Unearthing Regulatory Axes of Breast Cancer circRNAs Networks to Find Novel Targets and Fathom Pivotal Mechanisms
| Autor: | Mahdieh Salimi, Farzaneh Afzali |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Systems biology
Breast Neoplasms Health Informatics RNA-binding protein Computational biology Biology General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Databases Genetic microRNA Humans Gene Regulatory Networks Triple negative Oligonucleotide Array Sequence Analysis 030304 developmental biology String database 0303 health sciences Sequence Analysis RNA Competing endogenous RNA Microarray analysis techniques Gene Expression Profiling 030302 biochemistry & molecular biology Computational Biology RNA-Binding Proteins RNA Circular Luminal a Computer Science Applications Gene Expression Regulation Neoplastic MicroRNAs Phenobarbital Ppi network Disease Progression Female |
| Zdroj: | Interdisciplinary Sciences: Computational Life Sciences. 11:711-722 |
| ISSN: | 1867-1462 1913-2751 |
| Popis: | Circular RNAs (circRNAs) along other complementary regulatory elements in ceRNAs networks possess valuable characteristics for both diagnosis and treatment of several human cancers including breast cancer (BC). In this study, we combined several systems biology tools and approaches to identify influential BC circRNAs, RNA binding proteins (RBPs), miRNAs, and related mRNAs to study and decipher the BC triggering biological processes and pathways.Rooting from the identified total of 25 co-differentially expressed circRNAs (DECs) between triple negative (TN) and luminal A subtypes of BC from microarray analysis, five hub DECs (hsa_circ_0003227, hsa_circ_0001955, hsa_circ_0020080, hsa_circ_0001666, and hsa_circ_0065173) and top eleven RBPs (AGO1, AGO2, EIF4A3, FMRP, HuR (ELAVL1), IGF2BP1, IGF2BP2, IGF2BP3, EWSR1, FUS, and PTB) were explored to form the upper stream regulatory elements. All the hub circRNAs were regarded as super sponge having multiple miRNA response elements (MREs) for numerous miRNAs. Then four leading miRNAs (hsa-miR-149, hsa-miR-182, hsa-miR-383, and hsa-miR-873) accountable for BC progression were also introduced from merging several ceRNAs networks. The predicted 7- and 8-mer MREs matches between hub circRNAs and leading miRNAs ensured their enduring regulatory capability. The mined downstream mRNAs of the circRNAs-miRNAs network then were presented to STRING database to form the PPI network and deciphering the issue from another point of view. The BC interconnected enriched pathways and processes guarantee the merits of the ceRNAs networks’ members as targetable therapeutic elements.This study suggested extensive panels of novel covering therapeutic targets that are in charge of BC progression in every aspect, hence their impressive role cannot be excluded and needs deeper empirical laboratory designs. |
| Databáze: | OpenAIRE |
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