Dataset Information

Construction and Investigation of a lncRNA-Associated ceRNA Regulatory Network in Cholangiocarcinoma.

ABSTRACT: Background/Aims: As a type of malignant tumor commonly found in the bile duct, cholangiocarcinoma (CCA) has a poor prognosis. Long non-coding RNA (lncRNA) has recently drawn increasing attention because it functions as a competing endogenous RNA (ceRNA) to hinder miRNA functions that participate in posttranscriptional regulatory networks in tumors. Therefore, to investigate the mechanisms of CCA carcinogenesis and to enhance treatment efficiency, the expression profiles, including lncRNA, miRNA, and mRNA data, were comprehensively integrated and analyzed in this study. Methods: A comprehensive comparison was performed on the RNA-sequencing and miRNA profiles data of 36 CCA samples and 9 normal samples from The Cancer Genome Atlas (TCGA) database. Then, a dysregulated lncRNA-related ceRNA network was established by using four public databases. Results: In summary, 1,410 lncRNAs, 64 miRNAs, and 3,494 mRNAs appeared as genes that were aberrantly expressed in CCA. Then, a dysregulated ceRNA network related to the lncRNAs was constructed. The network included 116 lncRNAs, 13 miRNAs and 60 mRNAs specific to CCA. The survival analysis showed that, among them, 26 lncRNAs, 3 miRNAs, and 13 mRNAs were prognostic biomarkers for patients with CCA. Finally, three mRNAs were selected for validation of their expression levels in the Gene Expression Omnibus (GEO) database. The results indicated that the expression of those genes was highly consistent between the TCGA and GEO databases. Conclusions: The findings in this study provide a better understanding of the ceRNA network involved in CCA biology and lay a solid foundation for improving CCA diagnosis and prognosis.

SUBMITTER: Long J

PROVIDER: S-EPMC6696726 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Construction and Investigation of a lncRNA-Associated ceRNA Regulatory Network in Cholangiocarcinoma.

Long Junyu J Xiong Jianping J Bai Yi Y Mao Jinzhu J Lin Jianzhen J Xu Weiyu W Zhang Hui H Chen Shuguang S Zhao Haitao H

Frontiers in oncology 20190809

<b>Background/Aims:</b> As a type of malignant tumor commonly found in the bile duct, cholangiocarcinoma (CCA) has a poor prognosis. Long non-coding RNA (lncRNA) has recently drawn increasing attention because it functions as a competing endogenous RNA (ceRNA) to hinder miRNA functions that participate in posttranscriptional regulatory networks in tumors. Therefore, to investigate the mechanisms of CCA carcinogenesis and to enhance treatment efficiency, the expression profiles, including lncRNA, ...[more]

PMID: 31448221

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Project description:Purpose:Accumulating evidence has indicated that circRNAs are closely involved in tumorigenesis and progression of human cancers. However, the molecular mechanism underlying function of circRNAs in breast cancer has not been thoroughly elucidated. Currently, we aimed to characterize the circRNA-related competing endogenous RNA (ceRNA) regulatory network in breast cancer and to construct prognostic model. Materials and Methods:First, we constructed circRNA expression profiles for paired breast cancer in a Chinese population using a human circRNA microarray. Expression profiles of circRNAs, miRNAs, and mRNAs were retrieved from our circRNA dataset, the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. We applied the limma and edgeR packages to identify differentially expressed RNAs. Weighted gene correlation network analysis (WGCNA) was used to identify critical modules of mRNAs. Next, a ceRNA network was established based on circRNA-miRNA and miRNA-mRNA intersections. Both Cox regression analysis and ROC curve analysis were performed to generate prognostic model. Additionally, we performed Gene Set Enrichment Analysis (GSEA) on prognostic signatures. Results:Total of 59 circRNAs, 98 miRNAs and 3966 mRNAs were identified as differentially expressed RNAs. We first identified 38 miRNA-mRNA pairs and 38 circRNA-miRNA pairs to construct the circRNA-miRNA-mRNA regulatory network and then generated a prognostic model based on 7 signatures (MMD, SLC29A4, CREB5, FOS, ANKRD29, MYOCD, and PIGR), and patients with high-risk scores presented poor prognosis. Several cancer-related pathways were enriched, including the TGF-? pathway, the focal adhesion pathway, and the JAK-STAT signaling pathway, and 20 prognostic ceRNA regulatory networks were subsequently identified. Conclusion:In all, we screened a series of dysregulated circRNAs, miRNAs, and mRNAs, and constructed circRNA-related ceRNA network in breast cancer. Our findings may help to deepen the understanding of circRNA-related regulatory mechanisms. Moreover, we generated a prognostic model that provided new insight into postoperative management for breast cancer.

Project description:The low survival rate associated with serous ovarian carcinoma (SOC) is largely due to the lack of relevant molecular markers for early detection and therapy. Increasing experimental evidence has demonstrated that long noncoding RNAs (lncRNAs) are involved in cancer initiation and development, and a competitive endogenous RNA (ceRNA) hypothesis has been formulated. Therefore, the characterization of new lncRNA and lncRNA-related networks is crucial for early diagnosis and targeted therapy of SOC. Data on lncRNAs, mRNAs, and miRNAs with differential expression in SOC, compared to normal ovarian tissue, were obtained from the Gene Expression Omnibus (GEO) database. Data on lncRNA expression and clinical data in SOC were obtained from The Cancer Genome Atlas (TCGA). lncRNA-miRNA interactions were predicted by the miRBase database. Different online tools, i.e., TargetScan, RNA22, miRmap, microT, miRanda, StarBase, and PicTar, were cooperatively utilized to predict the mRNAs targeted by miRNAs. The plugin of BiNGO in Cytoscape and KOBAS 3.0 were used to conduct the functional and pathway enrichment analyses. The lncRNA, miRNAs, and mRNAs identified to be expressed at statistically significant and different levels between SOC and healthy fallopian tube tissues were further validated using qRT-PCR. A total of 4 lncRNAs (LINC00284, HAGLR, HCAT158, and BLACAT1) and 111 mRNAs were found to be upregulated in SOC tissues compared to normal tissues, based on the GEO database. LINC00284 was found to be highly expressed in SOC, in association with the upregulation of the transcription factor SOX9. The high LINC00284 expression was associated with poor prognosis and proved to be an independent risk factor in patients with SOC, based on TCGA database. The qRT-PCR validation results closely recapitulated the expression profiles and prognostic scores of the aforementioned bioinformatic analyses. The LINC00284-related ceRNA network was found to be associated with SOC carcinogenesis by biofunctional analysis. In conclusion, the LINC00284-related ceRNA network may provide valuable information on the mechanisms of SOC initiation and progression. Importantly, LINC00284 proved to be a new potential prognostic biomarker for SOC.

Dataset Information

Construction and Investigation of a lncRNA-Associated ceRNA Regulatory Network in Cholangiocarcinoma.

Publications

Construction and Investigation of a lncRNA-Associated ceRNA Regulatory Network in Cholangiocarcinoma.

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