A statistically inferred microRNA network identifies breast cancer target miR-940 as an actin cytoskeleton regulator

统计推断的microRNA网络鉴定出乳腺癌靶标miR-940是一种肌动蛋白细胞骨架调节因子。

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作者:Ricky Bhajun,Laurent Guyon,Amandine Pitaval,Eric Sulpice,Stéphanie Combe,Patricia Obeid,Vincent Haguet,Itebeddine Ghorbel,Christian Lajaunie,Xavier Gidrol

Abstract

MiRNAs are key regulators of gene expression. By binding to many genes, they create a complex network of gene co-regulation. Here, using a network-based approach, we identified miRNA hub groups by their close connections and common targets. In one cluster containing three miRNAs, miR-612, miR-661 and miR-940, the annotated functions of the co-regulated genes suggested a role in small GTPase signalling. Although the three members of this cluster targeted the same subset of predicted genes, we showed that their overexpression impacted cell fates differently. miR-661 demonstrated enhanced phosphorylation of myosin II and an increase in cell invasion, indicating a possible oncogenic miRNA. On the contrary, miR-612 and miR-940 inhibit phosphorylation of myosin II and cell invasion. Finally, expression profiling in human breast tissues showed that miR-940 was consistently downregulated in breast cancer tissues.

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