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Review
. 2021 Mar 25;40(1):112.
doi: 10.1186/s13046-021-01910-0.

ChrXq27.3 miRNA cluster functions in cancer development

Kosuke Yoshida  1   2   3 , Akira Yokoi  4   5 , Yusuke Yamamoto  3 , Hiroaki Kajiyama  1
Affiliations
Review

ChrXq27.3 miRNA cluster functions in cancer development

Kosuke Yoshida et al. J Exp Clin Cancer Res. .

Abstract

MicroRNAs (miRNAs) regulate the expression of their target genes post-transcriptionally; thus, they are deeply involved in fundamental biological processes. miRNA clusters contain two or more miRNA-encoding genes, and these miRNAs are usually coexpressed due to common expression mechanisms. Therefore, miRNA clusters are effective modulators of biological pathways by the members coordinately regulating their multiple target genes, and an miRNA cluster located on the X chromosome q27.3 region has received much attention in cancer research recently. In this review, we discuss the novel findings of the chrXq27.3 miRNA cluster in various types of cancer.The chrXq27.3 miRNA cluster contains 30 mature miRNAs synthesized from 22 miRNA-encoding genes in an ~ 1.3-Mb region. The expressions of these miRNAs are usually negligible in many normal tissues, with the male reproductive system being an exception. In cancer tissues, each miRNA is dysregulated, compared with in adjacent normal tissues. The miRNA-encoding genes are not uniformly distributed in the region, and they are further divided into two groups (the miR-506-514 and miR-888-892 groups) according to their location on the genome. Most of the miRNAs in the former group are tumor-suppressive miRNAs that are further downregulated in various cancers compared with normal tissues. miR-506-3p in particular is the most well-known miRNA in this cluster, and it has various tumor-suppressive functions associated with the epithelial-mesenchymal transition, proliferation, and drug resistance. Moreover, other miRNAs, such as miR-508-3p and miR-509-3p, have similar tumor-suppressive effects. Hence, the expression of these miRNAs is clinically favorable as prognostic factors in various cancers. However, the functions of the latter group are less understood. In the latter group, miR-888-5p displays oncogenic functions, whereas miR-892b is tumor suppressive. Therefore, the functions of the miR-888-892 group are considered to be cell type- or tissue-specific.In conclusion, the chrXq27.3 miRNA cluster is a critical regulator of cancer progression, and the miRNAs themselves, their regulatory mechanisms, and their target genes might be promising therapeutic targets.

Keywords: Drug-resistance; Epithelial–mesenchymal transition; Proliferation; X chromosome; miR-506-3p; miR-888-5p; miRNA; miRNA cluster.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Fig. 1
Fig. 1
Schema of the chrXq27.3 miRNA cluster and sequence similarity of the miRNAs in the cluster There are 22 miRNA-encoding genes in the chrXq27.3 cluster, and they are divided into two groups according to their location. Mature forms of the miRNAs with close loci tend to have similar sequences
Fig. 2
Fig. 2
Tumor-suppressive roles of the chrXq27.3 miRNA cluster Many miRNAs in the cluster act as tumor suppressors by targeting various genes involved in the epithelial–mesenchymal transition and proliferation. Previously validated interactions between the miRNAs and genes or non-cording RNAs are described
Fig. 3
Fig. 3
Treatment resistance and the chrXq27.3 miRNA cluster Several miRNAs in the cluster are involved in treatment resistance, and their previously validated functions are described
Fig. 4
Fig. 4
Tumor-promotive roles of the chrXq27.3 miRNA cluster Some miRNAs in the cluster also act in an oncogenic manner by targeting various genes. Previously validated interactions between the miRNAs and genes or non-cording RNAs are described
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