环状RNA circ_0005230表达增加提示乳腺癌预后不良，并通过miR-618/CBX8信号通路调控细胞增殖和侵袭。
Increased Expression of Circular RNA circ_0005230 Indicates Dismal Prognosis in Breast Cancer and Regulates Cell Proliferation and Invasion via miR-618/ CBX8 Signal Pathway.
作者信息
Xu Yi, Yao Yue, Leng Kaiming, Ji Daolin, Qu Lijun, Liu Yueping, Cui Yunfu
机构信息
Department of Hepatopancreatobiliary Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin, China.
The Key Laboratory of Myocardial Ischemia, Harbin Medical University, Ministry of Education, Harbin, China.
出版信息
Cell Physiol Biochem. 2018;51(4):1710-1722. doi: 10.1159/000495675. Epub 2018 Nov 30.
BACKGROUND/AIMS: Circular RNAs (circRNAs) are a class of non-coding RNAs. They have been proved to be critically involved in tumorigenesis and progression of malignancies through competing endogenous RNA (ceRNA) mechanism. Nevertheless, the exploration between circRNAs and pathogenesis of breast cancer (BC) is limited. Previously, circ_0005230 was identified upregulated in BC tissues screened by circRNA microarray. In the present study, we aimed to investigate the expression pattern, functional role, and mechanism of circ_0005230 in BC.
METHODS
qRT-PCR was conducted to elucidate the expression levels of circ_0005230 in BC tissues and cells. Additionally, the clinical severity and prognostic value were investigated. CCK-8, colony-forming, flow cytometric assays were performed. Animal study was conducted to validate the in vitro data. What's more, Transwell assays were induced to detect the cell metastatic properties of circ_0005230 exerts in BC cells. Luciferase reporter assay was used to measure the mechanism of circ_0005230.
RESULTS
circ_0005230 was overexpressed in BC tissue specimens and cell lines. The overexpression of circ_0005230 was related to adverse phenotypes in the patients with BC. In addition, circ_0005230 could be regarded as a prognostic predictor in BC patients. In vitro and in vivo data demonstrated the cell growth promoting role of circ_0005230. Moreover, circ_0005230 could also promote cell migratory and invasive capacities. For the mechanism investigation, circ_0005230 was proved to be a sponge of miR-618, and expression of miR-618 could regulate CBX8 expression via targeting the 3'UTR of CBX8. Rescue assays also illustrated an oncogenic function of circ_0005230 in BC via acting as a miR-618 sponge to promote CBX8 expression.
CONCLUSION
circ_0005230/miR-618/CBX8 axis might play a key role in BC tumorigenesis and development.
背景/目的：环状RNA（circRNAs）是一类非编码RNA。它们已被证明通过竞争性内源RNA（ceRNA）机制在恶性肿瘤的发生和发展中起关键作用。然而，circRNAs与乳腺癌（BC）发病机制之间的探索有限。此前，通过circRNA芯片筛选发现circ_0005230在BC组织中上调。在本研究中，我们旨在研究circ_0005230在BC中的表达模式、功能作用及机制。
方法
采用qRT-PCR检测circ_0005230在BC组织和细胞中的表达水平。此外，研究其临床严重程度和预后价值。进行CCK-8、集落形成、流式细胞术检测。开展动物实验以验证体外实验数据。另外，进行Transwell检测以检测circ_0005230对BC细胞的细胞转移特性的影响。采用荧光素酶报告基因检测来探究circ_0005230的作用机制。
结果
circ_0005230在BC组织标本和细胞系中过表达。circ_0005230的过表达与BC患者的不良表型相关。此外，circ_0005230可被视为BC患者的预后预测指标。体外和体内实验数据表明circ_0005230具有促进细胞生长的作用。此外，circ_0005230还可促进细胞迁移和侵袭能力。机制研究表明，circ_0005230是miR-618的海绵，miR-618的表达可通过靶向CBX8的3'UTR来调节CBX8的表达。挽救实验也表明circ_0005230在BC中通过作为miR-618的海绵促进CBX8表达而发挥致癌作用。
结论
circ_0005230/miR-618/CBX8轴可能在BC的发生和发展中起关键作用。
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