MicroRNA Clusters -A Tip of the Iceberg in Cancer Therapy

Zhongliang Ma*; Xianyi Wang

doi:https://doi.org/10.1057/jio000003

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Editorial

MicroRNA Clusters -A Tip of the Iceberg in Cancer Therapy

Zhongliang Ma*,

Xianyi Wang

Journal of Investigative Oncology [2020; 1(1):11-12]

DOI: https://doi.org/10.1057/jio000003

Received: 02 May 2020, Accepted: 06 May 2020, Published: 13 May 2020

The noncoding regions of human genome are transcribed into thousands of RNA molecules. The first microRNA, lin-4 was reported in 1993, but it came to a research spot until let-7 was confirmed in 2000. Now, vital roles noncoding RNAs in the development of cancer have been recognized [1]. Noncoding RNAs, such as miRNAs, tRNA-derived fragments (tRF), circRNAs and long noncoding RNAs (lncRNAs) as key players in metabolic diseases, especially tumorigenesis.

Key words:

Noncoding RNA clusters; Cancer therapy; miRNA clusters

*Corresponding Author:

Dr. Zhongliang Ma, Lab for Noncoding RNA & Cancer, School of Life Sciences, Shanghai University, 200444 Shanghai, China; E-mail: zlma@shu.edu.cn

EDITORIAL

A great deal of miRNAs is localized as clusters in the genome, whose transcripts are closely adjacent physically. Because a single miRNA could regulate the expression of many different genes, a miRNA cluster that containing more than two miRNAs will regulate gene expression more widely. MiRNA clusters can be divided into homologous clusters and heterologous clusters. The former consists of miRNAs from the same family, while the latter members come from different families [2]. Many miRNA clusters have been defined currently, among which the miR-17-92 cluster, miR-183 cluster and miR-34 family play key roles in oncogenesis.

In cancer therapy, drug resistance is associated with a variety of biological progress, including autophagy, oxidative stress, DNA repair and the regulation of tumor microenvironment in which miRNA clusters play important parts and control the key genes expression involved in these physiological processes [3, 4]. Different noncoding RNA expression profile in specific tumors has been detected through RNA-seq technology. They can regulate cell proliferation, migration, invasion, apoptosis, cell cycle, epithelial-mesenchymal transition, etc [5]. The cross talk between miRNA clusters (inter- and intra cluster interactions) is essential for oncogenesis. For example, the members of miR-17-92 cluster interact with each other and regulate anti‐oncogenic or oncogenic signalling pathways together. However, the precise mechanism between miRNA clusters remains to be further explored.

MiR-34 family has three members, miR-34a, and miR-34b and miR-34c. The latter two share a common transcript that different from miR-34a [6]. MiR-34 family is ecognized as classic tumor suppressors due to their interaction with p53. Many studies have reported that miR-34 genes may be the potent mediators of tumor suppression by p53 because it can act as a transcription factor to regulate miR-34 expression by acting on the cis-acting element region of miR-34 [7]. EGFR affects numerous systems involved in oncogenesis and it has been proved as a direct target of miR-34a. Up regulation of miR-34a in xenografts will suppress tumor growth [8]. Similarly, the miR-183 cluster, which is comprised of miR-183, miR-96 and miR−182, is a miRNA family that also closely associated with tumorigenesis [9]. MiR-183-5p is required for NSCLC progression and enormously promotes cell proliferation, migration and cell cycle of NSCLC at the cellular level [10]. All these results indicate that microRNA clusters are of great significance in the treatment of tumor.

Of course, these miRNA clusters not only affect tumorigenesis, but also other metabolic diseases. MiR-34 family has been shown to play an important role in the wound healing, neural development, cell differentiation and so on. MiR-183 cluster also affects immune system, organ development, memory formation, etc. We believe that noncoding RNA clusters are promising to have a fundamental impact on the treatment of cancer.

REFERENCES

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10. Wang, H., et al., MiR-183-5p is required for non-small cell lung cancer progression by repressing PTEN. Biomed Pharmacother, 2019. 111: p. 1103-1111.

PEER REVIEW

Not commissioned. Externally peer reviewed.

References