Dataset Information

Circular RNA profile of parathyroid neoplasms: analysis of co-expression networks of circular RNAs and mRNAs.

ABSTRACT: Circular RNAs (circRNAs) are a recently identified class of non-coding RNAs that participate in multiple biological processes and tumour progression. However, circRNA expression pattern in parathyroid neoplasms remains unknown. The circRNA profile of 6 parathyroid carcinomas (PCs), 6 parathyroid adenomas (PAs) and 4 normal parathyroid tissues was assessed by a microarray. Bioinformatic analyses were performed to investigate potential core circRNAs via co-expression network. CircRNA and corresponding mRNA expression were validated in a cohort of parathyroid neoplasms by RT-qPCR and fluorescence in situ hybridization (FISH). Compared to normal parathyroid, 5310 and 1055 circRNAs were differentially expressed in PC and PA tissues, respectively. The differential expression of 4 circRNAs (hsa_circRNA_0035563 (p = 0.006), hsa_circRNA_0017545 (p = 0.009), hsa_circRNA_0001687 (p = 0.005) and hsa_circRNA_0075005 (p = 0.001)) and 4 mRNAs (MYC, FSCN1, ANXA2 and AKR1C3) between PC and PA tissues were confirmed by RT-qPCR. In addition, high expression of hsa_circ_0035563 was related to CDC73 mutations (p = 0.022) and recurrence in PC patients (p = 0.042). Furthermore, hsa_circ_0075005 helped distinguish PCs from benign lesions using FISH, and the area under the curve was 0.779 (p = 0.013). Our findings describe the circRNA profile of PC for the first time and suggest that circRNAs and mRNAs interact in parathyroid tumourigenesis. This study demonstrates that hsa_circ_0075005 and MYC mRNA may be used for the differential diagnosis of PC and PA. The expression levels of hsa_circ_0035563 are related to CDC73 mutations and recurrence in malignancy, highlighting the significance of this parameter in prognosis of PC patients.

SUBMITTER: Hu Y

PROVIDER: S-EPMC6693544 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Circular RNA profile of parathyroid neoplasms: analysis of co-expression networks of circular RNAs and mRNAs.

Hu Ya Y Zhang Xiang X Cui Ming M Wang Mengyi M Su Zhe Z Liao Quan Q Zhao Yupei Y

RNA biology 20190618 9

Circular RNAs (circRNAs) are a recently identified class of non-coding RNAs that participate in multiple biological processes and tumour progression. However, circRNA expression pattern in parathyroid neoplasms remains unknown. The circRNA profile of 6 parathyroid carcinomas (PCs), 6 parathyroid adenomas (PAs) and 4 normal parathyroid tissues was assessed by a microarray. Bioinformatic analyses were performed to investigate potential core circRNAs via co-expression network. CircRNA and correspon ...[more]

PMID: 31213128

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Project description:BackgroundCircular RNAs (circRNAs) and long non-coding RNAs (lncRNAs) have been recently identified as new classes of non-coding RNAs which participate in carcinogenesis and tumor progression. However, the functions of these non-coding RNAs and gene expression patterns are largely unknown.MethodsWe carried out high-throughput sequencing to analyze the differential expression of RNAs in 5 coupled laryngeal cancer (LC) and corresponding adjacent noncancerous tissues. Bioinformatics analyses were performed to predict the functions of these non-coding RNAs via co-expression, competing endogenous RNA networks and pathway enrichment analysis. The differential expression of the selected RNAs were confirmed using RT-qPCR. The CCK8, EDU, Transwell, and wound healing assays were conducted to validate the biological functions of SNHG29 in LC. Western blot assay was performed to identify the effects of SNHG29 having on the epithelial to mesenchymal transition process. Kaplan-Meier analysis was used to investigate whether the expression level of SNHG29 correlated with survival in LC patients. One-way ANOVA was used to analyze the correlation between the expression of SNHG29 and clinicopathological parameters of the included patients.ResultsCompared to normal laryngeal tissues, 31,763 non-coding RNAs were upregulated and 11,557 non-coding RNAs were downregulated in cancer tissues. SNHG29 expression was low in the LC cell lines and tissues predicting a better clinical prognosis. SNHG29 was also found to inhibit the proliferation, migration, and invasion ability of LC, exerting a suppressive role in the epithelial to mesenchymal transition process as well. SNHG29 downregulation was significantly correlated with differentiation (P=0.026), T-stage (P=0.041), lymphatic metastasis (P=0.044), and clinical stage (P=0.037). We found that the biological functions of differentially expressed transcripts included cell adhesion, biological adhesion, and migration and invasion related to adherens junction pathways.ConclusionsOur study was the first to describe the non-coding RNA profile of LC, and suggested that dysregulated non-coding RNAs could be involved in LC tumorigenesis. SNHG29 was demonstrated to play crucial roles in inhibiting the pathogenesis and progression of LC. Our findings provide a new approach for further analyses of pathogenetic mechanisms, the detection of novel transcripts, and the identification of valuable biomarkers for this tumor.

