Radiotherapy resistance is one of the main causes for treatment failure in
colorectal cancer (CRC), and it is associated with the deregulation of certain
microRNAs. In this study, we constructed the
microRNA-
mRNA network consisting of 2275
microRNAs and 7045 target genes, collected the known
microRNAs related to CRC-radiosensitivity (CRCR) (n=18) as the seed nodes, and applied the algorithm of random walk with restart (RWR) to the network to identify novel CRCR-related
microRNAs (n=263). In functional analysis, 263 novel
microRNAs shared a high proportion of the same biological processes and pathways with the known
microRNAs. In topological analysis of the sub-network of the 263
microRNAs and their targets, hsa-mir-506-3p and hsa-mir-140-5p were identified as network hub nodes. In plasma, radiosensitive patients had a higher expression level of hsa-mir-506-3p and hsa-mir-140-5p than radioresistant patients. In experimental validation, both hsa-mir-506-3p and hsa-mir-140-5p over-expression could obviously decrease the cell proliferation, survival rate and colonality in CRC cells after radiation. In conclusion, this study combined the novel network-based method with experimental validation, and identified two novel radiosensitive
biomarkers of hsa-mir-506-3p and hsa-mir-140-5p in CRC.