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

Abstract

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.