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CCL18通过 N-Ras/c-myc/lin28下调乳腺癌细胞 miR98的表达

赵瑞华 李向柯 姜文静 张伟杰 宗红

西安交通大学学报(医学版)Issue(6):775-781,7.
西安交通大学学报(医学版)Issue(6):775-781,7.DOI:10.7652/jdyxb201506012

CCL18通过 N-Ras/c-myc/lin28下调乳腺癌细胞 miR98的表达

CCL18 downregulates the expression of miR98 in breast cancer cells via N-Ras/c-myc/lin28 pathway

赵瑞华 1李向柯 1姜文静 1张伟杰 1宗红1

作者信息

  • 1. 郑州大学第一附属医院肿瘤科,河南省高等学校临床医学重点学科开放实验室,河南郑州 450052
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摘要

Abstract

Objective To explore whether CCL18 is involved in regulating the expression of miRNAs in breast cancer.Methods The expression profile of miRNAs in the breast cancer cell following CCL18 treatment was determined by miRNAs microarray analysis.Then we performed QRT-PCR and Luciferase Reporter Assay to validate the results from the miRNAs microassay.We used transient transfection to change the expression of miR98 and c-myc in breast cancer cells.We then used QRT-PCR and Western blot to analyze the mechanism by which CCL18 downregulates the expression of miR98 in breast cancer cells.Results miRNAs microarray analysis showed that cells treated with CCL18 differentially expressed 20 miRNAs genes compared with those in the control group. Our QRT-PCR and Luciferase Reporter Assay confirmed the result.The mRNA and protein expressions of C-myc and lin28 were increased after CCL18 stimulation in breast cancer cells.Transfection with c-myc siRNAs rescued the increase of lin28 and loss of miR98 expression caused by CCL18 stimulation.Our results also showed that CCL18 could upregulate the expression of N-Ras at post-transcription level.Conclusion CCL18 downregulates the expression of miR98 via N-Ras/c-myc/lin28 pathway.The downregulated miR98 increases the expression of N-Ras after transfection,which further activates c-myc/lin28 pathway and forms a positive feedback loop.

关键词

CCL18/乳腺癌/miR98/miRNA/c-myc/N-Ras/lin28

Key words

CCL18/breast cancer/miR98/miRNA/c-myc/N-Ras/lin28

分类

医药卫生

引用本文复制引用

赵瑞华,李向柯,姜文静,张伟杰,宗红..CCL18通过 N-Ras/c-myc/lin28下调乳腺癌细胞 miR98的表达[J].西安交通大学学报(医学版),2015,(6):775-781,7.

基金项目

郑州大学第一附属医院院内青年基金资助项目Supported by the Young Scientists Foundation of the First Affiliated Hospital of Zhengzhou University ()

西安交通大学学报(医学版)

OA北大核心CSCDCSTPCD

1671-8259

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