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miRNA‐31 increases radiosensitivity through targeting STK40 in colorectal cancer cells
Author(s) -
Zhang Weiwei,
Zhu Yuequan,
Zhou Yuan,
Wang Junjie,
Jiang Ping,
Xue Lixiang
Publication year - 2022
Publication title -
asia‐pacific journal of clinical oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.73
H-Index - 29
eISSN - 1743-7563
pISSN - 1743-7555
DOI - 10.1111/ajco.13602
Subject(s) - radiosensitivity , microrna , colorectal cancer , cancer research , biology , cell culture , gene silencing , cancer , radioresistance , cell , radiation therapy , medicine , gene , genetics
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.