miRNA调控恶性黑色素瘤细胞上皮-间充质转化的分子网络及机制

doi:10.16288/j.yczz.15-022

遗传 ›› 2015, Vol. 37 ›› Issue (7): 673-682.doi: 10.16288/j.yczz.15-022

miRNA调控恶性黑色素瘤细胞上皮-间充质转化的分子网络及机制

王冬^{1, 4}, 李永君², 丁楠^{2, 3}, 王均云^{2, 3}, 杨琼^{2, 3}, 杨雅冉², 李艳明^{2, 3}, 方向东², 赵华¹

1. 中国人民解放军总医院皮肤科,北京 100853;
2. 中国科学院北京基因组研究所,中国科学院基因组科学与信息重点实验室,北京 100101;
3. 中国科学院大学,北京 100049;
4. 解放军第309医院,北京 100091

收稿日期:2015-01-18 修回日期:2015-04-01 出版日期:2015-07-20 发布日期:2015-07-20
通讯作者: 赵华,博士,主任医师,研究方向：皮肤肿瘤及变态反应性皮肤病。E-mail: luckhua301@163.com
作者简介:王冬,在读博士研究生,专业方向：恶性肿瘤的表观遗传学研究。Tel: 010-84097538;E-mail: wangdong@big.ac.cn;李永君,副研究员,专业方向：分子生物学。Tel: 010-84097538;E-mail: yjli@big.ac.cn。王冬和李永君为并列第一作者。
基金资助:
国家自然科学基金面上项目(编号：31471236)和国家高技术研究发展计划项目(863计划)(编号：2012AA022502)资助

Molecular networks and mechanisms of epithelial-mesenchymal transition regulated by miRNAs in the malignant melanoma cell line

Dong Wang^{1, 4}, Yongjun Li², Nan Ding^{2, 3}, Junyun Wang^{2, 3}, Qiong Yang^{2, 3}, Yaran Yang², Yanming Li^{2, 3}, Xiangdong Fang², Hua Zhao¹

1. Department of Dermatology, General Hospital of People's Liberation Army, Beijing 100853, China;
2. CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China;
3. University of Chinese Academy of Sciences, Beijing 100049, China;
4. The 309th Hospital of China People’
s Liberation Army, Beijing 100091, China

Received:2015-01-18 Revised:2015-04-01 Online:2015-07-20 Published:2015-07-20

摘要/Abstract

摘要： 黑色素瘤是一种极易发生转移的恶性皮肤肿瘤,具有高度的致死性。上皮-间充质细胞转化(Epithelial-mesenchymal transition, EMT)在胚胎发育过程中起到非常重要的作用,同时在肿瘤的发生和恶化过程中也扮演着重要的角色。miRNA具有广谱的调节能力,对于肿瘤发生和EMT形成都能产生不同程度的影响。本文整合黑色素瘤细胞系转录组和miRNA组测序数据,在转录组数据中筛选得到参与肿瘤EMT过程的基因,通过Mirsystem软件预测并从miRNA组数据中筛选出与之负相关的11个miRNA,包括miR-130a-3p、miR-130b-3p、miR-125a-5p、miR-30a-3p、miR-195-5p、miR-345-5p、miR-509-3-5p、miR-374a-5p、miR-509-5p、miR-148a-3p和miR-330-3p。经过生物信息学分析miRNA靶基因富集的分子网络和信号途径,发现了两个与细胞发育和细胞间相互作用密切相关的网络,以及多个参与调控EMT过程的信号通路。对11个miRNA进行分子生物学验证,发现miR-195-5p、miR-130a-3p、miR-509-5p和miR-509-3-5p共4个可以调节重要肿瘤基因的miRNA。本研究运用mRNA和miRNA两种转录组的测序数据筛选EMT相关miRNA的方法,为肿瘤多组学数据整合分析提供了新的研究思路,并以期能为肿瘤精准基因组学的发展发挥重要的推进作用。

关键词: 黑素色瘤, 转录组, miRNA组, 上皮-间充质细胞转化

Abstract: Melanoma is a malignant cutaneous cancer of high metastasis and lethal rates. Epithelial-mesenchymal transition (EMT) plays an important role in the embryonic developmental process that is often activated during tumorigenesis and metastasis. In this study, we integrated of mRNA and miRNA transcriptome sequencing data of melanocyte and melanoma cell lines to identify genes involved in the process of tumor EMT in the first place, and uncovered 11 miRNAs including miR-130a-3p, miR-130b-3p, miR-125a-5p, miR-30a-3p, miR-195-5p, miR-345-5p, miR-509-3-5p, miR-374a-5p, miR-509-5p, miR-148a-3p and miR-330-3p, negatively related with EMT genes using the Mirsystem software. Bioinformatics analysis with target genes of these miRNAs revealed two networks closely related with cellular development and cell-to-cell interactions, as well as multiple signaling pathways participating in EMT. Validation of the 11 miRNAs with molecular biology experiments demonstrated that four miRNAs regulated oncogenes in melanomas, including miR-195-5p, miR-130a-3p, miR-509-5p, and miR-509-3-5p. Our study integrates two kinds of omics data to screen for EMT-related miRNAs, providing a new research idea in the precision genomics of cancer research.

Key words: melanoma, transcriptome, miRNAome, epithelial-mesenchymal transition

王冬, 李永君, 丁楠, 王均云, 杨琼, 杨雅冉, 李艳明, 方向东, 赵华. miRNA调控恶性黑色素瘤细胞上皮-间充质转化的分子网络及机制[J]. 遗传, 2015, 37(7): 673-682.

Dong Wang, Yongjun Li, Nan Ding, Junyun Wang, Qiong Yang, Yaran Yang, Yanming Li, Xiangdong Fang, Hua Zhao. Molecular networks and mechanisms of epithelial-mesenchymal transition regulated by miRNAs in the malignant melanoma cell line[J]. HEREDITAS(Beijing), 2015, 37(7): 673-682.

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miRNA调控恶性黑色素瘤细胞上皮-间充质转化的分子网络及机制

Molecular networks and mechanisms of epithelial-mesenchymal transition regulated by miRNAs in the malignant melanoma cell line

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