Although it is known that the placement of genes in a cluster may be critical for proper expression patterns, it remains largely unclear whether the orders of members in an miRNA cluster have biological insights. By investigating the relationship between expression and orders for miRNAs from the oncogenic miR-17-92 cluster, we observed a highly ordered architecture in this cluster. A significant correlation between miRNA expression level and its placement was revealed. More importantly, the placement of these miRNAs is associated with their dysregulation in cancer. Here, we presented the opinion that miRNA clusters are not arranged randomly but show highly ordered architectures, which may have critical roles in physiology and pathology.
Genes are not randomly located in the genome. It is well known that many genes are organized as gene clusters in the genome, and the placement of the gene members in a cluster may have critical roles in biological insights. A typical example is the famous Hox gene family. The relative location of the gene members in the Hox gene cluster corresponds to an expression pattern along the cephalocaudal axis, which is critical for the proper placement of segment structures of animals during early embryonic development [
MicroRNAs (miRNAs) are one class of noncoding RNA genes, which mainly negatively regulate the expression of genes at the posttranscriptional level [
We obtained the miRNA expression profile in normal tissues from the study by Liang et al. [
Statistical computations were performed using
We analyzed the relationship between the placement of miRNA-17-92 cluster members and their expression levels using several public datasets. Each of the miRNA genes in this cluster contains two mature miRNAs being denoted as mature and mature star, respectively, that is, miR-17-5p and miR-17-3p (miR-17*). We first calculated the correlation between the miRNA placement and their expression level for the mature miRNAs in normal tissues from Liang et al.’s study [
Correlation between the member order of miR-17-92 cluster and their expression. (a) Correlation between the order of mature miRNA and miRNA expression in normal samples; (b) correlation between the order of mature star miRNA and miRNA expression in normal samples; (c) correlation between the order of mature miRNA and the dysregulation significance of these miRNAs in cancer samples; (d) correlation between the order of mature star miRNA and the dysregulation significance of these miRNAs in cancer samples.
We further asked whether the placement of miRNAs in a cluster has roles in pathology. To address this question, we compared the expression level of the six members (both mature miRNAs and mature star miRNAs) of miR-17-92 cluster in ovary cancer samples with that in normal ovary samples. As a result, the significance (
In summary, we found that the placement of miRNA members of an miRNA cluster has roles in determining the expression patterns of these miRNAs in both physiological and pathological processes. Furthermore, the mature miRNA and miRNA star miRNAs show different patterns. These results suggest that different members should have different biological functions and roles. Indeed, different researchers have obtained different observations. Using the
Bing Shi and Mingxuan Zhu have contributed equally to this work.
This work was supported by the Natural Science Foundation of China (Grant no. 30900829).