miR-222 enhances radiosensitivity of cancer cells by inhibiting the expression of CD47.

Radiotherapy is one of the most common and effective treatments for localized cancer. However, radiotherapy kills tumor cells while causing damage to surrounding normal cells. Enhancing the radiation sensitivity of tumor cells and reducing the radiation damage to normal cells is a difficult problem. Here, we find that the expression of a human microRNA (miRNA), hsa-miR-222, is upregulated in response to ionizing radiation. TargetScan analysis shows that the 3' UTR of CD47 is potentially targeted by miR-222. This prediction was validated by luciferase reporter and mutation assays. It was demonstrated that miR-222 negatively regulates CD47 expression at mRNA and protein levels, and overexpression of the miR-222 enhances cancer cell radiosensitivity by the CD47-pERK pathway in cancer cells. Our findings enrich the complex relationship between miRNA and CD47 in irradiation stress and shed light on the potential of miRNAs both for direct cancer therapeutics and as tools to sensitize tumor cells to radiotherapy. IJCEP