A Network of MicroRNAs and mRNAs Involved in Melanosome Maturation and Trafficking Defines the Lower Response of Pigmentable Melanoma Cells to Targeted Therapy
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Cell Culture
2.2. Drugs
2.3. Oligos
2.4. Generation of 501Mel Cells That Stably Express TYR-mCherry Fluorescent Protein
2.5. Transfection of miRNA Mimics and LNAs
2.6. Melanin Content Evaluation
2.7. Transmission Electron Microscope Analysis
2.8. Quantification of Released Melanosomes
2.9. Clonogenicity Assay
2.10. Co-Colture Assay
2.11. Xenograft in Zebrafish Embryos
2.12. RNA Extraction and Quantification
2.13. DNAse Treatment and Retrotranscription
2.14. Real-Time PCR
2.15. Protein Extraction and Western Blot Analysis
- -
- anti-DCT (#sc-74439, Santa Cruz Biotechnology, Dallas, TX, USA; mouse monoclonal antibody, dilution 1:1000 in 3% milk in TBST);
- -
- anti-GAPDH (#2118, Cell Signaling, Danvers, MA, USA; rabbit polyclonal antibody, dilution 1:3000 in 3% milk in TBST);
- -
- anti-PMEL17 (#sc-377325, Santa Cruz Biotechnology, Dallas, TX, USA; mouse monoclonal antibody, dilution 1:1000 in 3% milk in TBST);
- -
- anti-TYR (#sc-20035, Santa Cruz Biotechnology, Dallas, TX, USA; mouse monoclonal antibody, dilution 1:1000 in 3% milk in TBST);
- -
- anti-TYRP1 (#sc-166857, Santa Cruz Biotechnology, Dallas, TX, USA; mouse monoclonal antibody, dilution 1:1000 in 3% milk in TBST).
2.16. Statistical Analysis
2.17. Deep Sequencing
2.17.1. Sample Preparation
2.17.2. Library Generation and Sequencing
2.17.3. Primary Analysis, Clustering, and Differential Expression Analysis
2.18. clusterProfiler Analysis
2.19. WGCNA Analysis
2.19.1. Construction of Weighted Gene Co-Expression Network and Identification of Hub Modules
2.19.2. clusterProfiler Analysis of the Genes Belonging to WGCNA Modules
2.20. SWIMmeR Analysis
2.20.1. miRNAs-Module Association
2.20.2. Functional Enrichment Analysis
2.21. Gene Correlations Analysis
3. Results and Discussion
3.1. Identification of Differentially Expressed miRNAs and mRNAs in Pigmentable vs. Non-Pigmentable Cell Lines upon Vem Treatment
3.2. Identification of Biological Processes Selectively Enriched in Pigmentable vs. Non-Pigmentable Cell Lines upon Vem Treatment
3.2.1. Enriched Functional Profiles Analysis by clusterProfiler
3.2.2. Modules Analysis by WGCNA
3.2.3. Switch Genes Analysis by SWIMmeR
3.3. Validation of DEmiRs and DEmRNAs Identified by Bioinformatic Analyses
3.4. Validation of the Pigmentation-Related Biological Processes Identified by Bioinformatic Analyses
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Type | Gene | Sense (5′-3′) | Antisense (5′-3′) | PMID |
---|---|---|---|---|
qRT-PCR primers | ATPA1 | CTCAGATGTGTCCAAGCAAG | GTCAGTGCCCAAGTCAATG | 28445987 |
DCT | CCTTTCTTCCCTCCAGTGAC | AGCCAACAGCACAAAAAGAC | 28445987 | |
GAPDH | CGCTCTCTGCTCCTCCTGTT | CCATGGTGTCTGAGCGATGT | 28445987 | |
MITF | TGACCGCATTAAAGAACTAGG | GTGCTCCAGTTTCTTCTGTCG | 28445987 | |
MLANA | CTCTTACACCACGGCTGAA | AGACTCCCAGGATCACT | 28445987 | |
PBGD | TCCAAGCGGAGCCATGTCTG | AGAATCTTGTCCCCTGTGGTGGA | 28445987 | |
PGC1alpha | GTCACCACCCAAATCCTTAT | CGGTGTCTGTAGTGGCTTGA | 28445987 | |
SDHA | CCACTCGCTATTGCACACC | CACTCCCCATTCTCCATCA | 28445987 | |
TRPM1 | TGCGAAGGCTGCTGGAAA | CAAGACGATGGACACCACGTTAGG | 28445987 | |
TYR | GATGAGTACATGGGAGGTCAGC | GTACTCCTCCAATCGGCTACAG | 28445987 | |
TYRP1 | GGACCAGCTTTTCTCACAT | GAATCAAAGTTGCTTCTGGA | 28445987 | |
LNAs | LNA-CT | GTGTAACACGTCTATACGCCCA | 28445987 | |
LNA-211 | AGGCGAAGGATGACAAAGGGAA | 28445987 |
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Vitiello, M.; Mercatanti, A.; Podda, M.S.; Baldanzi, C.; Prantera, A.; Sarti, S.; Rizzo, M.; Salvetti, A.; Conte, F.; Fiscon, G.; et al. A Network of MicroRNAs and mRNAs Involved in Melanosome Maturation and Trafficking Defines the Lower Response of Pigmentable Melanoma Cells to Targeted Therapy. Cancers 2023, 15, 894. https://doi.org/10.3390/cancers15030894
Vitiello M, Mercatanti A, Podda MS, Baldanzi C, Prantera A, Sarti S, Rizzo M, Salvetti A, Conte F, Fiscon G, et al. A Network of MicroRNAs and mRNAs Involved in Melanosome Maturation and Trafficking Defines the Lower Response of Pigmentable Melanoma Cells to Targeted Therapy. Cancers. 2023; 15(3):894. https://doi.org/10.3390/cancers15030894
Chicago/Turabian StyleVitiello, Marianna, Alberto Mercatanti, Maurizio Salvatore Podda, Caterina Baldanzi, Antonella Prantera, Samanta Sarti, Milena Rizzo, Alessandra Salvetti, Federica Conte, Giulia Fiscon, and et al. 2023. "A Network of MicroRNAs and mRNAs Involved in Melanosome Maturation and Trafficking Defines the Lower Response of Pigmentable Melanoma Cells to Targeted Therapy" Cancers 15, no. 3: 894. https://doi.org/10.3390/cancers15030894
APA StyleVitiello, M., Mercatanti, A., Podda, M. S., Baldanzi, C., Prantera, A., Sarti, S., Rizzo, M., Salvetti, A., Conte, F., Fiscon, G., Paci, P., & Poliseno, L. (2023). A Network of MicroRNAs and mRNAs Involved in Melanosome Maturation and Trafficking Defines the Lower Response of Pigmentable Melanoma Cells to Targeted Therapy. Cancers, 15(3), 894. https://doi.org/10.3390/cancers15030894