Long Non-coding RNA CBR3-AS1 Mediates Tumorigenesis and Radiosensitivity of Non-small Cell Lung Cancer through Redox and DNA Repair by CBR3-AS1 /miR-409-3p/SOD1 Axis

Abstract Background: Long noncoding RNA (lncRNA) CBR3-AS1 has important functions in various cancers. However, the biological functions of CBR3-AS1 in non-small lung cancer (NSCLC) remains unclear. This study aimed to investigated the roles and molecular mechanisms of lncRNA CBR3-AS1 in NSCLC tumorigenesis and radiosensitivity. Methods: The association of CBR3-AS1 expression with the clinicopathological features and prognosis of NSCLC was studied based on The Cancer Genome Atlas database and verified in tumor and adjacent normal tissues of 48 NSCLC patients. The effect of CBR3-AS1 knockdown or overexpression on proliferation, apoptosis, migration, and invasion of NSCLC cells were studied through CCK-8, flow cytometry, and transwell assays, and tumorigenesis experiments in nude mice. The interactions of CBR3-AS1, miR-409-3p, and SOD1 were investigated using double luciferase reporter gene. The effect of CBR3-AS1 on NSCLC radiosensitivity was verified using clone formation assay and the single-click multi-target mathematical model. Changes in γH2AX level and reactive oxygen species (ROS) levels were detected using immunofluorescence and flow cytometry in NSCLC cells after irradiation.Results: CBR3-AS1 expression in NSCLC tissue was increased significantly compared with that of surrounding normal tissue. Cell function experiments verified that CBR3-AS1 downregulation could reduce proliferation, invasion, and migration of NSCLC cells and inhibit cell cycle progression and promote apoptosis. The tumorigenesis experiment in nude mice showed that CBR3-AS1 promoted tumor growth. CBR3-AS1 could regulate the expression and functions of the target gene SOD1 of miR-409-3p. High CBR3-AS1 expression in NSCLC was negatively correlated with radiosensitivity. CBR3-AS1 downregulation in NSCLC may depress the expression of SOD1 after irradiation, promote the formation of γH2AX, increase levels of ROS, and increase apoptosis.Conclusions: CBR3-AS1 is highly expressed in NSCLC, and play oncogene function through the CBR3-AS1/miR-409-3p/SOD1 pathway. Downregulation of CBR3-AS1 led to enhanced radiosensitivity, thus providing a new therapeutic target for NSCLC.