Anti-BCLAF1 monoclonal antibody, clone FQS0091(3)

The development of hepatocellular carcinomas (HCC) depends on their local microenvironment and the induction of neovascularization is a decisive step in tumor progression, since the growth of solid tumors is limited by nutrient and oxygen supply. Hypoxia is the critical factor that induces transcription of the hypoxia inducible factor-1 alpha (HIF-1 alpha) encoding gene HIF1A and HIF-1 alpha protein accumulation to promote angiogenesis. However, the basis for the transcriptional regulation of HIF1A expression in HCC is still unclear. Here, we show that Bcalf1 levels are highly correlated with HIF-1 alpha levels in HCC tissues, and that knockdown of Bcalf1 in HCC cell lines significantly reduces hypoxia-induced HIF1A expression. Furthermore, we found that Bcalf1 promotes HIF1A transcription via its bZIP domain, leading subsequently to increased transcription of the HIF-1 alpha downstream targets VEGFA, TGFB, and EPO that in turn promote HCC-associated angiogenesis and thus survival and thriving of HCC cells. Moreover, we demonstrate that HIF-alpha levels and microvessel density decrease after the shRNA-mediated Bcalf1 knockdown in xenograft tumors. Finally, we found that Bcalf1 levels increase in hypoxia in a HIF-1 alpha dependent manner. Therefore, our study identifies Bcalf1 as a novel positive regulator of HIF-1 alpha in the hypoxic microenvironment, providing new incentives for promoting Bcalf1 as a potential therapeutic target for an anti-HCC strategy.

Irritable bowel syndrome (IBS) is a common functional gastrointestinal (GI) disorder around world with no standard therapy. Till date, the pathophysiology of IBS is not clearly understood due to complexity of the disease. Current study reveals the underlying mechanism of IBS using systems biological approach. The complexity of IBS was explained by constructing protein-protein interaction (PPI) network from the text mined genes/proteins. PPI network displayed 68822 interactions from 3595 proteins. IBS interactome was mapped with colon tissue interactome which resulted in a sub-network containing 153 genes. Further, MCL algorithm was applied to sub-network to identify six major clusters. These cluster genes are involved in several pathways such as MAPK, PI3K/Akt, and NF-kappa B. The obtained clustered genes were prioritized using differentially expressed transcriptome data of 45 IBS and 45 normal volunteers. Among the differentially expressed genes, FUS, UNC5CL and BCLAF1 were found in the clusters, suggesting that the identified clusters could play a potential role in the regulation of IBS. Further pathway analysis of cluster genes revealed their molecular association with IBS. Gene prioritization studies identified top 10 genes that can be used as candidate biomarkers for early diagnosis of IBS. Out of top ten genes, PRPF31 was expressed in all biofluids (serum, saliva and urine).