Abstract 6687: Micromanaging resistance: microRNA expression and chemoresistance in testicular germ cell tumors

Abstract Testicular germ cell tumors (TGCTs) are the most common type of cancer among young men, and incidence has increased over the past 40 years. Approximately 80% of patients with metastatic TGCTs can be cured with chemotherapy; however, those patients that develop resistance to treatment often have a poor prognosis. Despite efforts to identify clear genetic factors that determine chemotherapy sensitivity and resistance in TGCTs, recent research has shifted focus toward the role of epigenetics in maintaining sensitivity to drugs like cisplatin and decitabine. Epigenetic mechanisms, including DNA methylation, histone modifications, and microRNAs (miRNAs), play a crucial role in regulating gene expression. Prior studies in somatic cancers have linked differential expressions of miRNAs to drug resistance. In this study, we hypothesized that the response of TGCTs to cisplatin and decitabine is partially influenced by miRNA expression. Through miRNA sequencing analysis followed by RT-qPCR validation, we identified distinct patterns of miRNA expression that correlate with resistance to cisplatin and decitabine in TGCTs. Consistent with our previous findings on protein coding gene expression, we observed that 54 miRNAs were reciprocally expressed between cells resistant to decitabine and those resistant to cisplatin. In follow-up analysis, we selected a subset of these reciprocally regulated miRNAs and predicted their target genes using miRDB and TargetScan. Downstream miRNA-RNA interactive analysis, enrichment analysis, and validation assays are ongoing and will be presented. Together, our study aims to elucidate the mechanistic roles of miRNAs in chemosensitivity and chemoresistance in TGCTs. The findings from this study will also support precise diagnosis and personalized treatment strategies for patients with TGCTs. Citation Format: Ratnakar Singh, Kelly Kries, Aayush Gupta, Amy Li, Zeeshan Fazal, Doha Shokry, Raya Boyd, Brayden Rennels, Sarah J. Freemantle, Michael J. Spinella. Micromanaging resistance: microRNA expression and chemoresistance in testicular germ cell tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 6687.