Department of Breast Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, 651 East Dongfeng Road, Guangzhou, 510060, China.
Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Queens, New York, 11439, USA.
Mol Cancer. 2019 Feb 11;18(1):23. doi: 10.1186/s12943-019-0946-x.
Increasing 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.
We 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.
qRT-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.
The 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.
越来越多的研究发现，环状 RNA（circRNAs）在癌症进展中发挥着重要作用。但是，circRNAs 在三阴性乳腺癌（TNBC）中的表达谱和功能尚不清楚。
我们使用 circRNA 微阵列来探索 TNBC 的 circRNA 表达谱。通过 qRT-PCR 在乳腺癌细胞系和组织中验证了 top 上调 circRNA circKIF4A 的表达。Kaplan-Meier 生存分析用于分析 circKIF4A 对 TNBC 的临床影响。进行了一系列实验来探索 circKIF4A 在 TNBC 进展中的作用，如细胞增殖和迁移。我们研究了 circKIF4A 对 miRNA 及其靶基因的调节作用，以探讨 circKIF4A 在 TNBC 中的潜在调节机制。
qRT-PCR 分析验证了 circKIF4A 显著上调，并与 TNBC 的较差生存相关。circKIF4A 的抑制抑制了 TNBC 中的细胞增殖和迁移。荧光素酶报告基因测定和 RNA 免疫沉淀测定揭示了 circKIF4A 和 KIF4A 可以与 miR-375 结合，并且 circKIF4A 通过海绵吸附 miR-375 来调节 KIF4A 的表达。
circKIF4A-miR-375-KIF4A 轴通过竞争性内源性 RNA（ceRNA）机制调节 TNBC 的进展。因此，circKIF4A 可以作为 TNBC 的预后生物标志物和治疗靶标。
