circKIF4A acts as a prognostic factor and mediator to regulate the progression of triple-negative breast cancer
circKIF4A acts as a prognostic factor and mediator to regulate the progression of triple-negative breast cancer
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circKIF4A 作为预后因素和调节三阴性乳腺癌进展的介质
DOI：
10.1186/s12943-019-0946-x
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发表时间：
2019-02-11
期刊：
影响因子：
37.3
通讯作者：
Xie, Xiaoming
中科院分区：
文献类型：
--
作者：
Tang, Hailin;Huang, Xiaojia;Xie, Xiaoming
背景越来越多的研究发现环状RNA（circular RNA，circRNA）在肿瘤的发生发展中起着重要作用。但三阴性乳腺癌（TNBC）中circRNA的表达谱和功能尚不清楚。方法我们使用circRNA微阵列来探索TNBC的circRNA表达谱。在乳腺癌细胞系和组织中，通过qRT-PCR证实了最高上调的circRNA，circKIF 4A的表达。进行Kaplan-Meier生存分析以分析circKIF 4A对TNBC的临床影响。进行了一系列实验以探索circKIF 4A在TNBC进展中的功能，例如细胞增殖和迁移。研究circKIF 4A对miRNA及其靶基因的调控作用，探讨circKIF 4A在TNBC中的潜在调控机制。circKIF 4A的抑制抑制TNBC中的细胞增殖和迁移。荧光素酶报告基因检测和RNA免疫沉淀实验表明，circKIF 4A和KIF 4A可与miR-375结合，circKIF 4A可通过海绵状作用调控KIF 4A的表达。结论circKIF 4A-miR-375-KIF 4A轴通过竞争性内源性RNA（ceRNA）机制调控TNBC的进展。因此，circKIF 4A可以作为TNBC的预后生物标志物和治疗靶标。
BackgroundIncreasing studies has found that circular RNAs (circRNAs) play vital roles in cancer progression. But the expression profile and function of circRNAs in triple-negative breast cancer (TNBC) are unclear.MethodsWe used a circRNA microarray to explore the circRNA expression profile of TNBC. The expression of the top upregulated circRNA, circKIF4A, was confirmed by qRT-PCR in breast cancer cell lines and tissues. Kaplan-Meier survival analysis was conducted to analyze the clinical impact of circKIF4A on TNBC. A series of experiments was performed to explore the functions of circKIF4A in TNBC progression, such as cell proliferation and migration. We investigated the regulatory effect of circKIF4A on miRNA and its target genes to explore the potential regulatory mechanisms of circKIF4A in TNBC.ResultsqRT-PCR analyses verified that circKIF4A was significantly upregulated and positively associated with poorer survival of TNBC. The inhibition of circKIF4A suppressed cell proliferation and migration in TNBC. Luciferase reporter assay and RNA immunoprecipitation assay revealed that circKIF4A and KIF4A could bind to miR-375 and that circKIF4A regulated the expression of KIF4A via sponging miR-375.ConclusionsThe circKIF4A-miR-375-KIF4A axis regulates TNBC progression via the competitive endogenous RNA (ceRNA) mechanism. circKIF4A may therefore serve as a prognostic biomarker and therapeutic target for TNBC.