The New Tumour Biomarker miRNA-371-3p Influences Cisplatin Sensitivity of Testicular Germ Cell Tumour Cell Lines

Cisplatin is used to treat a variety of malignancies, including testicular germ cell tumours (TGCTs). Although cisplatin-­based chemotherapy yields high response rates, a subset of patients develop cisplatin resistance, limiting treatment options and worsening prognosis. Therefore, there is a high clinical need for new therapeutic strategies targeting cisplatin-­ resistant TGCTs. MicroRNA-­371a-­3p (miR-­ 371), the new serum biomarker for TGCTs, shows significantly increased expression in cisplatin-resistant TGCT cell lines compared to sensitive parental cell lines. However, the functional impact of miR-­371 on cisplatin sensitivity has not been investigated yet. To evaluate the impact of miR-­371 on cisplatin sensitivity, antagomirs were used to inhibit miR-­371 expression, resulting in a > 98 % decrease in miR-­371 expression. Cisplatin sensitivity was significantly increased after miR-­371 inhibition in cisplatin-­ resistant and corresponding parental TGCT cell lines, indicating a strongly reduced viability and increased apoptosis after cisplatin treatment in miR-­371-inhibited cells. Our results suggest that miR-­371 may contribute to the development of cisplatin resistance in TGCTs. Interfering with miR-­371 expression can increase the cisplatin sensitivity of tumor cells, which may represent a promising approach to improve future therapeutic outcomes in patients with TGCTs, especially those with cisplatin-­ resistant disease.