Interpreting the MicroRNA-15/107 family: interaction identification by combining network based and experiment supported approach

Interpreting the MicroRNA-15/107 family: interaction identification by combining network based and experiment supported approach
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解读 MicroRNA-15/107 家族:结合基于网络和实验支持的方法进行相互作用识别

DOI:
10.1186/s12881-019-0824-9
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发表时间:
2019
影响因子:
--
通讯作者:
Lu Shemin
Lu Shemin
中科院分区:
医学4区
文献类型:
--
作者:
Wang Si;Zhu Wenhua;Xu Jing;Guo Yuanxu;Yan Jidong;Meng Liesu;Jiang Congshan;Lu Shemin

文献摘要

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研究背景高度保守的miR-15/107家族(又称miR-15/107基因组)包括10个miRNA成员,目前被认为与多种人类疾病密切相关。一些研究关注整个家族而不是单个miRNA以获得更大的图景,而某些单个miRNA甚至在同一疾病中也存在一定的签名失调。方法面对实验证据的指数增长,本研究试图利用各种生物信息学工具分析它们的功能和靶点相互作用。描述了进化保守的“AGCAGC”序列和可能的成簇转录模式。其次,分析整个家族的实验验证和生物信息学预测的miRNA-靶基因关系,以了解miR-15/107家族靶调控的潜在集体效应的机制。此外,进行了miR-15/107家族之间的通路分析并详细展示,同时实验验证了其对细胞增殖的影响。结论miR-15/107家族在人类多种疾病中的共同功能和意义是依靠大量重叠的靶基因实现的。虽然家族成员之间靶基因相互作用的微小差异也可以解释某些个体miRNA在疾病特异性失调和多种参与途径等方面的特征行为。
BackgroundThe highly conservative miR-15/107 family (also named as miR-15/107 gene group) including ten miRNA members is currently recognized strongly implicated in multiple human disorders. Some studies focus on the entire family rather than individual miRNA for a bigger picture, while there is also certain signature dysregulation for some of the individual miRNA implicated even in the same disorder.MethodsFaced with the exponential growth of experimental evidence, our study tries to analyze their function and target interactions using various bioinformatics tools.ResultsFirstly, the evolutionary conservative “AGCAGC” sequence and possible clustered transcriptional pattern were described. Secondly, both the experimentally validated and bioinformatically predicted miRNA-target gene relationship of the entire family was analyzed to understand the mechanism of underlying collective effects for target regulation from the miR-15/107 family. Moreover, pathway analysis among miR-15/107 family was performed and displayed in detail, while its impact on cell proliferation is experimentally validated. Eventually, the dysregulation of miR-15/107 in diseases was discussed.ConclusionsIn summary, our study proposes that the collective functions and implication of miR-15/107 family in various human diseases are achieved relying on the massive overlapping target genes. While the minor differences within target gene interaction among family members could also explain the signature behavior for some of the individual miRNA in aspects such as its disease-specific dysregulation and various participation in pathways.