex, ATP-binding cassette (ABC), Nestin, and Hippo signalling pathway. DE-interaction network suggested that LNC_018420 maybe the key regulators related to embryo development in sheep oviduct.Conclusion:This was the first study to reveal the transcriptomic profiles of mRNAs and lncRNAs in the oviduct of FecB BB/++ sheep at estrus phase using RNA-Seq. Our findings can provide new understanding on the molecular mechanisms of mRNAs and lncRNAs underlying sheep embryo development and also opening new lines of investigation in sheep reproduction.

Immune Infiltration in Gastric Cancer Microenvironment and Its Clinical Significance

2020 ◽  
Author(s):  
An Zhi Zhang ◽  
Xin Yuan ◽  
Ya Li ◽  
Yu Fang Xie ◽  
Jiang Fen Li ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
T Cells ◽  
Immune Cells ◽  
Expression Profiles ◽  
Tnm Staging ◽  
Functional Enrichment ◽  
Cancer Tissue ◽  
Fuhrman Grade ◽  
Cytokine Activation ◽  
Immune Related Genes

Abstract Background In recent years, immunotherapy has developed rapidly and has gradually become one of the important methods for treatment of gastric cancer. The research on immune cells and immune-related genes in the tumor microenvironment greatly encourages the development of immunotherapy. Methods : The devolution algorithm (CIBERSORT) was applied to infer the proportion of 22 immune infiltrating cells based on gene expression profiles of gastric cancer tissue, which were downloaded from TCGA and GEO databases. The TCGA database was utilized to analyze the differential expression of immune-related genes, and explore the potential molecular functions of these genes.ResultsWe have observed the enrichment of multiple immune cells in the microenvironment of gastric cancer. Some of these cells are closely related to Fuhrman grade and TNM staging. Survival analysis showed that the infiltration level of CD8 + T cells, activated CD4 + memory T cells and M2 macrophages was significantly related to the prognosis of gastric cancer patients. The functional enrichment analysis of immune-related genes revealed that these genes were mainly associated with cytokine activation and response. Four significant modules were screened by PPI network and 20 key genes were screened from the modules, and the expression levels of CALCR and PTH1R are strikingly related to the prognosis of gastric cancer patients.ConclusionsThe type and number of infiltrating immune cells in the microenvironment of gastric cancer, as well as immune-related genes are closely related to tumor progression, and can be used as important indicators for patient prognosis assessment.

scholarly journals Cross-sectional study of human coding- and non-coding RNAs in progressive stages of Helicobacter pylori infection

2020 ◽  
Vol 7 (1) ◽  
Author(s):  
Sergio Lario ◽  
María J. Ramírez-Lázaro ◽  
Aintzane González-Lahera ◽  
José L. Lavín ◽  
Maria Vila-Casadesús ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Expression Profiles ◽  
Gastric Carcinogenesis ◽  
Individual Response ◽  
Peptic Ulcers ◽  
Gastric Diseases ◽  
Sequence Of Events ◽  
Non Coding Rnas ◽  
H Pylori

Abstract Helicobacter pylori infects 4.4 billion individuals worldwide and is considered the most important etiologic agent for peptic ulcers and gastric cancer. Individual response to H. pylori infection is complex and depends on complex interactions between host and environmental factors. The pathway towards gastric cancer is a sequence of events known as Correa’s model of gastric carcinogenesis, a stepwise inflammatory process from normal mucosa to chronic-active gastritis, atrophy, metaplasia and gastric adenocarcinoma. This study examines gastric clinical specimens representing different steps of the Correa pathway with the aim of identifying the expression profiles of coding- and non-coding RNAs that may have a role in Correa’s model of gastric carcinogenesis. We screened for differentially expressed genes in gastric biopsies by employing RNAseq, microarrays and qRT-PCR. Here we provide a detailed description of the experiments, methods and results generated. The datasets may help other scientists and clinicians to find new clues to the pathogenesis of H. pylori and the mechanisms of progression of the infection to more severe gastric diseases. Data is available via ArrayExpress.

scholarly journals Identification of a molecular signature of prognostic subtypes in diffuse-type gastric cancer

2019 ◽  
Vol 23 (3) ◽  
pp. 473-482 ◽  
Author(s):  
Seon-Kyu Kim ◽  
Hee-Jin Kim ◽  
Jong-Lyul Park ◽  
Haejeong Heo ◽  
Seon-Young Kim ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Tissue Microarray ◽  
Microarray Analysis ◽  
Cox Regression ◽  
Molecular Signature ◽  
Diffuse Type ◽  
Rna Seq ◽  
Tissue Samples ◽  
Diffuse Type Gastric Cancer ◽  
Tissue Microarray Analysis

Abstract Background Although recent advances in high-throughput technology have provided many insights into gastric cancer (GC), few reliable biomarkers for diffuse-type GC have been identified. Here, we aim to identify a prognostic and predictive signature of diffuse-type GC heterogeneity. Methods We analyzed RNA-seq-based transcriptome data to identify a molecular signature in 150 gastric tissue samples including 107 diffuse-type GCs. The predictive value of the signature was verified using other diffuse-type GC samples in three independent cohorts (n = 466). Log-rank and Cox regression analyses were used to estimate the association between the signature and prognosis. The signature was also characterized by somatic variant analyses and tissue microarray analysis between diffuse-type GC subtypes. Results Transcriptomic profiling of RNA-seq data identified a signature which revealed distinct subtypes of diffuse-type GC: the intestinal-like (INT) and core diffuse-type (COD) subtypes. The signature showed high predictability and independent clinical utility in diffuse-type GC prognosis in other patient cohorts (HR 2.058, 95% CI 1.53–2.77, P = 1.76 × 10–6). Integrative mutational and gene expression analyses demonstrated that the COD subtype was responsive to chemotherapy, whereas the INT subtype was responsive to immunotherapy with an immune checkpoint inhibitor (ICI). Tissue microarray analysis showed the practical utility of IGF1 and NXPE2 for predicting diffuse-type GC heterogeneity. Conclusions We present a molecular signature that can identify diffuse-type GC patients who display different clinical behaviors as well as responses to chemotherapy or ICI treatment.

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