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

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。mi RNA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mi RNA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mi RNA组数据中筛选出与之负相关的11个mi RNA,包括mi R-130a-3p、mi R-130b-3p、mi R-125a-5p、mi R-30a-3p、mi R-195-5p、mi R-345-5p、mi R-509-3-5p、mi R-374a-5p、mi R-509-5p、mi R-148a-3p和mi R-330-3p。经过生物信息学分析mi RNA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mi RNA进行分子生物学验证,发现mi R-195-5p、mi R-130a-3p、mi R-509-5p和mi R-509-3-5p共4个可以调节重要肿瘤基因的mi RNA。本研究运用m RNA和mi RNA两种转录组的测序数据筛选EMT相关mi RNA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。

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 m RNA and mi RNA 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 mi RNAs including mi R-130a-3p, mi R-130b-3p, mi R-125a-5p, mi R-30a-3p, mi R-195-5p, mi R-345-5p, mi R-509-3-5p, mi R-374a-5p, mi R-509-5p, mi R-148a-3p and mi R-330-3p, negatively related with EMT genes using the Mirsystem software. Bioinformatics analysis with target genes of these mi RNAs 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 mi RNAs with molecular biology experiments demonstrated that four mi RNAs regulated oncogenes in melanomas, including mi R-195-5p, mi R-130a-3p, mi R-509-5p, and mi R-509-3-5p. Our study integrates two kinds of omics data to screen for EMT-related mi RNAs, providing a new research idea in the precision genomics of cancer research.