Related Experiment Video
Updated: Aug 10, 2025
Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis
Published on: March 30, 2019
Integrated Microarray-Based Data Analysis of miRNA Expression Profiles: Identification of Novel Biomarkers of
Jan Roška1, João Lobo2,3,4, Danica Ivovič1
1Department of Genetics, Cancer Research Institute, Biomedical Research Center, Slovak Academy of Sciences, Dúbravská cesta 9, 845 05 Bratislava, Slovakia.
Abstract:
Testicular germ cell tumours (TGCTs) are the most common solid malignancy among young men, and their incidence is still increasing. Despite good curability with cisplatin (CDDP)-based chemotherapy, about 10% of TGCTs are non-responsive and show a chemoresistant phenotype. To further increase TGCT curability, better prediction of risk of relapse and early detection of refractory cases is needed. Therefore, to diagnose this malignancy more precisely, stratify patients more accurately and improve decision-making on treatment modality, new biomarkers are still required. Numerous studies showed association of differential expressions of microRNAs (miRNAs) with cancer. Using microarray analysis followed by RT-qPCR validation, we identified specific miRNA expression patterns that discriminate chemoresistant phenotypes in TGCTs. Comparing CDDP-resistant vs. -sensitive TGCT cell lines, we identified miR-218-5p, miR-31-5p, miR-125b-5p, miR-27b-3p, miR-199a-5p, miR-214-3p, let-7a and miR-517a-3p as significantly up-regulated and miR-374b-5p, miR-378a-3p, miR-20b-5p and miR-30e-3p as significantly down-regulated. In patient tumour samples, we observed the highest median values of relative expression of miR-218-5p, miR-31-5p, miR-375-5p and miR-517a-3p, but also miR-20b-5p and miR-378a-3p, in metastatic tumour samples when compared with primary tumour or control samples. In TGCT patient plasma samples, we detected increased expression of miR-218-5p, miR-31-5p, miR-517a-3p and miR-375-5p when compared to healthy individuals. We propose that miR-218-5p, miR-31-5p, miR-375-5p, miR-517-3p, miR-20b-5p and miR-378a-3p represent a new panel of biomarkers for better prediction of chemoresistance and more aggressive phenotypes potentially underlying metastatic spread in non-seminomatous TGCTs. In addition, we provide predictions of the targets and functional and regulatory networks of selected miRNAs.
Insights
Testicular germ cell tumours (TGCTs) are common in young men. New microRNA (miRNA) biomarkers can predict chemoresistance and metastasis in TGCT patients, improving treatment outcomes.
Area of Science:
- Oncology
- Molecular Biology
- Biomarker Discovery
Background:
- Testicular germ cell tumours (TGCTs) are the most common solid malignancy in young men, with increasing incidence.
- While cisplatin (CDDP)-based chemotherapy is effective, approximately 10% of TGCTs exhibit chemoresistance, necessitating improved prediction and early detection strategies.
- MicroRNAs (miRNAs) have emerged as potential biomarkers due to their association with various cancers.
Purpose of the Study:
- To identify specific miRNA expression patterns that can discriminate chemoresistant phenotypes in TGCTs.
- To discover novel biomarkers for predicting chemoresistance and aggressive disease progression in TGCTs.
- To investigate the potential of miRNAs as diagnostic and prognostic tools for TGCT management.
Main Methods:
- Microarray analysis was employed to identify differentially expressed miRNAs between CDDP-resistant and -sensitive TGCT cell lines.
- Reverse transcription quantitative polymerase chain reaction (RT-qPCR) was used for validation of selected miRNA candidates.
- miRNA expression levels were analyzed in patient tumor and plasma samples to correlate with clinical phenotypes and metastatic status.
Main Results:
- Specific miRNA expression patterns were identified, distinguishing chemoresistant TGCT phenotypes.
- Several miRNAs, including miR-218-5p, miR-31-5p, miR-125b-5p, and miR-517a-3p, were significantly up-regulated in chemoresistant cell lines.
- Elevated expression of miR-218-5p, miR-31-5p, miR-375-5p, miR-517a-3p, miR-20b-5p, and miR-378a-3p was observed in metastatic tumors and plasma samples from TGCT patients compared to controls.
Conclusions:
- A panel of miRNAs (miR-218-5p, miR-31-5p, miR-375-5p, miR-517-3p, miR-20b-5p, and miR-378a-3p) shows promise as biomarkers for predicting chemoresistance and aggressive phenotypes in non-seminomatous TGCTs.
- These miRNAs may aid in identifying patients at higher risk of metastatic spread.
- Further research into the functional roles and regulatory networks of these miRNAs could enhance TGCT treatment strategies.
More Related Videos
09:40Author Spotlight: Unveiling the Role of TMOD3 in Platinum Resistance and Immune Infiltration in Ovarian Cancer
Published on: August 2, 2024
09:40Characterization of Functionally Associated miRNAs in Glioblastoma and their Engineering into Artificial Clusters for Gene Therapy
Published on: October 4, 2019