Circular RNA in gastric cancer.
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ABSTRACT:
SUBMITTER: Li XW
PROVIDER: S-EPMC7470003 | biostudies-literature | 2020 Aug
REPOSITORIES: biostudies-literature
Publications
Circular RNA in gastric cancer.
Li Xue-Wei XW Yang Wen-Hui WH Xu Jun J
Chinese medical journal 20200801 15
Gastric cancer (GC) is a common malignancy and is the third leading cause of cancer-related death. At present, there is no simple and effective screening method for early-stage GC, and the treatment results and prognosis are poor. With the continuous improvement of molecular biology techniques, research on circular RNA (circRNA) has gradually expanded over time. Much data supports the role of circRNA in tumorigenesis. Moreover, due to its structural specificity and biological stability, circRNA ...[more]
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Project description:BackgroundRecent studies have indicated that circular RNAs (circRNAs) are novel endogenous RNAs whose 5' and 3' ends are covalently linked and play critical roles in gastric carcinogenesis. However, the significance of circRNA hsa_circ_0001874 in gastric cancer (GC) is still unclear.MethodsTherefore, we first detected hsa_circ_0001874 levels in GC cell lines and tissues and analyzed their potential correlation with clinicopathological factors. Then, a receiver operating characteristic (ROC) curve was established to evaluate its clinical value. Finally, we further predicted the biological functions of this molecule by bioinformatics analysis.ResultsOur data showed that as an indicator, hsa_circ_0001874 expression was significantly decreased in 78.02% (71/91) of the GC patients. Combined with clinicopathological factors, the hsa_circ_0001874 level was strongly associated with cell differentiation (p < 0.001), tumor stage (p = 0.005), invasion (p = 0.024), lymphatic metastasis (p = 0.023), and CEA level (p < 0.001) in GC tissues. The area under the curve (AUC) was up to 0.673, with a sensitivity and specificity of 61.54% and 68.13%, respectively. Bioinformatics analysis showed that hsa_circ_0001874 harbors miR-593-5p, miR-103a-3p, and miR-107 seed sequences to regulate these three miRNAs and downstream target genes and exert its various biological functions in the carcinogenesis and progression of GC.ConclusionIn summary, these data suggest that hsa_circ_0001874 is an indicator of GC and plays a significant role in gastric carcinogenesis and progression.
| S-EPMC8274977 | biostudies-literature
Project description:Circular RNAs (circRNAs) are a class of non-coding RNAs broadly expressed in cells of various species. Their role in cancers, especially in gastric cancer, is poorly understood.Circular RNA 0000096 (hsa_circ_0000096) levels in 101 paired gastric cancer tissues and adjacent non-tumorous tissues from patients with gastric cancer were detected by real-time quantitative reverse transcription-polymerase chain reaction. A receiver operating characteristic curve was generated to evaluate the diagnostic value of hsa_circ_0000096. RNA interference was used to manipulate the expression of hsa_circ_0000096. Its biological effects were evaluated by flow cytometry, real-time cell analysis, a wound scratch assay, western blot analysis and xenograft models.Hsa_circ_0000096 was found to be significantly downregulated in gastric cancer tissues and gastric cancer cell lines compared with paired adjacent non-tumorous tissues and normal gastric epithelial cells (P<0.001). Moreover, knockdown of hsa_circ_0000096 significantly inhibited cell proliferation and migration in vitro and in vivo. The results of both immunohistochemical and western blot analyses showed that the protein levels of cyclin D1, cyclin-dependent kinase 6 (CDK6), matrix metalloproteinase-2 and MMP-9 were significantly reduced in vitro and in vivo. A gastric cancer xenograft nude mouse model indicated that Ki67 and VEGF were reduced in a dose-dependent manner following knockdown of hsa_circ_0000096. However, the expression of E-cadherin increased.Hsa_circ_0000096 may be used as a potential novel biomarker for gastric cancer. It affects gastric cancer cell growth and migration by regulating cyclin D1, CDK6, MMP-2 and MMP-9.
