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The New Tumour Biomarker miRNA-371-3p Influences Cisplatin Sensitivity of Testicular Germ Cell Tumour Cell Lines
Richard Weiten1,2, Theadora Engler1, Hubert Schorle3
1Department of Urology and Paediatric Urology, University Hospital Bonn, Bonn, Germany.
Abstract:
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 tumour cells, which may represent a promising approach to improve future therapeutic outcomes in patients with TGCTs, especially those with cisplatin-resistant disease.
Insights
MicroRNA-371a-3p (miR-371) promotes cisplatin resistance in testicular germ cell tumors (TGCTs). Inhibiting miR-371 increases cisplatin sensitivity, offering a potential strategy for treating resistant TGCTs.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Cisplatin is a cornerstone chemotherapy for testicular germ cell tumors (TGCTs).
- Cisplatin resistance is a significant clinical challenge in TGCT treatment, necessitating novel therapeutic strategies.
- MicroRNA-371a-3p (miR-371) is a serum biomarker for TGCTs with elevated expression in cisplatin-resistant cell lines.
Purpose of the Study:
- To investigate the functional role of miR-371 in cisplatin sensitivity in TGCTs.
- To determine if inhibiting miR-371 can overcome cisplatin resistance in TGCT cell lines.
Main Methods:
- Utilized antagomirs to specifically inhibit miR-371 expression in TGCT cell lines.
- Quantified miR-371 expression levels post-inhibition (>98% decrease).
- Assessed cisplatin sensitivity by measuring cell viability and apoptosis after cisplatin treatment.
Main Results:
- Inhibition of miR-371 significantly enhanced cisplatin sensitivity in both cisplatin-resistant and sensitive TGCT cell lines.
- miR-371-inhibited cells exhibited reduced viability and increased apoptosis upon cisplatin exposure.
- These findings suggest miR-371 actively contributes to cisplatin resistance in TGCTs.
Conclusions:
- MicroRNA-371a-3p plays a role in the development of cisplatin resistance in TGCTs.
- Targeting miR-371 by inhibition represents a promising therapeutic approach to improve cisplatin efficacy in TGCT patients, particularly those with resistant disease.
