Luqing Zhao1, Yuelong Zhao2, Yanong He2, Qingling Li1, Yitao Mao3. 1. Department of Pathology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China; Department of Pathology, School of Basic Medical Science, Xiangya School of Medicine, Central South University, Changsha, Hunan 410013, China. 2. School of Computer Science and Engineering, South China University of Technology, Guangzhou, Guangdong 510640, China. 3. Department of Radiology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China. Electronic address: maoyt@csu.edu.cn.
Abstract
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.
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 cancerpatients. 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 cancerpatients. 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 cancerpatients. LncRNAs (XIST, H19 and MALAT1) directly bound to hsa-miR-20a and were negatively correlated with hsa-miR-20a expression in breast cancerpatient 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.