| S-EPMC5344286 | biostudies-literature
Project description:Gastric cancer (GC) is among the most common cancer types worldwide with high mortality. Recent studies have shown that exosomes play a crucial role in the tumorigenesis of GC. The present study aimed to investigate the circular RNA (circRNA) profile in plasma exosomes from patients with gastric cancer (GC). Peripheral blood samples were collected from 5 patients with GC and 5 healthy donors, and exosomes were isolated from plasma. The high-throughput RNA sequencing (RNA-seq) method was applied to detect the differently expressed circRNAs (DE circRNAs). Subsequently, sequencing results were confirmed by reverse transcription quantitative (RT-q) PCR. The potential roles of DE circRNAs in GC were identified using Gene ontology (GO) and Kyoto Encyclopedia of Gene and Genome (KEGG) analysis. Furthermore, MiRanda software was used to predict circRNA-micro-RNA (miRNA) interactions. A total of 67,880 circRNAs were identified in all samples and 1,060 significantly DE circRNAs were screened, including 620 upregulated and 440 downregulated ones. These results were further confirmed by RT-qPCR. GO and KEGG analyses revealed that these circRNAs were significantly associated with 'cell cycle', 'cytoskeleton organization', 'cellular response to DNA damage', 'regulation of GTPase activity', 'phosphatidylinositol signaling pathway', 'MAPK signaling pathway', 'thyroid hormone signaling pathway', 'chemokine signaling pathway' and 'Wnt signaling pathway'. In addition, a circRNA-miRNA-mRNA interaction network was established. Taken together, these findings may help better understanding the underlying mechanisms of GC and identifying new molecular alterations in GC, and allow the enrichment of the circRNA profiling in human GC.
| S-EPMC7403632 | biostudies-literature
Project description:BackgroundCircular RNAs (circRNAs) are recently found involved in cancer occurrence and development. However, their values in the diagnosis of gastric cancers are largely unknown. In this study, we analyzed the values of hsa_circ_0000181 in the diagnosis of gastric cancer.MethodsUsing divergent primers, hsa_circ_0000181 expression levels in fresh gastric cancer tissues and paired adjacent non-tumorous tissues, and plasmas from patient with gastric cancer and health people were detected by real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The association between hsa_circ_0000181 levels and the clinicopathologic features of patients with gastric cancer was further analyzed. Finally, to evaluate the diagnostic value, receiver operating characteristic (ROC) curve was established.ResultsHsa_circ_0000181 levels in gastric cancer tissues and plasma from gastric cancer patients were significantly decreased than those in paired adjacent non-tumorous tissues (P < .001) and healthy people (P < .001), respectively. Furthermore, hsa_circ_0000181 expression in gastric cancer tissues was significantly correlated with tumor diameter (P = .027), lymphatic metastasis (P = .044), distal metastasis (P = .023), and carbohydrate antigen 19-9 (P = .031). Its decreased levels in patients' plasma were significantly associated with differentiation (P = .038) and carcinoembryonic antigen (P = .037). The areas under ROC curve were 0.756. The specificity of tissue hsa_circ_0000181 and sensitivity of plasma hsa_circ_0000181 were 85.2% and 99.0%, respectively.ConclusionsThanks to the high stability, tissue and plasma hsa_circ_0000181 may be a novel biomarker for the diagnosis of gastric cancer.
| S-EPMC6817246 | biostudies-literature
Project description: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.
