دورية أكاديمية
MiR-200a Regulates CDK4/6 Inhibitor Effect by Targeting CDK6 in Metastatic Melanoma.
| العنوان: | MiR-200a Regulates CDK4/6 Inhibitor Effect by Targeting CDK6 in Metastatic Melanoma. |
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| المؤلفون: | Bustos, Matias, Ono, Shigeshi, Marzese, Diego M, Oyama, Takashi, Iida, Yuuki, Cheung, Garrett, Nelson, Nellie, Hsu, Sandy C, Yu, Qiang, Hoon, Dave S B |
| المصدر: | Articles, Abstracts, and Reports |
| بيانات النشر: | Providence St. Joseph Health Digital Commons |
| سنة النشر: | 2017 |
| المجموعة: | Providence St. Joseph Health Digital Commons |
| مصطلحات موضوعية: | Biopsy, Needle, Cell Cycle, Cell Proliferation, Cyclin-Dependent Kinase 4, Cyclin-Dependent Kinase 6, DNA Methylation, Disease Progression, Down-Regulation, Epigenomics, Gene Expression Regulation, Neoplastic, Humans, Immunohistochemistry, Melanoma, MicroRNAs, Neoplasm Metastasis, Sequence Analysis, RNA, Signal Transduction, Skin Neoplasms, Tumor Cells, Cultured, Dermatology, Oncology |
| الوصف: | The CDK4/6 pathway is frequently dysregulated in cutaneous melanoma. Recently, CDK4/6 inhibitors have shown promising clinical activity against several cancer types, including melanoma. Here, we show that microRNA-200a decreases CDK6 expression and thus reduces the response of CDK4/6 inhibitor in highly proliferative metastatic melanoma. Down-regulation of microRNA-200a expression in melanoma cells is associated with disease progression and a higher number of lymph node metastases. Furthermore, microRNA-200a expression is epigenetically modulated by both DNA methylation at the promoter region and chromatin accessibility of an upstream genomic region with enhancer activity. Mechanistically, overexpression of miR-200a in metastatic melanoma cells induces cell cycle arrest by targeting CDK6 and decreases the levels of phosphorylated-Rb1 and E2F-downstream targets, diminishing cell proliferation; these effects are recovered by CDK6 overexpression. Conversely, low microRNA-200a expression in metastatic melanoma cells results in higher levels of CDK6 and a more significant response to CDK4/6 inhibitors. We propose that microRNA-200a functions as a "cell cycle brake" that is lost during melanoma progression to metastasis and provides the ability to identify melanomas that are highly proliferative and more prompted to respond to CDK4/6 inhibitors. |
| نوع الوثيقة: | text |
| اللغة: | unknown |
| العلاقة: | https://digitalcommons.psjhealth.org/publications/1376Test; https://www.ncbi.nlm.nih.gov/pubmed/28526299Test |
| الإتاحة: | https://digitalcommons.psjhealth.org/publications/1376Test https://www.ncbi.nlm.nih.gov/pubmed/28526299Test |
| رقم الانضمام: | edsbas.85C51D39 |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |