Circ_0007580 knockdown strengthens the radiosensitivity of non-small cell lung cancer via the miR-598-dependent regulation of THBS2.

backgroundRadioresistance is a common cause of treatment failure in many cancers, including non-small cell lung cancer (NSCLC). Circular RNA (circRNA) has been shown to be involved in the radiosensitivity of many cancers. However, the role and mechanism of circ_0007580 in the radiosensitivity of NSCLC remain unclear.

methodsThe expression levels of circ_0007580, miR-598 and thrombospondin 2 (THBS2) were estimated by quantitative real-time PCR. The radiosensitivity of cells was measured using colony formation assay. Cell proliferation and apoptosis were assessed by performing cell counting kit 8 assay, colony formation assay, flow cytometry, and by detecting caspase-3 and caspase-9 activities. Protein expression was determined using western blot analysis.

resultsOur data showed that circ_0007580 was highly expressed and miR-598 was lowly expressed in radioresistant NSCLC tissues. Functional experiments suggested that circ_0007580 silencing could improve the radiosensitivity of cells by suppressing cell proliferation and increasing apoptosis. MiR-598 was confirmed to be a target of circ_0007580, and its inhibitor could reverse the regulation of circ_0007580 on the radiosensitivity of NSCLC cells. MiR-598 was found to target THBS2. The suppressive effect of miR-598 on the radiosensitivity of cells could be reversed by THBS2 overexpression. Additionally, circ_0007580 could sponge miR-598 to regulate THBS2. In vivo experiments showed that knockdown of circ_0007580 enhanced the radiosensitivity of NSCLC tumors.

conclusionsOur results revealed that circ_0007580 might be a target for improving the radiosensitivity of NSCLC, which was mainly achieved by regulating the miR-598/THBS2 axis.