| S-EPMC5878900 | biostudies-literature
Project description:BackgroundIn gastric cancer (GC), circular RNAs (circRNAs) mainly play an important role in miRNA sponge, which not only indicate long-term survival and prognosis but also increase resistance to the apoptosis. The purpose of the study is to explore new circRNAs and their underlying mechanisms in GC.MethodThrough rigorous retrieval strategies, we used the sva package to analyze and identify differentially expressed circRNAs (DECs) from three Gene Expression Omnibus microarray datasets (GSE83521, GSE89143, and GSE78092). Online website CSCD and CircInteractome were used to reveal the binding sites between miRNAs and DECs. The possible target miRNAs of the DECs identified based on miRNAs, and Cytoscape was used to create a regulatory network of circRNA-miRNA-mRNA and identified the hub genes which were further validated using The Cancer Genome Atlas database and Human Protein Atlas.ResultsTwenty-eight DECs were obtained using the sva package. A regulatory network of circRNA-miRNA-mRNA (competing endogenous RNA) containing 15 circRNAs, 24 miRNAs, and 158 genes was identified. A protein-protein interaction network based on the 158 genes was established, and further determined that 10 hub genes (SKA1, ANLN, CHEK1, SKA3, TOP2A, BIRC5, RRM2, NCAPG2, FANCI, and RAD51) were associated with some cancer-related pathways based on the functional enrichment analysis. Finally, six hub genes (BIRC5, TOP2A, FANCI, NCAPG2, RAD51, and RRM2) were proven to influence the overall survival of GC.ConclusionOur study established a circRNA-miRNA-mRNA regulatory network and defined six circRNA-related hub genes in GC, which could serve as potential therapeutic targets or prognostic biomarker for GC treatment.
| S-EPMC7666747 | biostudies-literature
Project description:BackgroundBerberine has been demonstrated to have anticancer effects against gastric cancer (GC), but the mechanism of these actions is unclear.ObjectivesTo explore the impact of berberine on circular RNA (circRNA) expression profiles in GC and investigate the potential molecular mechanisms associated with circRNAs in GC.MethodsAGS and HGC27 GC cells were treated with various concentrations of berberine. Cell viability was measured using a Cell Counting Kit-8 assay. Cell proliferation was measured using a cell colony formation assay. Cell apoptosis was measured using flow cytometry. The mitochondrial membrane potential (Δψm) was determined using a JC-1 probe. RNA-seq was performed to identify circRNA expression profiles in AGS cells after berberine treatment. Selected differentially expressed (DE) circRNAs were verified using RT-qPCR. Bioinformatics analysis was performed to predict target miRNAs and mRNAs and construct a circRNA-miRNA-mRNA network. Pathway and process enrichment analyses were performed to explore the potential biological roles of DE circRNAs.ResultsBerberine decreased GC cell viability, cell proliferation, and Δψm and induced cell apoptosis. Thirty-one DE circRNAs were identified in the berberine-treated group compared to the control group, among which circRNA2499, hsa_circ_0003423, and hsa_circ_0006702 were validated using RT-qPCR. Enrichment analyses, based on the host genes of these 31 DE circRNAs and putative target mRNAs in the circRNA-miRNA-mRNA network of the validated circRNAs, indicated that berberine exerts anti-GC effects in multiple pathways including the Notch, MAPK, and NF-κB signaling pathways via specific circRNAs.ConclusionThis study elucidated the expression profile of circRNAs in human GC cells after berberine treatment. Our results demonstrate that berberine has the potential to influence cancer-related pathways by regulating circRNA expression and their corresponding target genes in GC cells.
| S-EPMC8112944 | biostudies-literature
Project description:BackgroundAccumulating evidences have shown that circular RNAs (circRNAs) play important roles in regulating the pathogenesis of cancer. However, the role of circRNAs in gastric cancer (GC) remains largely unclear.MethodsIn this study, we identified a novel upregulated circRNA, hsa_circ_0001829, in chemically induced malignant transformed human gastric epithelial cells using RNA-seq. Subsequent qRT-PCR and ISH assays were performed to detect the expression level of hsa_circ_0001829 in GC cell lines and tissues. Functional roles of hsa_circ_0001829 in GC were then explored by loss- and gain-of- function assays. Bioinformatic prediction and luciferase assay were used to investigate potential mechanisms of hsa_circ_0001829. Finally, the mice xenograft and metastasis models were constructed to assess the function of hsa_circ_0001829 in vivo.ResultsWe found that hsa_circ_0001829 was significantly upregulated in GC tissues and cell lines. Loss- and gain-of- function assays showed that hsa_circ_0001829 promotes GC cells proliferation, migration and invasion, and the affected cell cycle progression and apoptosis rates may account for the effect of hsa_circ_0001829 on GC proliferation. In addition, bioinformatic prediction and luciferase assay showed that hsa_circ_0001829 acts as a molecular sponge for miR-155-5p and that SMAD2 was a target gene of miR-155-5p; moreover, hsa_circ_0001829 sponges miR-155-5p to regulate SMAD2 expression and hsa_circ_0001829 promotes GC progression through the miR-155-5p-SMAD2 pathway. Finally, suppression of hsa_circ_0001829 expression inhibited tumor growth and aggressiveness in vivo.ConclusionTaken together, our findings firstly demonstrated a novel oncogenic role of hsa_circ_0001829 in GC progression through miR-155-5p-SMAD2 axis, and our study may offer novel biomarkers and therapeutic targets for GC.