Project description:BackgroundThe brown adipose tissue (BAT) is a target for treating obesity. BAT losses thermogenic capacity and gains a "white adipose tissue-like" phenotype ("BAT whitening") under thermoneutral environments, which is a potential factor causing a low curative effect in BAT-related obesity treatments. Circular RNAs (circRNAs) and long non-coding RNAs (lncRNAs) can act as competing endogenous RNAs (ceRNA) to mRNAs and function in various processes by sponging shared microRNAs (miRNAs). However, the roles of circRNA- and lncRNA-related ceRNA networks in regulating BAT whitening remain litter known.ResultsIn this study, BATs were collected from rabbits at day0 (D0), D15, D85, and 2 years (Y2). MiRNA-seq was performed to investigate miRNA changes during BAT whitening. Then, a combined analysis of circRNA-seq and whole-transcriptome sequencing was used for circRNA assembly and quantification during BAT whitening. Our data showed that 1187 miRNAs and 6204 circRNAs were expressed in the samples, and many of which were identified as significantly changed during BAT whitening. Target prediction showed that D0-selective miRNAs were significantly enriched in the Ras, MAPK, and PI3K-Akt signaling pathways, and Y2-selective miRNAs were predicted to be involved in cell proliferation. The cyclization of several circRNAs could form novel response elements of key thermogenesis miRNAs at the back-splicing junction (BSJ) sites, and in combination with a dual-luciferase reporter assay confirmed the binding between the BSJ site of novel_circ_0013792 and ocu-miR-378-5p. CircRNAs and lncRNAs have high cooperativity in sponging miRNAs during BAT whitening. Both circRNA-miRNA-mRNA and lncRNA-miRNA-mRNA triple networks were significantly involved in immune response-associated biological processes. The D15-selective circRNA might promote BAT whitening by increasing the expression of IDH2. The Y2-selective circRNA-related ceRNA network and lncRNA-related ceRNA network might regulate the formation of the WAT-like phenotype of BAT via MAPK and Ras signaling pathways, respectively.ConclusionsOur work systematically revealed ceRNA networks during BAT whitening in rabbits and might provide new insight into BAT-based obesity treatments.

Project description:BackgroundCircular RNAs (circRNAs) are involved in the pathogenesis of several diseases. Among oral maxillofacial cancers, oral squamous cell carcinoma (OSCC) has the highest incidence. However, the role of circRNAs in OSCC is still not clear. The aim of our study was to evaluate the circRNA expression profile in OSCC and explore further the potential role of circRNAs in the pathogenesis of OSCC.MethodsCircRNA sequencing was performed in 6 pairs of samples of OSCC and normal oral mucosal tissues. Expression of selected circRNAs was validated by qRT-PCR. GO and KEGG analyses were performed and binding relationships between circRNAs and miRNAs were predicted. The hsa_circ_0001766/miR-877-3p/VEGFA axis was selected to further elucidate its role in OSCC.ResultsWe showed that there were 122 differentially expressed (DE) circRNAs. Eight out of 10 selected circRNAs were validated by qRT-PCR. GO and KEGG analyses indicated that the identified DE circRNAs might be involved in the progression of OSCC. Then, after identification by Sanger sequencing and RNase R assay, the upregulated hsa_circ_0001766 was selected to investigate its potential role in OSCC. Bioinformatics analysis showed that hsa_circ_0001766 might act as a competing endogenous RNA (ceRNA) that sponged miR-877-3p to upregulate VEGFA expression. We selected OSCC cell lines SCC9 and SCC25. PCR results showed that the expression of hsa_circ_0001766 and VEGFA was upregulated in SCC9 and SCC25. Subsequently, using western blot, PCR, CCK8, and colony formation assays, we found that knocking down circRNA0001766 inhibited the expression of VEGFA and the proliferation of OSCC cells. Following this, miR-877-3p inhibitor reversed the inhibitory effect of si-hsa_circ_0001766 on expression of VEGFA and proliferation of OSCC cells.ConclusionsIn conclusion, our study revealed the possible role of circRNAs in the pathogenesis of OSCC, and identified the potential role of the hsa_circ_0001766/miR-877-3p/VEGFA axis in OSCC progression.

Project description:BackgroundChronic thromboembolic pulmonary hypertension (CTEPH) is a rare but debilitating and life-threatening complication of acute pulmonary embolism. Circular RNAs (circRNAs), presenting as covalently closed continuous loops, are RNA molecules with covalently joined 3'- and 5'-ends formed by back-splicing events. circRNAs may be significant biological molecules to understand disease mechanisms and to identify biomarkers for disease diagnosis and therapy. The aim of this study was to investigate the potential roles of circRNAs in CTEPH.MethodsTen human blood samples (5 each from CTEPH and control groups) were included in the Agilent circRNA chip. The differentially expressed circRNAs were evaluated using t test, with significance set at a P value of < .05. A functional enrichment analysis for differentially expressed circRNAs was performed using DAVID online tools, and a Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis for target genes of miRNAs was performed using the R package clusterProfiler. Furthermore, miRNAs that interacted with differentially expressed circRNAs were predicted using the miRanda package. mRNAs that had clear biological functions and were regulated by miRNAs were predicted using miRWalk2.0 and then combined into a circRNA-miRNA-mRNA network.ResultsIn total, 351 differentially expressed circRNAs (122 upregulated and 229 downregulated) between CTEPH and control groups were obtained; among these circRNAs, hsa_circ_0002062 and hsa_circ_0022342 might be important because they can regulate 761 (e.g., hsa-miR-942-5p) and 453 (e.g., hsa-miR-940) miRNAs, respectively. Target genes (e.g., cyclin-dependent kinase 6) of hsa-miR-942-5p were mainly enriched in cancer-related pathways, whereas target genes (e.g., CRK-Like Proto-Oncogene, Adaptor Protein) of hsa-miR-940 were enriched in the ErbB signaling pathway. Therefore, these pathways are potentially important in CTEPH.ConclusionsOur findings suggested that hsa_circ_0002062 and hsa_circ_0022342 may be key circRNAs for CTEPH development and that their targeted regulation may be an effective approach for treating CTEPH.

Dataset Information

Circular RNA profile of parathyroid neoplasms: analysis of co-expression networks of circular RNAs and mRNAs.

Publications

Circular RNA profile of parathyroid neoplasms: analysis of co-expression networks of circular RNAs and mRNAs.

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