miR-770-5p modulates resistance to methotrexate in human colorectal adenocarcinoma cells by downregulating HIPK1.

Colon cancer is one of the most common types of cancer worldwide. Methotrexate (MTX) is a chemotherapy drug used for the treatment of multiple types of cancer, such as colon and breast cancer. To determine the effects of MTX treatment on colorectal adenocarcinoma cell lines, a microRNA (miRNA) microarray was used to detect miRNA expression profiles of HT-29 colorectal adenocarcinoma MTX-resistant cells and their parental cells. The results demonstrated that 641 genes and 43 miRNAs were differentially expressed between HT-29 MTX-sensitive cells and MTX-resistant cells. In addition, 12 miRNAs and their co-expressed genes were highly correlated in MTX treatment, and one of the identified miRNAs, miR-770-5p, was studied in subsequent experiments. Upregulation of miR-770-5p significantly decreased the sensitivity of HT-29 cells to MTX. Using bioinformatics software, homeodomain-interacting protein kinase 1 (HIPK1) was identified to be a putative target gene of miR-770-5p, which was confirmed by a luciferase reporter assay. Downregulation of miR-770-5p target gene HIPK1 significantly decreased the sensitivity of HT-29 cells to MTX. These results suggest that miR-770-5p may be involved in the regulation of colon cancer resistance to MTX by regulating the expression of the target gene HIPK1.