Comprehensive Analysis of miRNA-Mediated Regulatory Network and Identification of Prognosis Biomarkers in Rectal Cancer.

Abstract

Rectal cancer is a malignant tumor with poor prognosis. Identification of prognostic biomarkers is needed to improve overall survival of rectal cancer patients. Here, we firstly identified miR-20a-5p significantly classifying high-risk group and low-risk group of rectal cancer patients. We also found that several known miRNAs miR-142-5p, miR-486-5p, miR-490-3p and miR-133a-3p played important roles in rectal cancer. Secondly, we constructed and analyzed a rectal cancer-related miRNA-mRNA network. A rectal cancer-related functional module was identified from the miRNA-mRNA network. Survival analysis demonstrated great prognosis capacity of the module to distinguish rectal cancer patients. Thirdly, a rectal cancer-related miRNA-lncRNA network was constructed, which followed power law distribution. Hub miRNAs and lncRNAs of the network were suggested to show significant prognosis ability and be enriched in cancer-related pathways. Fourthly, we constructed a rectal cancer-related ceRNA network and detected several typical lncRNA-miRNA-mRNA crosstalk, such as HAND2-AS1, HAND2 and miR-20a-5p crosstalk and MBNL1-AS1, miR-429 and LONRF2 crosstalk, which were validated to function in improving overall survival of rectal cancer patients. Finally, we identified the regulatory feedback that was constituted by transcriptional factors and lncRNAs, including MEIS1, MEIS2 and multiple lncRNAs. We also demonstrated that these lncRNAs were high related to immune cell infiltration. All these results can help us to uncover the molecular mechanism and provide new light on miRNA-mediated gene crosstalks in rectal cancer.