Identification of Key Genes in Angiogenesis of Breast and Prostate Cancers in the Context of Different Cell Types.

INTRODUCTION: Angiogenesis involves the development of new blood vessels. Biochemical signals start this process in the body, which is followed by migration, growth, and differentiation of endothelial cells that line the inside wall of blood vessels. This process is vital for the growth of cancer cells and tumors. MATERIALS AND METHODS: We started our analysis by composing a list of genes that have a validated impact in humans with respect to angiogenesis-related phenotypes. Here, we have investigated the expression patterns of angiogenesis-related genes in the context of previously published single-cell RNA-Seq data from prostate and breast cancer samples. RESULTS: Using a protein-protein interaction network, we showed how different modules of angiogenesis-related genes are overexpressed in different cell types. In our results, genes, such as ACKR1, AQP1, and EGR1, showed a strong cell type-dependent overexpression pattern in the two investigated cancer types, which can potentially be helpful in the diagnosis and follow-up of patients with prostate and breast cancer. CONCLUSION: Our work demonstrates how different biological processes in distinct cell types contribute to the angiogenesis process, which can provide clues regarding the potential application of targeted inhibition of the angiogenesis process.

The influence of the BCL11A polymorphism on the phenotype of patients with beta thalassemia could be affected by the beta globin locus control region and/or the Xmn1-HBG2 genotypic background.

To study the influence of the ß globin locus control region (LCR) genotypic background on the phenotype modifying role of BCL11A polymorphisms, 100 cases of thalassemia, 48 homozygous for the A allele and 52 homozygous for the G allele at the 5'HS4-LCR palindromic polymorphic site were genotyped for two BCL11A single nucleotide polymorphisms (rs11886868 and rs766432) in the intronic region of this gene. The effect of these polymorphisms on HbF variation was also examined in 122 normal individuals. The 5'HS4-LCR had the most significant role in determining the phenotype of these thalassemia patients. BCL11A polymorphisms showed a significant role in determining the phenotype of patients homozygous for the G allele at 5'HS4-LCR. However, the majority of patients homozygous for the A allele at 5'HS4-LCR, showed a severe phenotype, regardless of the BCL11A genotype. These results, without undermining the strength of BCL11A as a silencer of the γ globin gene, suggest that the LCR background, by governing the state of BCL11A binding to this region, plays a more significant role in determining the thalassemia phenotype than the level of BCL11A protein expression, that might be influenced by single nucleotide polymorphisms in intronic regions of the BCL11A gene. Functional studies to confirm the interactions between BCL11A and LCR could be useful in designing pharmacogenetic strategies for the treatment of beta thalassemia major.