Dataset Information

Comprehensive circular RNA expression profiling constructs a ceRNA network and identifies hsa_circ_0000673 as a novel oncogene in distal cholangiocarcinoma.

ABSTRACT: Circular RNAs (circRNAs) play an important role in cholangiocarcinoma (CCA) development; however, the expression and functions of circRNAs in distal CCA (dCCA) remain unknown. Herein, we explored the expression profile of circRNAs in six paired dCCA tumor and adjacent normal tissue samples using microarray. A total of 171 differentially expressed (DE) circRNAs were identified in dCCA tissues. Host genes of DE circRNAs were enriched in the cellular cytoskeleton and adheren junction. Bioinformatics analyses were used to establish a circRNA-microRNA-mRNA network for dCCA. Protein-protein interaction networks were constructed, and five hub genes were associated with the regulation of the cell cycle based on gene set enrichment analyses. Five DE circRNAs were validated with qRT-PCR in 40 pairs of dCCA tissues, and hsa_circ_0000673 showed promising diagnostic performance in distinguishing dCCA from normal tissues (AUC = 0.85, p < 0.01). Overexpression of hsa_circ_0000673 was associated with tumor invasion (p = 0.001), poor differentiation (p = 0.041), and residual tumor (p = 0.044). In vitro experiments indicated that inhibition of hsa_circ_0000673 suppressed the proliferation, migration, and invasion of CCA cells. This research provided a landscape of dysregulated circRNAs in dCCA and identified hsa_circ_0000673 as a potential biomarker and therapeutic target for dCCA.

SUBMITTER: Zhao X

PROVIDER: S-EPMC7746367 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Comprehensive circular RNA expression profiling constructs a ceRNA network and identifies hsa_circ_0000673 as a novel oncogene in distal cholangiocarcinoma.

Zhao Xin X Zhang Xinxue X Zhang Zhigang Z Liu Zhe Z Zhu Jiqiao J Lyu Shaocheng S Li Lixin L Lang Ren R He Qiang Q

Aging 20201118 22

Circular RNAs (circRNAs) play an important role in cholangiocarcinoma (CCA) development; however, the expression and functions of circRNAs in distal CCA (dCCA) remain unknown. Herein, we explored the expression profile of circRNAs in six paired dCCA tumor and adjacent normal tissue samples using microarray. A total of 171 differentially expressed (DE) circRNAs were identified in dCCA tissues. Host genes of DE circRNAs were enriched in the cellular cytoskeleton and adheren junction. Bioinformatic ...[more]

PMID: 33221765

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Project description:Osteosarcoma is a highly malignant bone cancer which primarily occurs in children and young adults. Increasing evidence indicates that long noncoding RNAs (lncRNAs), which function as competing endogenous RNAs (ceRNAs) that sponge microRNAs (miRNAs) and messenger RNAs (mRNAs), play a pivotal role in the pathogenesis and progression of cancers. The regulatory mechanisms of lncRNA-mediated ceRNAs in osteosarcoma have not been fully elucidated. In this study, we identified differentially expressed lncRNAs, miRNAs, and mRNAs in osteosarcoma based on RNA microarray profiles in the Gene Expression Omnibus (GEO) database. A ceRNA network was constructed utilizing bioinformatic tools. Kaplan-Meier survival analysis showed that lncR-C3orf35 and HMGB1 were associated with poor prognosis of osteosarcoma patients. Furthermore, results of Gene Set Enrichment Analysis (GSEA) suggested that lncR-C3orf35 may be involved in cellular invasion, the Toll-like receptor signaling pathway, and immune cell infiltration in the tumor microenvironment. Further analysis showed that patients with osteosarcoma metastasis expressed higher levels of lncR-C3orf35 and HMGB1 compared to metastasis-free patients. Moreover, the metastasis-free survival rate of the high lncR-C3orf35/HMGB1 expression group was significantly lower than that of the low expression group. The ESTIMATE algorithm was used to calculate the immune score and stromal scores for each sample. High lncR-C3orf35 and HMGB1 levels were correlated with low immune scores. ImmuCellAI analysis revealed that a low proportion of macrophage infiltration was associated with high lncR-C3orf35 and HMGB1 expression. The differential expression of lncR-C3orf35, miR-142-3p, and HMGB1 was further verified by quantitative real-time PCR. This study indicates that lncR-C3orf35 could be considered as a novel potential biomarker and therapeutic target of osteosarcoma, which may contribute to a better understanding of ceRNA regulatory mechanisms.

Dataset Information

Comprehensive circular RNA expression profiling constructs a ceRNA network and identifies hsa_circ_0000673 as a novel oncogene in distal cholangiocarcinoma.

Publications

Comprehensive circular RNA expression profiling constructs a ceRNA network and identifies hsa_circ_0000673 as a novel oncogene in distal cholangiocarcinoma.

Similar Datasets

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