Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
Department of Oncology Medicine, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
J Cell Physiol. 2021 Jan;236(1):79-92. doi: 10.1002/jcp.29481. Epub 2020 Aug 16.
Circular RNAs (circRNAs) have been associated with lung cancer (LC), one of the most common cancers, but the underlying molecular mechanisms of the specific correlation with LC carcinogenesis remain unveiled. Quantitative real-time polymerase chain reaction was applied to examine the level of circZNF609. LC cells were transfected with silenced circZNF609 by siRNAs, and cell proliferation, migration, and apoptosis were evaluated to reflect the influences of circZNF609 knockdown in LC. Biotin-coupled circRNA capture, FISH and luciferase reporter assays were performed to study the relationship between circZNF609 and miR-142-3p. In current work, it was discovered that circZNF609 functioned as an onco-circRNA, which exhibited high expression as well as facilitated the proliferation and migration in LC cells. Next, we discovered that FUS RNA-binding protein, which could bind to the ZNF609 pre-mRNA, induced circZNF609 formation, and increased circZNF609 expression in LC. Furthermore, circZNF609 was verified to sponge and sequester miR-142-3p; circZNF609 enhanced LC cell proliferative and migrative ability via targeting miR-142-3p. Finally, G protein subunit beta 2 (GNB2) was figured out to involve in circZNF609/miR-142-3p axis-induced LC development. Conclusively, the results indicated that FUS-induced circZNF609 exerts promotional effects on LC cell proliferation and migration through modulation of the miR-142-3p/GNB2 axis, which could offer new insight for understanding LC.
环状 RNA（circRNAs）与肺癌（LC）有关，肺癌是最常见的癌症之一，但与 LC 致癌作用相关的确切分子机制仍未被揭示。采用定量实时聚合酶链反应检测 circZNF609 的水平。用 siRNA 转染沉默 circZNF609 的 LC 细胞，并评估细胞增殖、迁移和凋亡，以反映 circZNF609 敲低对 LC 的影响。进行生物素偶联的 circRNA 捕获、FISH 和荧光素酶报告基因检测，以研究 circZNF609 与 miR-142-3p 之间的关系。在本工作中，发现 circZNF609 作为致癌 circRNA，其表达水平较高，促进 LC 细胞的增殖和迁移。接下来，我们发现可以与 ZNF609 前体 RNA 结合的 FUS RNA 结合蛋白诱导 circZNF609 形成，并增加 LC 中的 circZNF609 表达。此外，circZNF609 被证实可以海绵吸附并隔离 miR-142-3p；circZNF609 通过靶向 miR-142-3p 增强 LC 细胞的增殖和迁移能力。最后，确定 G 蛋白亚单位β 2（GNB2）参与 circZNF609/miR-142-3p 轴诱导的 LC 发展。总之，结果表明，FUS 诱导的 circZNF609 通过调节 miR-142-3p/GNB2 轴对 LC 细胞增殖和迁移发挥促进作用，为理解 LC 提供了新的视角。
