环状 RNA BIRC6 通过海绵吸附 microRNA-145 促进非小细胞肺癌细胞的进展。
CircRNA BIRC6 promotes non-small cell lung cancer cell progression by sponging microRNA-145.
机构信息
Department of Chemoradiation Oncology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
Department of Radiology, The First Affiliated Hospital of Wenzhou Medical University, South Bai-xiang street, Ouhai District, Wenzhou, 325000, Zhejiang, China.
出版信息
Cell Oncol (Dordr). 2020 Jun;43(3):477-488. doi: 10.1007/s13402-020-00503-x. Epub 2020 Apr 15.
PURPOSE
Non-small cell lung cancer (NSCLC) is a leading cause of cancer-related mortality world-wide. Recently, a number of circular RNAs (circRNAs) has been found to be differentially expressed in human NSCLCs, correlating with clinico-pathological features. As yet, the expression and potential role of circRNA BIRC6 (circBIRC6) in NSCLC have not been studied.
METHODS
Expression of circBIRC6 and its target microRNA-145 (miR-145) in human NSCLC cells and tissues was assessed using qRT-PCR. In vitro genetic strategies were used to exogenously alter circBIRC6 and miR-145 expression. Their impact on in vitro and in vivo NSCLC cell behavior was studied.
RESULTS
We found that circBIRC6 was upregulated in primary human NSCLC tissues and NSCLC cells, whereas its potential target, miR-145, was downregulated. In A549 NSCLC cells and primary human NSCLC cells, shRNA-induced silencing of circBIRC6 potently inhibited their growth, proliferation, migration and invasion. Conversely, we found that exogenous overexpression of circBIRC6 promoted these characteristics. Using RNA immunoprecipitation (RIP) in A549 cells, we found that Argonaute 2 (Ago2) immunoprecipitated together with both circBIRC6 and miR-145. Additional studies revealed that the miR-145 level increased after circBIRC6 silencing in A549 cells, but decreased after circBIRC6 overexpression. Of note, we found that the circBIRC6 silencing-induced anti-A549 activity could be attenuated by a miR-145 inhibitor. Lastly, we found that circBIRC6 silencing inhibited the growth of NSCLC xenografts in severe combined immunodeficient mice.
CONCLUSIONS
From our data we conclude that circBIRC6 overexpression promotes NSCLC cell progression, possibly by sponging miR-145.
目的
非小细胞肺癌（NSCLC）是全球癌症相关死亡的主要原因。最近，研究发现许多环状 RNA（circRNA）在人类 NSCLC 中表达差异，并与临床病理特征相关。然而，circRNA BIRC6（circBIRC6）在 NSCLC 中的表达和潜在作用尚未研究。
方法
采用 qRT-PCR 检测人 NSCLC 细胞和组织中 circBIRC6及其靶微小 RNA-145（miR-145）的表达。采用体外遗传策略改变 circBIRC6 和 miR-145 的表达。研究其对体外和体内 NSCLC 细胞行为的影响。
结果
我们发现 circBIRC6 在人原发性 NSCLC 组织和 NSCLC 细胞中上调，而其潜在靶标 miR-145 下调。在 A549 NSCLC 细胞和原发性人 NSCLC 细胞中，shRNA 诱导的 circBIRC6 沉默强烈抑制其生长、增殖、迁移和侵袭。相反，我们发现外源性过表达 circBIRC6 促进了这些特征。在 A549 细胞中，用 RNA 免疫沉淀（RIP）发现 Argonaute 2（Ago2）与 circBIRC6 和 miR-145 共同免疫沉淀。进一步的研究表明，circBIRC6 沉默后 A549 细胞中的 miR-145 水平增加，但 circBIRC6 过表达后降低。值得注意的是，我们发现 circBIRC6 沉默诱导的抗 A549 活性可被 miR-145 抑制剂减弱。最后，我们发现 circBIRC6 沉默抑制了严重联合免疫缺陷小鼠 NSCLC 异种移植的生长。
结论
我们的数据表明，circBIRC6 的过表达促进 NSCLC 细胞的进展，可能通过海绵吸附 miR-145。
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