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解读微小RNA-15/107家族:结合基于网络和实验支持的方法进行相互作用鉴定

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

作者信息

Wang Si, Zhu Wenhua, Xu Jing, Guo Yuanxu, Yan Jidong, Meng Liesu, Jiang Congshan, Lu Shemin

机构信息

Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, 710061, People's Republic of China.

Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University), Ministry of Education, Xi'an, Shaanxi, 710061, People's Republic of China.

出版信息

BMC Med Genet. 2019 May 31;20(1):96. doi: 10.1186/s12881-019-0824-9.

Abstract

BACKGROUND

The 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.

METHODS

Faced with the exponential growth of experimental evidence, our study tries to analyze their function and target interactions using various bioinformatics tools.

RESULTS

Firstly, 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.

CONCLUSIONS

In 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.

摘要

背景

高度保守的miR-15/107家族(也称为miR-15/107基因组)包含10个miRNA成员,目前被认为与多种人类疾病密切相关。一些研究着眼于整个家族而非单个miRNA以获得更全面的认识,然而即使在同一疾病中,某些单个miRNA也存在特定的失调特征。

方法

面对实验证据的指数级增长,我们的研究试图使用各种生物信息学工具分析它们的功能和靶标相互作用。

结果

首先,描述了进化保守的“AGCAGC”序列和可能的簇状转录模式。其次,分析了整个家族经过实验验证和通过生物信息学预测的miRNA-靶基因关系,以了解miR-15/107家族对靶标调控的潜在集体效应机制。此外,对miR-15/107家族进行了通路分析并详细展示,同时通过实验验证了其对细胞增殖的影响。最后,讨论了miR-15/107在疾病中的失调情况。

结论

总之,我们的研究表明,miR-15/107家族在各种人类疾病中的集体功能和影响是通过大量重叠的靶基因实现的。而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单个miRNA在疾病特异性失调和参与各种通路等方面的特征行为。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d69/6544937/65123be3819f/12881_2019_824_Fig1_HTML.jpg

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