Abstract Breast cancer (BC) is the leading cause of death by this disease in women worldwide. Among the factors involved in tumorigenesis, long non-coding RNAs (lncRNAs) and their differential expression have been associated. Differences in gene expression may be triggered by variations in DNA sequence, including single nucleotide polymorphisms (SNPs). In the present study, we analyzed the rs527616 (C>G), located in the lncRNA AQP4-AS1, using PCR-SSP in 306 BC patients and 312 controls, from a Brazilian population. In the BC group, the frequency found for CG heterozygotes was above the expected and the overdominant model is the best one to explain our results (OR: 1.70, IC 95%: 1.23-2.34, P<0.001). Furthermore, the SNP were associated with age at BC diagnosis and the risk genotype more frequent in the older age group. According to TCGA data, AQP4-AS1 is down-regulated in BC tissue, and the overexpression is associated with better prognoses, including Luminal A, HER2-, stage 1 of disease and smaller tumor. In conclusion, the CG genotype is associated with increased susceptibility in the southern Brazilian population. This SNP is mapped in the lncRNA AQP4-AS1, showing differential expression in BC samples. Based on these results, we emphasize the potential of the role of AQP4-AS1 in cancer.

Abstract Breast cancer (BC) is a heterogeneous disease, and it is the leading cause of death among women. NORAD and HCG11 are highly similar lncRNAs that present binding sites for PUMILIO proteins. PUMILIO acts on hundreds of mRNA targets, contributing to the modulation of gene expression. We analyzed the expression levels of NORAD and HCG11 in the BC subtypes luminal A (LA) and basal-like (BL), and the regulatory networks associated with these lncRNAs. In the analysis of TCGA cohort (n=329) and Brazilian BC samples (n=44), NORAD was up-regulated in LA while HCG11 was up-regulated in BL subtype. An increased expression of NORAD is associated with reduced disease-free survival in basal-like patients (p = 0.002), which suggests that its prognostic value could be different in specific subtypes. The biological pathways observed for the HCG11 network are linked to the epithelial-to-mesenchymal transition; while NORAD associated pathways appear to be related to luminal epithelial cell transformation. NORAD and HCG11 regulons respectively present 36% and 21.5% of PUMILIO targets, which suggests that these lncRNAs act as a decoy for PUMILIO. These lncRNAs seem to work as players in the differentiation process that drives breast cells to acquire distinct phenotypes related to a specific BC subtype.

Abstract MicroRNAs (miRNAs) play an essential role in gene expression and affect the development of tumours, including breast cancer (BC). Polymorphisms in miRNA genes can affect the interaction of miRNAs with their target messenger RNA by interfering, creating or disrupting target sites. The single nucleotide polymorphism (SNP) rs2910164, located in the seed region of miR146a, was shown to be associated with BC among different populations. In the present study, we investigated whether rs2910164 is associated with BC in 326 patients and 411 controls from a Brazilian population of predominantly European ancestry. The presence of the allele rs2910164*C was associated with an increased risk of BC (OR=1.4, 95% CI=1.03-1.85, p = 0.03). We also analysed publicly available RNA-seq data to evaluate if miR146a is differentially expressed in different subtypes of BC. Genotyping was performed by polymerase chain reaction with sequence-specific primers (PCR-SSP). By leveraging public data from TCGA database, we analysed 461 patients and found that miR146a is significantly more expressed in BC than in non-tumor tissue (1.47 fold, p = 0.02) and is expressed to a greater degree in aggressive BC subtypes.

O objetivo deste trabalho foi avaliar a qualidade pós-colheita de pêssegos da cultivar 'Aurora-1' enxertada sobre quatro porta-enxertos: 'Okinawa' propagado por sementes e por estacas herbáceas, Clone 15 e cv. Rigitano de umezeiro propagados por estacas herbáceas, e conduzidos em três espaçamentos: 6 x 2 m, 6 x 3 m e 6 x 4 m. Os frutos foram colhidos na safra de 2005, obedecendo ao estádio de maturação correspondente à coloração exigida para a comercialização in natura, eliminando-se os defeituosos, machucados ou fora do padrão de maturação estipulado. Foram realizadas análises físicas (massa fresca do fruto, diâmetro longitudinal, diâmetro equatorial, coloração externa, coloração interna e firmeza) e químicas dos frutos (sólidos solúveis, acidez titulável e índice de maturação). Os porta-enxertos e os espaçamentos estudados não influenciaram na coloração externa, no ângulo de cor e na luminosidade do mesocarpo, na firmeza e na acidez dos pêssegos 'Aurora-1'. Pêssegos 'Aurora-1' apresentaram maior massa fresca, diâmetro longitudinal e diâmetro equatorial, quando produzidos no Clone 15 e na cv. Rigitano de umezeiro como porta-enxerto. O uso do Clone 15 de umezeiro como porta-enxerto induziu à produção de frutos com maior teor de sólidos solúveis e melhor índice de maturação (gosto), em relação ao 'Okinawa' propagado por estacas herbáceas. O maior espaçamento entre plantas (6 x 4 m) induziu à produção de pêssegos menores, entretanto com maior teor de sólidos solúveis e melhor relação SS/AT.

The objective this research was to evaluate the post harvest 'Aurora-1' peaches quality, budded on four rootstocks ('Okinawa' propagated by seeds and herbaceous cuttings, Clone 15 and 'Rigitano' mume propagated by herbaceous cuttings), cultivated in three spacing: 6 x 2 m, 6 x 3 m and 6 x 4 m. Fruits harvest was realized in 2005, based on peel colors, which is the demand for in natura commercialization, corresponding to the maturation indexes. Fruit physical attributes like fruit fresh weight, longitudinal and equatorial diameter, firmness, external and internal color and chemical evaluations (soluble solids, acidity contents and ratio) were analyzed. Through the obtained data, it was verified that rootstocks and tree spacing did not influence the external color, hue and internal lightness mesocarp, the firmness and acidity contents of 'Aurora-1' peaches. The highest fruit fresh weight, longitudinal and equatorial diameters were obtained on Clone 15 and 'Rigitano' mume rootstock. 'Aurora-1' peach trees budded on Clone 15 mume rootstocks have got the highest soluble solids contents and ratio than 'Okinawa' propagated by herbaceous cuttings. 'Aurora-1' peach trees cultivated in 6 x 4 m space produced shorter fruits, but with the highest soluble solids contents and ratio.