| S-EPMC7731483 | biostudies-literature
Project description:Circular RNAs (circRNAs) are a new class of noncoding RNAs. However, the expression profile and clinical significance of circRNAs in human gastric cancer is unclear. The global circRNA expression profile in human gastric cancer was measured by circRNA microarray. Hsa_circ_0014717, one of the most downregulated circRNAs in microarray, was selected as a targeted circRNA to explore its levels in gastric tissues and gastric juice. Freeze-thaw experiment and incubation experiment confirmed the stability of gastric juice circRNAs. A total of 308 circRNAs, including 107 (34.74%) upregulated and 201 (65.26%) downregulated circRNAs, were found significantly aberrantly expressed in gastric cancer tissues. The top ten upregulated in gastric cancer tissues were hsa_circ_0035445, hsa_circ_0003789, hsa_circ_0063809, hsa_circ_0074362, hsa_circ_0006282, hsa_circ_0011107, hsa_circ_0084606, hsa_circ_0005556, hsa_circ_0050547, and hsa_circ_0006470, while the top ten downregulated ones were hsa_circ_0007099, hsa_circ_0001897, hsa_circ_0007707, hsa_circ_0008832, hsa_circ_0001546, hsa_circ_0002089, hsa_circ_0004680, hsa_circ_0000154, hsa_circ_0004458, and hsa_circ_0008394. The hot-point chromosomes were chr1, chr2, chr3, chr9, and chr17. Hsa_circ_0014717 was significantly downregulated in 77.2% (74/96) gastric cancer tissues. Its levels in gastric cancer tissues were related to tumor stage (P = 0.037), distal metastasis (P = 0.048), tissue carcinoembryonic antigen (P = 0.001), and carbohydrate antigen 19-9 expression (P = 0.021). More importantly, hsa_circ_0014717 can stably exist in human gastric juice; and its nature meets the requirements of clinical detection. Our study uncovered the circRNA expression profile in human gastric cancer. Moreover, some circRNAs can stably exist in human body fluid, and has the potential to be used as novel biomarkers for the screening of high-risk gastric cancer patients.
| S-EPMC5463069 | biostudies-literature
Project description:Cancer stem cells (CSCs) are cancer initiating cells that are not only a source of tumorigenesis but also the cause of tumour progression, metastasis and therapy resistance. EBV-associated gastric cancer (EBVaGC) is a distinct subtype of gastric cancer with unique clinicopathological and molecular features. However, whether CSCs exist in EBVaGC, and the tumorigenic mechanism of EBV, remains unclear. Here, NOD/SCID mice were injected subcutaneously with the EBVaGC cell line SNU719 and treated with 5-fluorouracil weekly. Successive generations of xenografts yielded a highly malignant EBVaGC cell line, SNU-4th, which displays properties of CSCs and mainly consists of CD44+CD24- cells. In SNU-4th cells, the expression of an EBV-encoded circRNA, ebv-circLMP2A, is strongly increases, which plays crucial roles in inducing and maintaining stemness phenotypes by targeting the miR-3908/TRIM59/p53 axis. Additionally, high expression of ebv-circLMP2A is significantly associated with metastasis and poor prognosis in patients with EBVaGC. These findings not only provide evidence for the existence of CSCs in EBVaGC and elucidate the pathogenic mechanism of ebv-circLMP2A in EBVaGC, but also provide a promising therapeutic target for EBVaGC.
| S-SCDT-EMBOR-2019-49689V1 | biostudies-other