title: Distinct Small RNA Signatures in Extracellular Vesicles Derived from Breast Cancer Cell Lines.
abstract: Breast cancer is a heterogeneous disease, and different subtypes of breast cancer show distinct cellular morphology, gene expression, metabolism, motility, proliferation, and metastatic potential. Understanding the molecular features responsible for this heterogeneity is important for correct diagnosis and better treatment strategies. Extracellular vesicles (EVs) and their associated molecules have gained much attention as players in intercellular communication, ability to precondition specific organs for metastatic invasion, and for their potential role as circulating cancer biomarkers. EVs are released from the cells and contain proteins, DNA, and long and small RNA species. Here we show by high-throughput small RNA-sequencing that EVs from nine different breast cancer cell lines share common characteristics in terms of small RNA content that are distinct from their originating cells. Most strikingly, a highly abundant small RNA molecule derived from the nuclear 28S rRNA is vastly enriched in EVs. The miRNA profiles in EVs correlate with the cellular miRNA expression pattern, but with a few exceptions that includes miR-21. This cancer-associated miRNA is retained in breast cancer cell lines. Finally, we report that EVs from breast cancer cell lines cluster together based on their small RNA signature when compared to EVs derived from other cancer cell lines. Altogether, our data demonstrate that breast cancer cell lines manifest a specific small RNA signature in their released EVs. This opens up for further evaluation of EVs as breast cancer biomarkers.
authors: Department of Medical Biology, Faculty of Health Sciences, UiT-The Arctic University of Norway, MH-building Breivika, Tromsø, N-9037, Norway.|Department of Pharmacy, Faculty of Health Sciences, UiT-The Arctic University of Norway, MH-building Breivika, Tromsø, N-9037, Norway.
authors: Tonje
authors: http://orcid.org/0000-0002-3906-8825
authors: T
authors: Fiskaa
authors: Department of Medical Biology, Faculty of Health Sciences, UiT-The Arctic University of Norway, MH-building Breivika, Tromsø, N-9037, Norway.
authors: Erik
authors: E
authors: Knutsen
authors: Department of Pharmacy, Faculty of Health Sciences, UiT-The Arctic University of Norway, MH-building Breivika, Tromsø, N-9037, Norway.
authors: Marlen Aas
authors: MA
authors: Nikolaisen
authors: Marine Genomics group, Faculty of Biosciences and Aquaculture, Nord University, Bodø, Norway.
authors: Tor Erik
authors: TE
authors: Jørgensen
authors: Department of Medical Biology, Faculty of Health Sciences, UiT-The Arctic University of Norway, MH-building Breivika, Tromsø, N-9037, Norway.|Marine Genomics group, Faculty of Biosciences and Aquaculture, Nord University, Bodø, Norway.
authors: Steinar Daae
authors: SD
authors: Johansen
authors: Department of Medical Biology, Faculty of Health Sciences, UiT-The Arctic University of Norway, MH-building Breivika, Tromsø, N-9037, Norway.
authors: Maria
authors: M
authors: Perander
authors: Department of Pharmacy, Faculty of Health Sciences, UiT-The Arctic University of Norway, MH-building Breivika, Tromsø, N-9037, Norway.
authors: Ole Morten
authors: OM
authors: Seternes
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics*; D045744:Cell Line, Tumor; D000067128:Extracellular Vesicles / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D015972:Gene Expression Regulation, Neoplastic; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods; D006801:Humans; D061986:MCF-7 Cells; D035683:MicroRNAs / Q000235:genetics; D012339:RNA, Ribosomal, 28S / Q000235:genetics; D058727:RNA, Small Untranslated / Q000235:genetics*; D017423:Sequence Analysis, RNA / Q000379:methods
chemical_list: D014408:Biomarkers, Tumor; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D012339:RNA, Ribosomal, 28S; D058727:RNA, Small Untranslated