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The functional pathway analysis and clinical significance of miR-20a and its related lncRNAs in breast cancer
Cellular Signalling ( IF 4.4 ) Pub Date : 2018-08-06 , DOI: 10.1016/j.cellsig.2018.08.004
Luqing Zhao , Yuelong Zhao , Yanong He , Qingling Li , Yitao Mao

Background

miR-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.

Methods

The 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.

Results

The 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.

Conclusions

Taken 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.



中文翻译:

miR-20a及其相关lncRNA在乳腺癌中的功能通路分析及其临床意义

背景

miR-20a是各种生物学过程和癌症进展程序中的关键分子。然而,它与lncRNA的关系及其在乳腺肿瘤发生中的功能途径分析的研究较少。

方法

来自TCGA数据库的表达数据和多种生物信息学资源被用于检查miR-20a及其相关lncRNA(XIST,H19和MALAT1)在乳腺癌患者中的表达水平,存活曲线,相互作用和功能说明。荧光素酶报告基因分析和Pearson相关分析被用于验证miR-20a和三种lncRNA(XIST,H19和MALAT1)之间的直接调控关系。进行了体外细胞增殖,迁移和侵袭试验,以检查miR-20a和XIST在不同乳腺癌细胞系中的生物学作用。进行了受试者工作特征曲线(ROC)分析,以评估乳腺癌患者血清miR-20a和XIST的诊断价值。

结果

在乳腺癌样品和血清样品中,miR-20a表达均显着上调,并且与乳腺癌患者的不良存活率相关。LncRNA(XIST,H19和MALAT1)直接与hsa-miR-20a结合,并与乳腺癌患者样品中的hsa-miR-20a表达负相关。为了进行功能说明和下游信号通路分析,XIST,H19和MALAT1主要共享其在乳腺癌进展中的细胞运动性和白介素信号传导中的调节功能。此外,miR-20a的过表达和XIST的抑制促进了体外乳腺癌细胞的生长,迁移和侵袭,血清miR-20a和XIST作为ROC曲线下面积(AUC)为乳腺癌的潜在诊断生物标志物。 0.87(95%CI = 0.78至0.97)和0.78(95%CI = 0.67至0)。

结论

综上所述,这些发现为我们提供了利用miR-20a及其相关lncRNA作为潜在的诊断生物标志物和有希望的乳腺癌治疗靶标的新颖见解和途径。

更新日期:2018-08-06
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