Rabbit Anti-Human U2AF1 Polyclonal antibody

Background: Telomere erosion can lead to genomic instability and cancer progression. It has been suggested that the shortest telomere, not the average telomere length (TL), is critical for cell viability. Some studies have shown shorter TL in myelodysplastic syndrome (MDS) patients but the critically short telomeres, the variability of TL within individual patient has not been evaluated. Thus, we aimed to investigate the TL of MDS patients and assessed the association of TL with recurrent genetic mutations in MDS. Methods: We measured the TL of bone marrow nucleated cells for diagnostic samples at a single-cell level by quantitative fluorescence in situ hybridization (Q-FISH) for 58 MDS patients and analyzed the minimum, median, average, standard deviation, average of the 0th to 10th percentile TL within a patient, and the proportion of cells with TL that is shorter than the lowest 10th percentile of the normal control (NC). The correlations of TL to clinical parameters, cytogenetic results, and genetic mutations were assessed. Results: MDS patients showed eroded telomeres and narrow distribution compared to the NC (P < 0.001, P = 0.018, respectively). Patients with mutation showed significantly lesser cells with short TL, below the lowest 10th percentile of the NC (P = 0.017), but no differences in TL were found according to mutations/cytogenetic abnormalities except for CSF3R mutation. However, those patients with a high percentage (>= 80 %) of cells with short TL showed poorer overall survival (P = 0.021), and this was an independent prognostic factor, along with TP53, U2AF1 mutation, and high BM blast count (P = 0.044, 0.001, 0.004, 0.012, respectively). Conclusions: The shortest TL, which determines the fate of the cell, was significantly shorter, and higher burden of cells with short TL were found in MDS, which correlated with poor survival, suggesting the need to measure TL in single cells by Q-FISH.

Background: Colorectal cancer (CRC) is a major public health problem, being the leading causes of mortality and morbidity worldwide. Exosomes are crucial to the molecular pathogenesis of CRC. It is essential to investigate the key differentially expressed genes (DEGs) in CRC exosomes. Methods: The DEGs between CRC patients and normal participants were screened using microarray data downloaded from the Gene Expression Omnibus (GEO) and exoRBase database. Gene ontology (GO), pathway enrichment analysis, protein-protein interaction (PPI) network, module analysis, overall survival (OS) analysis of liub genes and functional annotation of DEGs were performed. Results: A total of 149 DEGs in CRC exosomes and 1,507 DEGs in CRC tissues were identified with selecting criteria of P value < 0.05. GO terms of positive regulation of gene expression, protein binding to Golgi, cellular protein metabolic process and endonuclease activity were significantly enriched in CRC exosomes. CRC exosomes were mainly enriched in pathways of RNA transport, alcoholism, viral carcinogenesis, spliceosome and Ras signaling pathway. We then selected UBC, H3F3A, HIST2H2AA3, AKT3, and HSPA1B as the hub protein in CRC exosomes according to the PPI network. OS analysis showed overexpression of HIST2H2AA3 was related to poor prognosis. Four oncogenes including H3F3A, U2AF1, P2RY8 and APOBEC3B were identified in the exosomes. There was no significant difference in the ratio of tumor suppressor genes (TSGs) to oncogenes between tumor tissues and exosomes according to functional annotation of DEGs. Conclusions: Hub genes including UBC, H3F3A, HIST2H2AA3, AKT3, and HSPA1B might serve as new diagnostic and therapeutic targets of CRC in the future.