Department of Oncology, Xiantao First People's Hospital of Yangtze University, No. 29, Middle Section of Mianzhou Avenue, Xiantao, 433000, Hubei Province, People's Republic of China.
World J Surg Oncol. 2022 Jan 10;20(1):13. doi: 10.1186/s12957-021-02480-3.
Circular RNAs (circRNAs) are a novel type of endogenous RNAs and play vital roles in lung adenocarcinoma. However, the function and underlying mechanism of circ_0020850 in lung adenocarcinoma remain unknown.
The levels of circ_0020850, microRNA-326 (miR-326), and Beclin1 (BECN1) were analyzed by real-time quantitative polymerase chain reaction and western blot analyses. The migration and invasion were determined by wound healing and transwell assays, respectively. Colony formation assay was used to assess cell proliferation ability. The angiogenic ability was analyzed by Matrigel angiogenesis assay. The apoptosis rate was calculated by flow cytometry assay. Dual-luciferase reporter, RNA immunoprecipitation (RIP), and RNA pull-down assays were conducted to confirm the interaction relationship among circ_0020850, miR-326, and BECN1. A xenograft mice model was established to assess the role of circ_0020850 in vivo.
We found that circ_0020850 was obviously overexpressed in lung adenocarcinoma tissues and cells. Knockdown of circ_0020850 inhibited migration, invasion, proliferation, and angiogenesis but induced apoptosis in lung adenocarcinoma cells in vitro, as well as curbed tumor growth in vivo. MiR-326 was a target of circ_0020850, and knockdown of miR-326 abolished the suppression effect of circ_0020850 on the malignant behaviors of lung adenocarcinoma cells. Additionally, miR-326 could negatively regulate BECN1 expression, thereby regulating lung adenocarcinoma cell phenotypes. Importantly, circ_0020850 could directly bind to miR-326 and thus relieve miR-326-mediated inhibition on BECN1.
Circ_0020850 promoted the malignant development of lung adenocarcinoma by regulating miR-326/BECN1 axis, indicating that circ_0020850 might serve as a promising target for the diagnosis and treatment of lung adenocarcinoma patients.
环状 RNA（circRNAs）是一种新型的内源性 RNA，在肺腺癌中发挥着重要作用。然而，circ_0020850 在肺腺癌中的功能和潜在机制尚不清楚。
采用实时定量聚合酶链反应和 Western blot 分析检测 circ_0020850、microRNA-326（miR-326）和 Beclin1（BECN1）的水平。通过划痕愈合和 Transwell 测定分别检测迁移和侵袭。集落形成实验用于评估细胞增殖能力。Matrigel 血管生成实验分析血管生成能力。通过流式细胞术测定计算凋亡率。通过双荧光素酶报告、RNA 免疫沉淀（RIP）和 RNA 下拉实验证实 circ_0020850、miR-326 和 BECN1 之间的相互作用关系。建立异种移植小鼠模型评估 circ_0020850 在体内的作用。
我们发现 circ_0020850 在肺腺癌组织和细胞中明显过表达。circ_0020850 敲低抑制了肺腺癌细胞的迁移、侵袭、增殖和血管生成，但诱导了细胞凋亡，体内也抑制了肿瘤生长。miR-326 是 circ_0020850 的靶标，miR-326 敲低消除了 circ_0020850 对肺腺癌细胞恶性行为的抑制作用。此外，miR-326 可以负调控 BECN1 的表达，从而调节肺腺癌细胞表型。重要的是，circ_0020850 可以直接与 miR-326 结合，从而减轻 miR-326 对 BECN1 的抑制作用。
circ_0020850 通过调节 miR-326/BECN1 轴促进肺腺癌的恶性发展，表明 circ_0020850 可能成为肺腺癌患者诊断和治疗的有前途的靶点。
