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Published on: March 30, 2019
Identification of a potentially functional circRNA-miRNA-mRNA ceRNA regulatory network in bladder cancer by analysis
Lei Du1, Xin Wang1, Yuewei Yin1
1Department of Urology, The Second Hospital of Hebei Medical University, Shijiazhuang, China.
Background:
Circular RNAs (circRNAs) have received increasing attention in cancer development. However, a substantial number of circRNAs still require characterization. The purpose of this study is to uncover novel circRNAs and their molecular mechanism in bladder cancer (BCa).
Methods:
A combinative strategy of extensive data mining and computational biology was employed to identify BCa-related circRNAs and explore their potential mechanisms of action.
Results:
Three differentially expressed circRNAs (has_circ_0023642, has_circ_0047322, has_circ_0041151) were obtained from the microarray dataset (GSE92675). Four miRNAs (miR-616, miR-515-5p, miR-647, miR-1178) with potential binding sites with these three circRNAs were identified. Pathway analysis demonstrated that all four miRNAs were closely associated with some cancer-related pathways. Survival analysis indicated that these miRNAs might potentially play a role in tumor-suppressive functions in BCa. Subsequently, 181 overlapping genes were identified from 472 up-regulated genes in BCa (TCGA database), and 10,017 predicted target genes of the four miRNAs obtained. A circRNA-miRNA-mRNA network was constructed on the identified three circRNAs, four miRNAs, and 181 overlapping genes. Besides, six hub genes (CENPA, HIST1H2BJ, HIST1H2BO, HIST1H3H, HIST1H3B, HIST1H3F) were identified from establishing a protein-protein interaction (PPI) network on the same overlapping genes. Furthermore, a circRNA-miRNA-hub gene sub-network was built to delineate the links among the differential circRNAs, miRNA, and hub genes.
Conclusions:
Our study provided significant insights into the molecular mechanisms that regulate the progression of BCa from the circRNA-miRNA-mRNA network view.
Insights
This study identifies novel circular RNAs (circRNAs) and their molecular mechanisms in bladder cancer (BCa). A circRNA-miRNA-mRNA network reveals potential tumor-suppressive functions and key hub genes in BCa progression.
Area of Science:
- Oncology
- Molecular Biology
- Bioinformatics
Background:
- Circular RNAs (circRNAs) are increasingly implicated in cancer development.
- Many circRNAs remain uncharacterized, necessitating further investigation into their roles.
- Bladder cancer (BCa) presents a significant area for exploring novel circRNA functions.
Purpose of the Study:
- To identify novel circRNAs associated with bladder cancer.
- To elucidate the molecular mechanisms underlying circRNA involvement in BCa.
- To construct a circRNA-miRNA-mRNA regulatory network for BCa.
Main Methods:
- Utilized extensive data mining and computational biology approaches.
- Integrated microarray data (GSE92675) and The Cancer Genome Atlas (TCGA) database.
- Constructed circRNA-miRNA-mRNA and protein-protein interaction (PPI) networks.
Main Results:
- Identified three differentially expressed circRNAs (has_circ_0023642, has_circ_0047322, has_circ_0041151) and four potential target miRNAs (miR-616, miR-515-5p, miR-647, miR-1178).
- Pathway and survival analyses suggested tumor-suppressive roles for these miRNAs in BCa.
- Established a comprehensive circRNA-miRNA-mRNA network and identified six hub genes (CENPA, HIST1H2BJ, HIST1H2BO, HIST1H3H, HIST1H3B, HIST1H3F).
Conclusions:
- The study provides significant insights into the molecular mechanisms regulating BCa progression.
- The developed circRNA-miRNA-mRNA network offers a novel perspective on BCa pathogenesis.
- Identified key circRNAs, miRNAs, and hub genes that may serve as potential therapeutic targets or biomarkers for BCa.
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