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

Abstract

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.

Epigenetic Factors and ncRNAs in Testicular Cancer

“…The expression of miRNAs has also been shown to be key in hallmarks of testicular cancer cells such as proliferation, apoptosis, and differentiation, correlated with clinical stage and tumor volume [127][128][129][130][131]. Other deregulated miRNAs have been found in non-SEM tumors and in advanced stages of TGCT.…”

Breaking the Mold: Epigenetics and Genomics Approaches Addressing Novel Treatments and Chemoresponse in TGCT Patients

“…Both molecules regulate fundamental cellular processes, and their abnormal expression is critical to the pathogenesis of human disease; they represent promising non-invasive serum biomarkers and therapeutic targets. The general roles of miRNAs and lncRNAs in testicular cancer have started to be understood [131,132].…”

miRNA in Molecular Diagnostics

“…The main deregulated miRNAs are miR199-214, influencing tumor metabolism through epigenetic regulators, miR371-373 influencing p53 pathway, cell cycle regulation, Wnt/β-catenin signaling, and senescence; and miR223, influencing apoptosis and cell growth through FBXW7 [ 152 , 154 , 155 , 159 , 160 ]. Other miRNA targets are cell cycle regulators, members of the p53 pathway involved in apoptosis regulation, DNA damage sensitivity, cell differentiation, and lactate metabolism [ 154 , 158 , 219 , 220 ].…”