The functional pathway analysis and clinical significance of miR-20a and its related lncRNAs in breast cancer
The functional pathway analysis and clinical significance of miR-20a and its related lncRNAs in breast cancer
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miR-20a及其相关lncRNA在乳腺癌中的功能通路分析及临床意义
DOI：
10.1016/j.cellsig.2018.08.004
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发表时间：
2018
影响因子：
4.8
通讯作者：
Mao Yitao
中科院分区：
文献类型：
--
作者：
Zhao Luqing;Zhao Yuelong;He Yanong;Li Qingling;Mao Yitao
背景miR-20 a是多种生物学过程和癌症进展过程中的关键分子。方法利用TCGA数据库和多种生物信息学资源，分析miR-20 a及其相关lncRNAs（XIST、H19和MALAT 1）在乳腺癌患者中的表达水平、生存曲线、相互作用和功能图解。利用荧光素酶报告基因分析和Pearson相关分析验证miR-20 a与三种lncRNA（XIST、H19和MALAT 1）之间的直接调控关系。进行体外细胞增殖、迁移和侵袭测定以检查miR-20 a和XIST在不同乳腺癌细胞系中的生物学效应。结果miR-20 a在乳腺癌组织和血清中的表达均显著上调，且与乳腺癌患者的不良生存率相关。LncRNA（XIST、H19和MALAT 1）直接与hsa-miR-20 a结合，并与乳腺癌患者样本中的hsa-miR-20 a表达呈负相关。对于功能说明和下游信号通路分析，XIST，H19和MALAT 1主要在乳腺癌进展中的细胞运动和白细胞介素信号转导中共享它们的调节功能。另外，miR-20 a的过表达和XIST的抑制在体外促进乳腺癌细胞的生长、迁移和侵袭，血清miR-20 a和XIST可作为乳腺癌的潜在诊断生物标志物，其ROC曲线下面积（AUC）为0.87结论miR-20 a及其相关的lncRNA为乳腺癌的诊断和治疗提供了新的思路和途径。
BackgroundmiR-20a is a critical molecule in various biological processes and cancer progression procedures. However, its relationships with lncRNAs and their functional pathway analysis in breast tumorigenesis are less intensively studied.MethodsThe expression data from TCGA database and multiple bioinformatics resources were used to check the expression levels, survival curves, interactions and functional illustrations of miR-20a and its related lncRNAs (XIST, H19 and MALAT1) in breast cancer patients. The luciferase reporter assays and Pearson's correlation analyses were utilized to verify the direct regulatory relationship between miR-20a and three lncRNAs (XIST, H19 and MALAT1). In vitro cell proliferation, migration and invasion assays, were performed to check the biological effects of miR-20a and XIST in different breast cancer cell lines. The receiver operating characteristic curve (ROC) analyses were done for evaluating diagnostic values of serum miR-20a and XIST in breast cancer patients.ResultsThe miR-20a expression was significantly up-regulated in both breast cancer samples and serum samples, and correlated with poor survival rate in breast cancer patients. LncRNAs (XIST, H19 and MALAT1) directly bound to hsa-miR-20a and were negatively correlated with hsa-miR-20a expression in breast cancer patient samples. For functional illustrations and downstream signaling pathways analysis, XIST, H19 and MALAT1 mainly shared their regulatory functions in cell motility and interleukin signaling in breast cancer progression. Additionally, over-expression of miR-20a and inhibition of XIST promoted breast cancer cell growth, migration and invasion in vitro, and serum miR-20a and XIST served as potential diagnostic biomarkers for breast cancer with the area under ROC curve (AUC) of 0.87 (95% CI = 0.78 to 0.97), and 0.78 (95% CI = 0.67 to 0.89) respectively.ConclusionsTaken together, these findings provide us novel insights and avenues for utilizing miR-20a and its related lncRNAs as potential diagnostic biomarkers and promising therapeutic targets for breast cancer treatment.