Integrated regulatory mechanisms of miRNAs and targeted genes involved in colorectal cancer.

PURPOSE

CRC (Colorectal cancer) is a lethal cancer for death worldwide and the underlying pathological mechanisms for CRC progression remain unclear. We aimed to explore the regulatory mechanism of CRC and provide novel biomarkers for CRC screening.

METHODS

Downloading from GEO (Gene Expression Omnibus) database, Microarray data GSE44861 were consisted of 111 colon tissues samples including 55 from adjacent noncancerous tissues and 56 from tumors tissues. After data pre-processing, up- and down regulated DEGs (differentially expressed genes) were identified using Bayes moderated t-test. Then DIVAD (Database for Annotation, Visualization and Integrated Discovery) was recruited to perform functional analysis for DEGs. Thereafter, PPI (protein-protein interaction) network was constructed by mapping DEGs into STRING (Search Tool for the Retrieval of Interacting Genes) database. Further, PPI modules were constructed and the protein domains of DEGs in the modules were analyzed. Moreover, miRNA regulatory network was established through GSEA (gene set enrichment analysis) method.

RESULTS

In summary, 96 up- and 212 down-regulated DEGs were identified. Totally, ten DEGs with high degrees in the constructed PPI network were selected, in which COLL1A1, PTGS2 and ASPN were also identified as crucial genes in PPI modules. Furthermore, COLL1A1 was predicted to be targeted by miR-29, while PTGS2 and ASPN were both predicted to be regulated by miR-101 and miR-26.

CONCLUSION

COL11A1 might involve in the progression of CRC via being targeted by miR-29, whereas PTGS2 and ASPN were both regulated by miR-101 and miR-26. Moreover, ASPN may be supposed as a novel biomarker for CRC detection and prevention.