miRNA-31 increases radiosensitivity through targeting STK40 in colorectal cancer cells

Abstract

Objective: To propose and verify that miRNA-31 increases the radiosensitivity of colorectal cancer and explore its potential mechanism.

Method: A bioinformatics analysis was performed to confirm that the expression of miRNA-31 was higher in colorectal cancer than in normal colorectal tissue. The expression of miRNA-31 was detected to verify the change in its expression in a radiotherapy-resistant cell line. Methylation was detected to explore the cause of the decrease in miRNA-31 expression. Overexpression or inhibition of miRNA-31 further confirmed the change in its expression in colorectal cancer cell lines. Bioinformatics methods were used to screen the downstream target genes and for experimental verification. A luciferase assay was performed to determine the miRNA-31 binding site in STK40. Overexpression or inhibition of STK40 in colorectal cancer cell lines further confirmed the change in STK40 expression in vitro.

Results: The bioinformatics results showed higher expression of miRNA-31 in tumors than in normal tissue, and miRNA-31 mainly participated in the pathway related to cell replication. Next, we observed the same phenomenon: miRNA-31 was expressed at higher levels in colorectal tumors than in normal colorectal tissue and its expression decreased in radiation-resistant cell lines after radiation, implying that miRNA-31 increased the radiosensitivity of colorectal cancer cell lines. No significant change in upstream methylation was observed. miRNA-31 regulated the radiosensitivity of colorectal cancer cell lines by inhibiting STK40. Notably, miRNA-31 played a role by binding to the 3' untranslated region of SK40. STK40 negatively regulated the radiosensitivity of colorectal cancer cells.

Conclusions: miRNA-31 increases the radiosensitivity of colorectal cancer cells by targeting STK40; miRNA-31 and STK40 are expected to become potential biomarkers for increasing the sensitivity of tumor radiotherapy in clinical treatment.

Keywords: STK40; colorectal cancer; miRNA-31; potential biomarker; radiosensitivity.