Protein ubiquitination is a dynamic and reversible process of adding single ubiquitin molecules or various ubiquitin chains to target proteins. Here, using multidimensional omic data of 9,125 tumor samples across 33 cancer types from The... more
Protein ubiquitination is a dynamic and reversible process of adding single ubiquitin molecules or various ubiquitin chains to target proteins. Here, using multidimensional omic data of 9,125 tumor samples across 33 cancer types from The Cancer Genome Atlas, we perform comprehensive molecular characterization of 929 ubiquitin-related genes and 95 deubiquitinase genes. Among them, we systematically identify top somatic driver candidates, including mutated FBXW7 with cancer-type-specific patterns and amplified MDM2 showing a mutually exclusive pattern with BRAF mutations. Ubiquitin pathway genes tend to be upregulated in cancer mediated by diverse mechanisms. By integrating pan-cancer multiomic data, we identify a group of tumor samples that exhibit worse prognosis. These samples are consistently associated with the upregulation of cell-cycle and DNA repair pathways, characterized by mutated TP53, MYC/TERT amplification, and APC/PTEN deletion. Our analysis highlights the importance of...
Obesity has the far reaching consequence on cancer pathogenesis and immune reactions. In particular, adiponectin (APN) produced by adipocytes played an important role in modulating obesity related malignancies. Via its interaction with... more
Obesity has the far reaching consequence on cancer pathogenesis and immune reactions. In particular, adiponectin (APN) produced by adipocytes played an important role in modulating obesity related malignancies. Via its interaction with corresponding receptors and their downstream signalling pathways, it regulates cells survival, apoptosis and cancer metastasis. Our review dissects the clinical evidence on how hypoadiponectinaemia associated with the increased risks of several cancers and the long-term prognosis and also addresses the controversies. APN also has its indirect effect on anti-cancer immune response which may influence the disease process. We also analyse the impact of APN on the immune system, the anti-tumour responses and the controversies surrounding this area. Targeting therapeutics on APN and its receptor axis represents a promising and novel anti-cancer treatment. Biological understanding of how APN and its interaction with its receptors may affect the immune reactivity. Careful strategizing the use of APN therapeutics in cancer treatment is important, as the APN receptor signalling on the immune cells can blunt anti-tumour response. Targeting APN or its receptors has an enormous implication for the treatment of cancers.
The interferon regulatory factors (IRFs) are a family of master transcription factors that regulate pathogen-induced innate and acquired immune responses. Aberration(s) in IRF signaling pathways due to infection, genetic predisposition... more
The interferon regulatory factors (IRFs) are a family of master transcription factors that regulate pathogen-induced innate and acquired immune responses. Aberration(s) in IRF signaling pathways due to infection, genetic predisposition and/or mutation, which can lead to increased expression of type I interferon (IFN) genes, IFN-stimulated genes (ISGs), and other pro-inflammatory cytokines/chemokines, has been linked to the development of numerous diseases, including (but not limited to) autoimmune and cancer. What is currently lacking in the field is an understanding of how best to therapeutically target these transcription factors. Many IRFs are regulated by post-translational modifications downstream of pattern recognition receptors (PRRs) and some of these modifications lead to activation or inhibition. We and others have been able to utilize structural features of the IRFs in order to generate dominant negative mutants that inhibit function. Here, we will review potential therapeutic strategies for targeting all IRFs by using IRF5 as a candidate targeting molecule.
Sialic acids and MMPs play critical roles in inflammatory diseases. Furthermore, Interaction between Sialic acid and receptors such as siglecs leads phosphorylation of ITIM domains and promote downstream inhibitory signaling through SHP-1... more
Sialic acids and MMPs play critical roles in inflammatory diseases. Furthermore, Interaction between Sialic acid and receptors such as siglecs leads phosphorylation of ITIM domains and promote downstream inhibitory signaling through SHP-1 phosphatases. SHP1 could positively regulate TNF-α and by control, the production of TNF-α could play a crucial role in inflammation. Besides, TNF-α could mediate the signaling pathway leading to MMP-9 gene expression. MMP-9 also is recognized as therapeutic targets in a variety of diseases including vascular pathologies, cancers, and auto-immuned diseases. The present in-silico study aims to identify the most potent micro-RNAs could control the signaling pathway from siglec to MMP-9. To this end, with review some articles and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis 21 genes involved in this pathway have been selected. Then TARGET SCAN, DIANA-TarBase8, and miRDB database were utilized to predict the miRNAs which h...
Sialic acids and MMPs play critical roles in inflammatory diseases. Furthermore, Interaction between Sialic acid and receptors such as siglecs leads phosphorylation of ITIM domains and promote downstream inhibitory signaling through SHP-1... more
Sialic acids and MMPs play critical roles in inflammatory diseases. Furthermore, Interaction between Sialic acid and receptors such as siglecs leads phosphorylation of ITIM domains and promote downstream inhibitory signaling through SHP-1 phosphatases. SHP1 could positively regulate TNF-α and by control, the production of TNF-α could play a crucial role in inflammation. Besides, TNF-α could mediate the signaling pathway leading to MMP-9 gene expression. MMP-9 also is recognized as therapeutic targets in a variety of diseases including vascular pathologies, cancers, and auto-immuned diseases. The present in-silico study aims to identify the most potent micro-RNAs could control the signaling pathway from siglec to MMP-9. To this end, with review some articles and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis21 genes involved in this pathway have been selected. Then TARGET SCAN, DIANA-TarBase8, and miRDB database were utilized to predict the miRNAs which ha...
