期刊
RNA BIOLOGY
卷 12, 期 8, 页码 810-823出版社
TAYLOR & FRANCIS INC
DOI: 10.1080/15476286.2015.1056975
关键词
cancer; extracellular RNA; malignant melanoma; membrane vesicles; non-coding RNA; next-generation sequencing
资金
- Swedish Research Council [K2014-85x-22504-01-3, K2011-56K-20676-04-6]
- VBG Group Herman Krefting Foundation for Asthma and Allergy Research [20131212, 20121218]
- Swedish Heart and Lung Foundation [20120528]
- Swedish Cancer Foundation - CAN [2012/690]
- National Health Medical Research Council of Australia [628946]
- Australian Research Council [ARC] [FT100100560]
- Swedish Cancer Society
- Sahlgrenska Academy
- BioCARE - a National Strategic Cancer Research Program at University of Gothenburg
- Assar Gabrielsson's Foundation
- W.M. Lundgren's Foundation
- National Research Foundation of Korea [21A20131212415, 2011-0001760] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Melanoma cells release different types of extracellular vesicles (EVs) into the extracellular milieu that are involved with communication and signaling in the tumor microenvironment. Subsets of EVs include exosomes, microvesicles, and apoptotic bodies that carry protein and genetic (RNA) cargos. To define the contribution of the RNA cargo of melanoma cell derived EVs we performed small RNA sequencing to identify different small RNAs in the EV subsets. Using validated centrifugation protocols, we separated these EV subsets released by the melanoma cell line MML-1, and performed RNA sequencing with the Ion Torrent platform. Various, but different, non-coding RNAs were detected in the EV subsets, including microRNA, mitochondrial associated tRNA, small nucleolar RNA, small nuclear RNA, Ro associated Y-RNA, vault RNA and Y-RNA. We identified in total 1041 miRNAs in cells and EV subsets. Hierarchical clustering showed enrichment of specific miRNAs in exosomes, including hsa-miR-214-3p, hsa-miR-199a-3p and hsa-miR-155-5p, all being associated with melanoma progression. Comparison of exosomal miRNAs with miRNAs in clinical melanoma samples indicate that multiple miRNAs in exosomes also are expressed specifically in melanoma tissues, but not in benign naevi. This study shows for the first time the presence of distinct small RNAs in subsets of EVs released by melanoma cells, with significant similarities to clinical melanoma tissue, and provides unique insights into the contribution of EV associated extracellular RNA in cancer.
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