Unearthing Regulatory Axes of Breast Cancer circRNAs Networks to Find Novel Targets and Fathom Pivotal Mechanisms

Afzali, Farzaneh; Salimi, Mahdieh

doi:10.1007/s12539-019-00339-6

Cited by 32 publications

(16 citation statements)

References 72 publications

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“…In our study, we identified 4 DEcircRNAs in the circRNA-miRNA- hub_gene network and found that hsa_circ_0001666 was downregulated in CRC tissues. This result is consistent with a recent study (30) indicating that hsa_circ_0001666 was downregulated in breast cancer tissues and may therefore play a key role in the development of breast malignancies. However, other circRNAs discovered in our ceRNA network have not been reported previously.…”

Section: Discussionsupporting

confidence: 93%

Circular RNA-Associated Competing Endogenous RNA Network and Prognostic Nomogram for Patients With Colorectal Cancer

Song

2019

Front. Oncol.

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Background: Genetic characteristics remain underutilized for establishing prognostic models for colorectal cancer (CRC). We explored the underlying regulatory mechanisms of circular RNAs (circRNAs) that act as competing endogenous RNAs (ceRNAs) and constructed a gene-based nomogram to predict overall survival (OS) in patients with CRC.Methods: We obtained circRNA expression profiling data from the Gene Expression Omnibus (GEO) database. MicroRNA (miRNA) and mRNA expression profiles, with associated clinical data, were obtained from The Cancer Genome Atlas (TCGA). A ceRNA network was established using Cytoscape. Interactions between differential genes were analyzed, and hub genes were identified using the cytoHubba application. The R package “clusterProfiler” was used to evaluate the Gene Ontology (GO) annotations of the differentially expressed mRNAs and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Database-extracted patients were randomized into a training and validation cohorts. A prognostic model was developed using the training set based on multivariate Cox analyses and was then assessed in the validation set. The accuracy of the model was evaluated using discrimination and calibration plots.Results: Thirteen circRNAs, 62 miRNAs, and 301 mRNAs were used to construct the ceRNA network; 10 hub genes were identified via the PPI network. Next, a circRNA- miRNA hub of gene-regulatory modules was established based on four differentially expressed circRNAs, eight differentially expressed miRNAs, and nine differentially expressed mRNAs (DEmRNAs). GO and KEGG pathway analyses indicated the possible association of DEmRNAs with CRC onset and progression. Multivariate analyses revealed that age, tumor stage, and CXCR5 expression were independent risk factors for OS. A CXCR5-based model was developed to predict the OS of patients with CRC in our training set. Our nomogram showed relatively good accuracy, with C-indices of 0.757 and 0.702 in the training and validation sets, respectively. The areas under the curve of the nomograms predicting 3- and 5-years OS were 0.749 and 0.805 in the training set and 0.706 and 0.779 in the validation set, respectively.Conclusions: Our data suggested that the hsa_circ_00001666/has-mir-1229/CXCR5 axis plays an important role in the pathogenesis of CRC, thereby identifying a potential therapeutic target. The proposed CXCR5-based nomogram may also assist surgeons in devising personalized treatments for patients with this disease.

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Section: Discussionsupporting

confidence: 93%

Circular RNA-Associated Competing Endogenous RNA Network and Prognostic Nomogram for Patients With Colorectal Cancer

Song

2019

Front. Oncol.

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“…For example, miR-145-5p inhibited growth, migration and invasion of CRC [21,22]. Silencing miR-135b-5p sensitized CRC cells to oxaliplatin-induced apoptosis by upregulating FOXO1 expression [23].…”

Section: Discussionmentioning

confidence: 99%

Whole-transcriptome analysis reveals a potential hsa_circ_0001955/hsa_circ_0000977-mediated miRNA-mRNA regulatory sub-network in colorectal cancer

Ding

Yao

Fan

et al. 2020

Aging

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Background: Circular RNAs (circRNAs), a novel class of non-coding RNAs, have been found to act as microRNA (miRNA) sponges and thus play key roles in biological processes and pathogenesis. However, studies regarding circRNAs in colorectal cancer (CRC) remain inadequate. Results: By differential expression analysis, 10 candidate circRNAs (6 upregulated and 4 downregulated circRNAs) were chosen. 9 of 10 circRNAs were available on CSCD and their structure showed the binding potential of miRNA. Intersection analysis revealed that miR-145-5p, miR-3127-5p, miR-761, miR-4766-3p, miR-135a-5p, miR-135b-5p, miR-374a-3p and miR-330-3p were 8 miRNAs with the most potential in binding circRNAs. Further expression validation and correlation analysis demonstrated hsa_circ_0001955/miR-145-5p and hsa_circ_0000977/miR-135b-5p axes as key pathways in CRC. Subsequently, target gene prediction, differential expression analysis, intersection analysis and correlation analysis showed that CDK6, MMP12 and RAB3IP were the three potential downstream targets of hsa_circ_0001955/miR-145-5p axis and FOXO1, MBNL1, MEF2C, RECK, PPM1E, TTLL7 and PCP4L1 were the seven potential downstream targets of hsa_circ_0000977/miR-135b-5p axis in CRC. Finally, we also confirmed that expression of hsa_circ_0001955 or hsa_circ_0000977 was significantly positively correlated with their individual targets in CRC. Conclusions: In the present work, we constructed a potential hsa_circ_0001955/hsa_circ_0000977-mediated circRNA-miRNA-mRNA regulatory network in CRC by a series of in silico analysis and experimental validation. Methods: Whole-transcriptome microarrays from CRC and matched normal samples were obtained from GEO. The structure of circRNA was identified by CSCD. starBase and miRNet were successively used to predict miRNA of circRNA and target gene of miRNA. Expression correlation between RNA-RNA interactions was assessed using GEO and TCGA data. Finally, a potential circRNA-miRNA-mRNA network was established based on competing endogenous RNA (ceRNA) hypothesis.

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“…Analysis of circulating microRNAs (cmiRNAs) before surgical operation (BSO) and after the surgical operation (ASO) has provided significant information for NSCLC diagnosis, progression, and outcomes of treatment [2]. One of the epigenetic biomarkers, known as cmiRNA, serves as a potential source for diagnosing NSCLC and its subtypes [3][4][5][6]. There are three important advantages in using cmiRNAs as a biomarker for NSCLC; they are as follows: (1) diagnostic feasibility from body fluids, (2) elevated stability and protection from endogenous enzymes (RNAase), and (3) accumulation of pathologic information from various tumorous sites, which overcomes the difficulty of tumor heterogenicity [7].…”

Section: Introductionmentioning

confidence: 99%

Circulating miR-1246 Targeting UBE2C, TNNI3, TRAIP, UCHL1 Genes and Key Pathways as a Potential Biomarker for Lung Adenocarcinoma: Integrated Biological Network Analysis

Huang

Wei

Kaliamurthi

et al. 2020

JPM

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Analysis of circulating miRNAs (cmiRNAs) before surgical operation (BSO) and after the surgical operation (ASO) has been informative for lung adenocarcinoma (LUAD) diagnosis, progression, and outcomes of treatment. Thus, we performed a biological network analysis to identify the potential target genes (PTGs) of the overexpressed cmiRNA signatures from LUAD samples that had undergone surgical therapy. Differential expression (DE) analysis of microarray datasets, including cmiRNAs (GSE137140) and cmRNAs (GSE69732), was conducted using the Limma package. cmiR-1246 was predicted as a significantly upregulated cmiRNA of LUAD samples BSO and ASO. Then, 9802 miR-1246 target genes (TGs) were predicted using 12 TG prediction platforms (MiRWalk, miRDB, and TargetScan). Briefly, 425 highly expressed overlapping miRNA-1246 TGs were observed between the prediction platform and the cmiRNA dataset. ClueGO predicted cell projection morphogenesis, chemosensory behavior, and glycosaminoglycan binding, and the PI3K–Akt signaling pathways were enriched metabolic interactions regulating miRNA-1245 overlapping TGs in LUAD. Using 425 overlapping miR-1246 TGs, a protein–protein interaction network was constructed. Then, 12 PTGs of three different Walktrap modules were identified; among them, ubiquitin-conjugating enzyme E2C (UBE2C), troponin T1(TNNT1), T-cell receptor alpha locus interacting protein (TRAIP), and ubiquitin c-terminal hydrolase L1(UCHL1) were positively correlated with miR-1246, and the high expression of these genes was associated with better overall survival of LUAD. We conclude that PTGs of cmiRNA-1246 and key pathways, namely, ubiquitin-mediated proteolysis, glycosaminoglycan binding, the DNA metabolic process, and the PI3K–Akt–mTOR signaling pathway, the neurotrophin and cardiomyopathy signaling pathway, and the MAPK signaling pathway provide new insights on a noninvasive prognostic biomarker for LUAD.

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Unearthing Regulatory Axes of Breast Cancer circRNAs Networks to Find Novel Targets and Fathom Pivotal Mechanisms

Cited by 32 publications

References 72 publications

Circular RNA-Associated Competing Endogenous RNA Network and Prognostic Nomogram for Patients With Colorectal Cancer

Circular RNA-Associated Competing Endogenous RNA Network and Prognostic Nomogram for Patients With Colorectal Cancer

Whole-transcriptome analysis reveals a potential hsa_circ_0001955/hsa_circ_0000977-mediated miRNA-mRNA regulatory sub-network in colorectal cancer

Circulating miR-1246 Targeting UBE2C, TNNI3, TRAIP, UCHL1 Genes and Key Pathways as a Potential Biomarker for Lung Adenocarcinoma: Integrated Biological Network Analysis

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