Gene
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Computational analysis of biomolecular interaction networks is now gaining a lot of importance to understand the functions of novel genes/proteins. Gene interaction (GI) network analysis and protein-protein interaction (PPI) network analysis play a major role in predicting the functionality of interacting genes or proteins and gives an insight into the functional relationships and evolutionary conservation of interactions among the genes. ⋯ Also, various network analysis approaches like topological approach and clustering approach to study the network properties and functional enrichment server which illustrates the functions and pathway of the genes and proteins has been discussed. Hence the distinctive attribute mentioned in this review is not only to provide an overview of tools and web servers for gene and protein-protein interaction (PPI) network analysis but also to extract useful and meaningful information from the interaction networks.
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Germline mutations in the novel tumor suppressor gene FLCN are responsible for the autosomal dominant inherited disorder Birt-Hogg-Dubé (BHD) syndrome that predisposes to fibrofolliculomas, lung cysts and spontaneous pneumothorax, and an increased risk for developing kidney tumors. Although the encoded protein, folliculin (FLCN), has no sequence homology to known functional domains, x-ray crystallographic studies have shown that the C-terminus of FLCN has structural similarity to DENN (differentially expressed in normal cells and neoplasia) domain proteins that act as guanine nucleotide exchange factors (GEFs) for small Rab GTPases. ⋯ This review summarizes FLCN functional studies which support a role for FLCN in diverse metabolic pathways and cellular processes that include modulation of the mTOR pathway, regulation of PGC1α and mitochondrial biogenesis, cell-cell adhesion and RhoA signaling, control of TFE3/TFEB transcriptional activity, amino acid-dependent activation of mTORC1 on lysosomes through Rag GTPases, and regulation of autophagy. Ongoing research efforts are focused on clarifying the primary FLCN-associated pathway(s) that drives the development of fibrofolliculomas, lung cysts and kidney tumors in BHD patients carrying germline FLCN mutations.
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Comparative Study
Comparison of the role of HHIP SNPs in susceptibility to chronic obstructive pulmonary disease between Chinese Han and Mongolian populations.
The contribution of risk alleles to chronic obstructive pulmonary disease (COPD) may vary between populations. This study aimed to investigate the role of single nucleotide polymorphisms (SNPs) in HHIP on COPD susceptibility in the Chinese Mongolian and Han populations from Inner Mongolia autonomous region. In this case-control study, five SNPs in HHIP gene were detected in 700 COPD patients (350 Chinese Han and 350 Chinese Mongolian) and 700 healthy controls (350 Chinese Han and 350 Chinese Mongolian). ⋯ For the minor allele distribution, the differences between the Han and Mongolian were presented only in the case group for rs12504628 (P=0.003), rs13147758 (P=0.002), rs1828591 (P=0.001), and rs13118928 (P=0.002); for the genotypes, differences was presented at the frequency of the minor allele homozygote in rs13147758 (P=0.048), rs10519717 (P=0.027), rs1828591 (P=0.041), and rs13118928 (P=0.044) in Mongolian. Our findings suggested that HHIP rs10519717 might be associated with susceptibility of Mongolian COPD. For the other SNPs, the differences between the two populations were represented by minor allele distribution and frequency of the minor allele homozygotes.
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Liver fibrosis, characterized with the excessive accumulation of extracellular matrix (ECM) proteins, represents the final common pathway of chronic liver inflammation. Ever-increasing evidence indicates microRNAs (miRNAs) dysregulation has important implications in the different stages of liver fibrosis. However, our knowledge of miRNA-gene regulation details pertaining to such disease remains unclear. ⋯ Our integrated analysis of miRNA and gene expression profiles highlighted a functional miRNA-gene regulatory module associated with liver fibrosis, which, to some extent, may provide important clues to better understand the underlying pathogenesis of liver fibrosis.
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Abnormal activation of hepatic gluconeogenesis is a major contributor to fasting hyperglycemia in type 2 diabetes; however, the potential role of microRNAs in gluconeogenesis remains unclear. Here, we showed that hepatic expression levels of microRNA-21 (miR-21) were decreased in db/db and high-fat diet (HFD)-induced diabetic mice. Adenovirus-mediated overexpression of miR-21 decreased the expression of phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) and inhibited glucose production in primary mouse hepatocytes. ⋯ By contrast, silencing of miR-21 increased the protein levels of FOXO1, subsequently leading to a decrease in insulin sensitivity and impaired glucose intolerance in C57BL/6 mice fed with high-fat diet for 4weeks. Finally, we confirmed that FOXO1 was a potential target of miR-21. These results suggest that miR-21 is a critical regulator in hepatic gluconeogenesis and may provide a novel therapeutic target for treating insulin resistance and type 2 diabetes.