Back to Search
Start Over
Development of novel predictive miRNA/target gene pathways for colorectal cancer distance metastasis to the liver using a bioinformatic approach
- Source :
- PLoS ONE, Vol 14, Iss 2, p e0211968 (2019), PLoS ONE
- Publication Year :
- 2019
- Publisher :
- Public Library of Science (PLoS), 2019.
-
Abstract
- BackgroundLiver metastases are the major cause of colorectal cancer (CRC)-related deaths. However, there is no reliable clinical predictor for CRC progression to liver metastasis. In this study, we investigated possible predictors (miRNAs and biomarkers) for clinical application.MethodologyThe Gene Expression Omnibus (GEO) datasets GSE49355, GSE41258 and GSE81558 for genes and GSE54088 and GSE56350 for miRNAs were used to identify common differentially expressed genes (DEGs) and miRNAs between primary CRC tissues and liver metastases. The identified miRNAs and their targets from the DEGs were verified in datasets comprising gene, miRNA and miRNA exosome profiles of CRC patients with no distant metastases (M0) and distant metastases (M1); the interaction networks and pathways were also mapped.ResultsThere were 49 upregulated and 13 downregulated DEGs and 16 downregulated and 14 upregulated miRNAs; between the DEGs and miRNA targets, there were five upregulated and four downregulated genes. MiR-20a was strongly correlated with the status of liver metastasis. MiR-20a, miR499a, and miR-576-5p were highly correlated with the metastatic outcomes. MiR-20a was significantly highly expressed in the M1 group. In an analysis of the miRNA target genes, we found that CDH2, KNG1, and MMP2 were correlated with CRC metastasis. We demonstrated a new possible pathway for CRC metastasis: miR-576-5p/F9, miR20a/MMP2, CTSK, MMP3, and miR449a/P2RY14. The regulation of IGF transport and uptake by IGFBPs, extracellular matrix organization, signal transduction and the immune system were the enriched pathways.ConclusionThis model can predict CRC to liver metastases and the pathways involved, which can be clinically applicable.
- Subjects :
- 0301 basic medicine
MMP2
Microarrays
Exosomes
Biochemistry
Metastasis
0302 clinical medicine
Basic Cancer Research
Databases, Genetic
Medicine and Health Sciences
Gene Regulatory Networks
Oligonucleotide Array Sequence Analysis
Regulation of gene expression
Multidisciplinary
Liver Neoplasms
Cadherins
Extracellular Matrix
Nucleic acids
Gene Expression Regulation, Neoplastic
Bioassays and Physiological Analysis
Oncology
030220 oncology & carcinogenesis
Matrix Metalloproteinase 2
Medicine
Cellular Structures and Organelles
Anatomy
Colorectal Neoplasms
Research Article
Extracellular matrix organization
Colon
Science
Biology
Research and Analysis Methods
Exosome
03 medical and health sciences
Antigens, CD
microRNA
Genetics
Biomarkers, Tumor
medicine
Humans
Vesicles
Non-coding RNA
Colorectal Cancer
Natural antisense transcripts
Biology and life sciences
Models, Genetic
Kininogens
Gene Expression Profiling
Cancers and Neoplasms
Computational Biology
Cell Biology
medicine.disease
Microvesicles
Gene regulation
Gastrointestinal Tract
Gene expression profiling
MicroRNAs
030104 developmental biology
Cancer research
RNA
Gene expression
Digestive System
Subjects
Details
- Language :
- English
- ISSN :
- 19326203
- Volume :
- 14
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- PLoS ONE
- Accession number :
- edsair.doi.dedup.....9c9a48b66895f71f1c2ac286abce409d