Department of Respiration, Jining No.1 People's Hospital, Jining City, China.
Department of Respiration, Jining No.1 People's Hospital, Jining City, China
Biosci Rep. 2019 Jun 4;39(6). doi: 10.1042/BSR20182433. Print 2019 Jun 28.
Circular RNAs (circRNAs), a group of non-coding RNAs, play an important role in cancer biology, and in the present study, we aimed to clarify the expression profiles and biological functions of circRNA circVANGL1 in non-small cell lung cancer (NSCLC). The results showed that circVANGL1 was overexpressed in human NSCLC tissues and cell lines. circVANGL1 expression was closely associated with tumor size, TNM stage and overall survival of NSCLC patients. Further loss-of-function analysis revealed that knockdown of circVANGL1 inhibited proliferation and induced apoptosis in NSCLC cell lines. The migration and invasion of NSCLC cells were also suppressed by circVANGL1 knockdown. In addition, we predicted that circVANGL1 might serve as a competing endogenous RNA (ceRNA), becoming a sink for miR-195, thereby modulating the expression of Bcl-2 in NSCLC cells. Rescue experiments demonstrated that miR-195 inhibitor abrogated the beneficial role of circVANGL1 knockdown in NSCLC cells. Taken together, we conclude that circVANGL1 functions as an oncogene to promote NSCLC progression partly through miR-195/Bcl-2 axis, which might be a novel therapeutic target for NSCLC patients.
环状 RNA（circRNAs）是一组非编码 RNA，在癌症生物学中发挥着重要作用。在本研究中，我们旨在阐明环状 RNA circVANGL1 在非小细胞肺癌（NSCLC）中的表达谱和生物学功能。结果表明，circVANGL1 在人 NSCLC 组织和细胞系中过表达。circVANGL1 的表达与 NSCLC 患者的肿瘤大小、TNM 分期和总生存期密切相关。进一步的功能丧失分析表明，circVANGL1 的敲低抑制了 NSCLC 细胞系的增殖并诱导了细胞凋亡。circVANGL1 的敲低还抑制了 NSCLC 细胞的迁移和侵袭。此外，我们预测 circVANGL1 可能作为竞争性内源性 RNA（ceRNA），成为 miR-195 的吸收物，从而调节 NSCLC 细胞中 Bcl-2 的表达。挽救实验表明，miR-195 抑制剂消除了 circVANGL1 敲低对 NSCLC 细胞的有益作用。总之，我们的结论是 circVANGL1 作为一种癌基因促进 NSCLC 的进展，部分通过 miR-195/Bcl-2 轴，这可能是 NSCLC 患者的一种新的治疗靶点。
