Recent Advances in Understanding the Biological Role of microRNA-371a-3p in Testicular Germ Cell Tumors

Testicular germ cell tumors (TGCTs) are the most common malignancies in young men. The clinical management largely relies on classical serum tumor markers. However, these markers offer limited sensitivity and specificity, underscoring the need for more reliable biomarkers. In recent years, members of the miR-371∼373 microRNA (miR) cluster, particularly miR-371a-3p, have emerged as superior alternatives, showing excellent diagnostic performance in various clinical settings. While most of the research efforts regarding miR-371∼373 have focused on its clinical utility, recent studies suggest that miR-371a-3p is more than just a diagnostic marker. In this narrative mini-review, we highlight five recent studies all of which provide novel insights into its broader biological roles. The key issues are as follows: (1) the release of miR-371a-3p from cancer cells is accomplished via extracellular vesicles; (2) the miRNA plays an important role in intercellular communication between tumor cells and the tumor microenvironment. (3) There are strong analogies between the human miR-371∼373 cluster and the murine miR-290∼295 cluster, which support the relevance of the gPAK mouse model for preclinical research. (4) miR-371a-3p contributes to cisplatin resistance in TGCTs, and antagomir-based inhibition of this miRNA might be an emerging potential therapeutic strategy. (5) The detection of miR-371a-3p in serum of pregnant women suggests a functional role in feto-maternal signaling. This concise review aims to bridge the gap between clinical and experimental research, positioning miR-371a-3p as both a superior biomarker and a pivotal molecule in TGCT biology with potential therapeutic implications.