Identification of novel survival-related lncRNA-miRNA-mRNA competing endogenous RNA network associated with immune infiltration in colorectal cancer.

Increasing studies have reported that long noncoding RNAs (lncRNAs) play critical roles in the initiation and progression of carcinogenesis. However, the underlying regulatory mechanisms of lncRNA-related competing endogenous RNA (ceRNA) network in colorectal cancer (CRC) are not fully understood. In the present study, we systematically analyzed the expression levels and prognostic values of dysregulated microRNAs (miRNAs) in human CRC to identify novel survival-related lncRNA-miRNA-mRNA ceRNA regulatory network. As a result, 28 dysregulated miRNAs were obtained, and hsa-miR-195-5p was identified as a key oncogene in human CRC based on analyses of expression levels and prognostic values. By means of stepwise prediction and validation, two upstream lncRNAs (NEAT1, XIST) and eight downstream mRNAs (ACOX1, CYP26B1, IRF4, ITPR1, LITAF, PHLPP2, RECK, and TPM2) were identified as key genes that interact with hsa-miR-195-5p. A ceRNA regulatory network consisted of these key genes was constructed, and Gene Set Enrichment Analysis (GSEA) indicated the possible association of key mRNAs with CRC onset and progression. Importantly, immune infiltration analysis revealed that the ceRNA network was remarkably associated with infiltration abundance of multiple immune cells and expression levels of immune checkpoints. These findings indicate that NEAT1 and XIST are potential prognostic factors that affect CRC onset and progression by targeting miR-195-5p.