Department of Thoracic Radiation Oncology, Harbin Medical University Cancer Hospital, Harbin, China.
Department of Radiation Oncology, Xiang'an Hospital of Xiamen University, Xiamen, China.
Cancer Lett. 2022 Feb 1;526:1-11. doi: 10.1016/j.canlet.2021.11.009. Epub 2021 Nov 18.
The long noncoding RNA CBR3-AS1 has important functions in various cancers. However, the biological functions of CBR3-AS1 in non-small cell lung cancer (NSCLC) remain unclear. This study aimed to investigate the roles and molecular mechanisms of CBR3-AS1 in NSCLC tumorigenesis and radiosensitivity. Here, we demonstrate CBR3-AS1 overexpression in NSCLC tissue compared with adjacent normal tissue. CBR3-AS1 downregulation reduced proliferation, invasion, and migration; inhibited cell cycle progression; and promoted apoptosis of NSCLC cells. CBR3-AS1 also promoted tumor growth in vivo. CBR3-AS1 may regulate the expression and functions of the miR-409-3p target gene SOD1. CBR3-AS1 expression was negatively correlated with radiosensitivity. CBR3-AS1 downregulation decreased post-irradiation SOD1 expression, increased γH2AX formation, raised levels of reactive oxygen species, and promoted apoptosis. Our results suggest that CBR3-AS1 functions as an oncogene through the CBR3-AS1/miR-409-3p/SOD1 pathway, and may represent a new therapeutic target, especially to regulate radiosensitivity in NSCLC.
长链非编码 RNA CBR3-AS1 在各种癌症中具有重要功能。然而，CBR3-AS1 在非小细胞肺癌（NSCLC）中的生物学功能仍不清楚。本研究旨在探讨 CBR3-AS1 在 NSCLC 发生和放射敏感性中的作用和分子机制。在这里，我们证明了与相邻正常组织相比，CBR3-AS1 在 NSCLC 组织中表达上调。CBR3-AS1 的下调减少了 NSCLC 细胞的增殖、侵袭和迁移；抑制细胞周期进程；并促进细胞凋亡。CBR3-AS1 还促进了体内肿瘤的生长。CBR3-AS1 可能调节 miR-409-3p 靶基因 SOD1 的表达和功能。CBR3-AS1 的表达与放射敏感性呈负相关。CBR3-AS1 的下调降低了照射后 SOD1 的表达，增加了 γH2AX 的形成，提高了活性氧水平，并促进了细胞凋亡。我们的研究结果表明，CBR3-AS1 通过 CBR3-AS1/miR-409-3p/SOD1 途径发挥癌基因作用，可能代表一种新的治疗靶点，特别是调节 NSCLC 的放射敏感性。
