The aim of the present study was to identify potential biomarkers associated with colorectal cancer (CRC). The GSE32323 and GSE53592 mRNA and microRNA (miRNA) expression profiles were selected from the Gene Expression Omnibus database. The differentially expressed genes (DEGs) and differentially expressed miRNAs (DEMs) in CRC tissue samples compared with surrounding control tissue samples (DEGs‑CC), and DEGs in cells treated with 5‑aza‑2'‑deoxycitidine compared with untreated cells (DEGs‑TC) were identified with the Limma package. The Database for Annotation, Visualization and Integrated Discovery was used to conduct the functional and pathways enrichment analysis. Differential co‑regulation networks were constructed using the DCGL package of R. The targets of DEMs were identified using TargetScan. The overlaps between DEGs and the targets were selected. The miRNA‑gene regulatory network of the overlaps was established. There were 145DEMs, and 1,284DEGs in DEGs‑CC, and 101 DEGs in DEGs‑TC. DEGs‑CC were enriched in 196 Gene Ontology (GO) terms and 23Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. DEGs‑TC were enriched in 46GO terms and two KEGG pathways. A differential co‑regulation network of the DEGs and a miRNA‑gene regulatory network between DEMs and overlapped DEGs were respectively constructed. miR‑124‑3p, miR‑145‑5p and miR‑320a may be critical in CRC, and serum/glucocorticoid regulated kinase 1 and SRY‑box9 may be potential biomarkers for CRC tumor progression.