A significant proportion of mammalian genomes corresponds to genes that transcribe long non-coding RNAs (lncRNAs). Throughout the last decade, the number of studies concerning the roles played by lncRNAs in different biological processes has increased considerably. This intense interest in lncRNAs has produced a major shift in our understanding of gene and genome regulation and structure. It became apparent that lncRNAs regulate gene expression through several mechanisms. These RNAs function as transcriptional or post-transcriptional regulators through binding to histone-modifying complexes, to DNA, to transcription factors and other DNA binding proteins, to RNA polymerase II, to mRNA, or through the modulation of microRNA or enzyme function. Often, the lncRNA transcription itself rather than the lncRNA product appears to be regulatory. In this review, we highlight studies identifying lncRNAs in the homeostasis of various cell and tissue types or demonstrating their effects in the expression of protein-coding or other non-coding RNA genes.

PurposeTriple-negative breast cancer (TNBC), an aggressive breast cancer subtype, is genetically heterogeneous which challenges the identification of clinically effective molecular makers. Extracellular vesicles (EVs) are key players in the intercellular signaling communication and have been shown to be involved in tumorigenesis. The main goal of this study was to evaluate the role and mechanisms of EVs derived from TNBC cells in modulating proliferation and cytotoxicity to chemotherapeutic agents in non-tumorigenic breast cells (MCF10A).MethodsEVs were isolated from TNBC cell lines and characterized by nanoparticle tracking analysis, Western blot, and transmission electron microscopy. MCF10A cells were treated with the isolated EVs and evaluated for cell proliferation and cytotoxicity to Docetaxel and Doxorubicin by the MTT and MTS assays, respectively. Gene and miRNA expression profiling was performed in the treated cells to determine expression changes that may be caused by EVs treatment.ResultsMCF10A cells treated with HCC1806-EVs (MCF10A/HCC1806-EVs) showed a significant increase in cell proliferation and resistance to the therapeutic agents tested. No significant effects were observed in the MCF10A cells treated with EVs derived from MDA-MB-231 cells. Gene and miRNA expression profiling revealed 138 genes and 70 miRNAs significantly differentially expressed among the MCF10A/HCC1806-EVs and the untreated MCF10A cells, affecting mostly the PI3K/AKT, MAPK, and HIF1A pathways.ConclusionEVs isolated from the HCC1806 TNBC cells are capable of inducing proliferation and drug resistance on the non-tumorigenic MCF10A breast cells, potentially mediated by changes in genes and miRNAs expression associated with cell proliferation, apoptosis, invasion, and migration.Electronic supplementary materialThe online version of this article (10.1007/s10549-018-4925-5) contains supplementary material, which is available to authorized users.

MicroRNAs derived from extracellular vesicles (EV-miRNAs) are circulating miRNAs considered as potential new diagnostic markers for cancer that can be easily detected in liquid biopsies. In this study, we performed RNA sequencing analysis as a screening strategy to identify EV-miRNAs derived from serum of clinically well-annotated breast cancer (BC) patients from the south of Brazil. EVs from three groups of samples (healthy controls (CT), luminal A (LA), and triple-negative (TNBC)) were isolated from serum using a precipitation method and analyzed by RNA-seq (screening phase). Subsequently, four EV-miRNAs (miR-142-5p, miR-150-5p, miR-320a, and miR-4433b-5p) were selected to be quantified by quantitative real-time PCR (RT-qPCR) in individual samples (test phase). A panel composed of miR-142-5p, miR-320a, and miR-4433b-5p distinguished BC patients from CT with an area under the curve (AUC) of 0.8387 (93.33% sensitivity, 68.75% specificity). The combination of miR-142-5p and miR-320a distinguished LA patients from CT with an AUC of 0.9410 (100% sensitivity, 93.80% specificity). Interestingly, decreased expression of miR-142-5p and miR-150-5p were significantly associated with more advanced tumor grades (grade III), while the decreased expression of miR-142-5p and miR-320a was associated with a larger tumor size. These results provide insights into the potential application of EVs-miRNAs from serum as novel specific markers for early diagnosis of BC.

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Following the candidate gene approach we analyzed the CD40L, CD40, BLYS and CD19 genes that participate of B-cell co-stimulation, for association with pemphigus foliaceus (PF), an organ-specific autoimmune disease, characterized by the detachment of epidermal cells from each other (acantholysis) and presence of autoantibodies specific for desmoglein 1 (dsg1), an epidermal cell-adhesion molecule. The disease is endemic in certain regions of Brazil and also is known as fogo selvagem. Complex interactions among environmental and genetic susceptibility factors contribute to the manifestation of this multifactorial disease. The sample included 179 patients and 317 controls. Strong significant association was found with CD40LÀ726T4C (odds ratio, OR ¼ 5.54 and 0.30 for T þ and C þ genotypes, respectively). In addition, there were significant negative associations with CD40 À1T (OR ¼ 0.61) and BLYSÀ871T (OR ¼ 0.62) due to the decrease of the frequency of both homo-and heterozygotes in the patient group. No associations were found with variants of CD19 gene. Gene-gene interactions were observed between CD40 and BLYS, and between CD40L and BLYS. So, the dominant protective effects of CD40LÀ726C and of CD40 À1T only manifest in BLYSÀ871T þ individuals, and vice versa. We conclude that genetic variability of CD40L, CD40 and BLYS is an important factor for PF pathogenesis.