Department of Respiratory and Critical Care Medicine, Wuhan Third Hospital & Tongren Hospital of Wuhan University, Wuhan, Hubei, China.
Bioengineered. 2022 May;13(5):12067-12087. doi: 10.1080/21655979.2022.2070580.
Circular RNAs (circRNAs) play significant roles in the tumorigenesis and progression of various cancers, including lung adenocarcinoma (LAC). However, their underlying biological functions in LAC remain unclear. Here, we investigated the tumor suppressor role of the newly identified circRNA, circ_0129047, in LAC tumorigenesis and progression. The expression levels of circ_0129047, microRNA (miR)-1206, and bone morphogenetic protein receptor type 2 (BMPR2) mRNA in LAC cells and tissues were monitored using reverse transcription-quantitative polymerase chain reaction. Dual-luciferase reporter, RNA immunoprecipitation, and RNA pull-down assays were used to confirm the targeting relationships among circ_0129047, miR-1206, and BMPR2 mRNA. Functional experiments for A549 and PC9 cells were performed using cell counting kit-8, bromodeoxyuridine enzyme-linked immunosorbent, caspase-3 activity, cell adhesion, wound healing, and transwell assays. Circ_0129047 expression levels were reduced in LAC cells and tissues. Mechanistically, we discovered that circ_0129047 could sponge miR-1206, and miR-1206 could directly target BMPR2. In addition, circ_0129047 or BMPR2 knockdown facilitated the viability, proliferation, adhesion, migration, and invasion, while inhibiting the apoptosis of LAC cells. Furthermore, the inhibitory effects of circ_0129047 or BMPR2 overexpression on the malignant phenotype of LAC cells could be reversed by the overexpression of miR-1206. In conclusion, circ _0129047 was found to play a tumor suppressive role in LAC progression; it upregulated BMPR2 expression to inhibit LAC progression by sponging miR-1206. non-small cell lung cancer (NSCLC); small cell lung cancer (SCLC); lung adenocarcinoma (LAC); Circular RNA (circRNA); MicroRNA (miRNA); bone morphogenetic protein (BMP); squamous cell lung cancer (SCC); RNA immunoprecipitation (RIP).
环状 RNA（circRNAs）在多种癌症的发生和发展中发挥着重要作用，包括肺腺癌（LAC）。然而，它们在 LAC 中的潜在生物学功能尚不清楚。在这里，我们研究了新鉴定的环状 RNA circ_0129047 在 LAC 肿瘤发生和进展中的肿瘤抑制作用。使用逆转录定量聚合酶链反应监测 LAC 细胞和组织中 circ_0129047、microRNA（miR）-1206 和骨形态发生蛋白受体 2（BMPR2）mRNA 的表达水平。双荧光素酶报告、RNA 免疫沉淀和 RNA 下拉实验用于验证 circ_0129047、miR-1206 和 BMPR2 mRNA 之间的靶向关系。使用细胞计数试剂盒-8、溴脱氧尿苷酶酶联免疫吸附、半胱天冬酶-3 活性、细胞黏附、划痕愈合和 Transwell 测定法对 A549 和 PC9 细胞进行功能实验。circ_0129047 的表达水平在 LAC 细胞和组织中降低。从机制上讲，我们发现 circ_0129047 可以海绵 miR-1206，miR-1206 可以直接靶向 BMPR2。此外，circ_0129047 或 BMPR2 敲低促进 LAC 细胞的活力、增殖、黏附、迁移和侵袭，同时抑制细胞凋亡。此外，circ_0129047 或 BMPR2 过表达对 LAC 细胞恶性表型的抑制作用可以通过过表达 miR-1206 来逆转。总之，circ_0129047 被发现对 LAC 进展具有肿瘤抑制作用；它通过海绵 miR-1206 上调 BMPR2 表达来抑制 LAC 进展。非小细胞肺癌（NSCLC）；小细胞肺癌（SCLC）；肺腺癌（LAC）；环状 RNA（circRNA）；微 RNA（miRNA）；骨形态发生蛋白（BMP）；鳞状细胞肺癌（SCC）；RNA 免疫沉淀（RIP）。
