Diverse Roles and Targets of miRNA in the Pathogenesis of Testicular Germ Cell Tumour.

Øyvind P Haugen,Trine B Haugen,Mrinal K Das

doi:10.3390/cancers14051190

Øyvind P Haugen, Trine B Haugen + Show 1 more

Open Access

https://doi.org/10.3390/cancers14051190

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Abstract

Simple SummaryTesticular germ cell tumour (TGCT) is the most common malignancy among young males in many parts of the world. Although it is highly remediable, treatments lead to long-term comorbidities, and therefore, it warrants a better prognosis. The presence of several risk loci in non-coding regions supports a functional role of miRNAs in TGCT development, and recent studies point to the emerging roles of miRNA and the complexity of miRNA-mediated gene regulation in TGCTs. miRNAs may act as oncogenes or tumour suppressors in TGCT by regulating targets involved in cell proliferation, apoptosis, and metastasis. Here, we summarise the gene regulation and function of miRNAs involved in TGCT pathogenesis.Testicular germ cell tumour (TGCT) is the most common cancer type among young adults in many parts of the world. Although the pathogenesis of TGCT is not well understood, the involvement of heritable components is evident, and the risk is polygenic. Genome-wide association studies have so far found 78 susceptibility loci for TGCT, and many of the loci are in non-coding regions indicating the involvement of non-coding RNAs in TGCT pathogenesis. MicroRNAs (miRNAs), a class of non-coding RNAs, have emerged as important gene regulators at the post-transcriptional level. They are crucial in controlling many cellular processes, such as proliferation, differentiation, and apoptosis, and an aberrant miRNA expression may contribute to the pathogenesis of several cancers, including TGCT. In support of this notion, several studies reported differential expression of miRNAs in TGCTs. We previously demonstrated that miRNAs were the most common group of small non-coding RNAs in TGCTs, and several functional studies of miRNAs in TGCTs suggest that they may act as either oncogene or tumour suppressors. Moreover, individual miRNA targets and downstream pathways in the context of TGCT development have been explored. In this review, we will focus on the diverse roles and targets of miRNAs in TGCT pathogenesis.

Highlights

Despite the rare incidence, testicular germ cell tumour (TGCT) is the most common cancer type among young men in many parts of the world [1]
It is believed that the foundation of TGCT happens with the developmental arrest of foetal gonocytes, followed by the development of the precursor cells called germ cell neoplasia in situ (GCNIS) [4]
The findings indicate an oncogenic role for these miRNAs in TGCT development

Summary

Introduction

Testicular germ cell tumour (TGCT) is the most common cancer type among young men in many parts of the world [1]. The inherited TGCT risk is largely polygenic [7], and genome-wide association studies have revealed 78 susceptibility loci for TGCT [8]. Functional studies show that a large part of the risk genes is related to male germ cell development, sex determination, and genomic integrity [9]. Several studies have reported the differential expression of miRNAs in TGCTs, subsequent functional studies of those miRNAs in TGCTs are few. This is partly due to the lack of suitable model systems for TGCT since there are differences in types and occurrence of testicular cancer between animals and humans [14,15]. We give a synopsis of functional miRNAs and their targets involved in TGCT pathogenesis

Male Germ Cell Development

Oncogenic Activity

Tumour Suppressor Activity

Conclusions