Identification of MicroRNA–mRNA Networks in Melanoma and Their Association with PD-1 Checkpoint Blockade Outcomes
| العنوان: | Identification of MicroRNA–mRNA Networks in Melanoma and Their Association with PD-1 Checkpoint Blockade Outcomes |
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| المؤلفون: | Michael A. Davies, Miles C. Andrews, Russell G. Witt, Scott E. Woodman, Rodabe N. Amaria, Jeffrey E. Gershenwald, Khalida Wani, Lauren E. Haydu, Anik Banerjee, Chantale Bernatchez, Robert Sloane, Elizabeth M. Burton, Jennifer A. Wargo, Nadim J. Ajami, Jennifer L. McQuade, Emily Z. Keung, Julie M. Simon, Merrick I. Ross, Linghua Wang, Hussein Abdul-Hassan Tawbi, Michael G. White, Guangchun Han, Alexander J. Lazar |
| المصدر: | Cancers Volume 13 Issue 21 Cancers, Vol 13, Iss 5301, p 5301 (2021) |
| بيانات النشر: | Multidisciplinary Digital Publishing Institute, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Cancer Research, microRNA, business.industry, Melanoma, Cell, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, immune checkpoint blockade, Malignancy, medicine.disease, Article, Blockade, Transcriptome, medicine.anatomical_structure, Immune system, Oncology, Gene expression, medicine, Cancer research, melanoma, business, RC254-282 |
| الوصف: | Simple Summary We conducted a network analysis of microRNA–mRNA associations in melanoma tissue and cell lines to identify the microRNAs central to melanoma biology and their associated gene expression profiles. Further, we evaluated expression of these microRNAs in melanoma patient biopsies and found that increased expression of miR-100-5p and miR-125b-5p were associated with improved outcomes with anti-PD-1 immunotherapy. Further investigation of these microRNAs as biomarkers and potential targets to improve immunotherapy response in melanoma is warranted. Abstract Metastatic melanoma is a deadly malignancy with poor outcomes historically. Immuno-oncology (IO) agents, targeting immune checkpoint molecules such as cytotoxic T-lymphocyte associated protein-4 (CTLA-4) and programmed cell death-1 (PD-1), have revolutionized melanoma treatment and outcomes, achieving significant response rates and remarkable long-term survival. Despite these vast improvements, roughly half of melanoma patients do not achieve long-term clinical benefit from IO therapies and there is an urgent need to understand and mitigate mechanisms of resistance. MicroRNAs are key post-transcriptional regulators of gene expression that regulate many aspects of cancer biology, including immune evasion. We used network analysis to define two core microRNA–mRNA networks in melanoma tissues and cell lines corresponding to ‘MITF-low’ and ‘Keratin’ transcriptomic subsets of melanoma. We then evaluated expression of these core microRNAs in pre-PD-1-inhibitor-treated melanoma patients and observed that higher expression of miR-100-5p and miR-125b-5p were associated with significantly improved overall survival. These findings suggest that miR-100-5p and 125b-5p are potential markers of response to PD-1 inhibitors, and further evaluation of these microRNA–mRNA interactions may yield further insight into melanoma resistance to PD-1 inhibitors. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 2072-6694 |
| DOI: | 10.3390/cancers13215301 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e717d2c590f14613c6c19f09c0ec9412Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....e717d2c590f14613c6c19f09c0ec9412 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20726694 |
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| DOI: | 10.3390/cancers13215301 |