Abstract:Multivesicular body (MVB) is a dynamic subcellular organelle formed by invagination of the limiting membrane of late endosome. MVB is an essential transport and sorting station for membranes and proteins in eukaryotic organisms. MVB pathway is intimately involved in various processes, including signal transduction, cytokinesis, gene silencing, autophagy, protein quality control and virus budding. The biogenesis of MVB requires more than 20 vacuolar protein sorting (Vps) proteins. Many of them can assemble into four distinct complexes ESCRT 0,Ⅰ,Ⅱ,Ⅲ (endosomal sorting complexs required for transport) on the endosomal membrane. ESCRTs and Vps4 are considered to be the most important components in MVB pathway. ESCRT 0 together with clathrin can form microdomain on endosomal membrane where they cluster ubiquitinated cargo proteins. ESCRTⅠ and Ⅱ can induce the budding of intraluminal vesicles (ILVs), prompt the formation process and sort protein cargoes into ILVs. ESCRTⅢ can constrict, cleave the bud neck and finish the membrane abscission, the last stage of MVB formation. Vps4 can disassemble ESCRT complexes and recycle them. Ubiquitinated cargo proteins and ubiquitination can also regulate the localization and function of ESCRTs. Together, these recent discoveries demonstrate that the sequential and co-ordinated actions of ubiquitinated cargo proteins, ESCRTs and Vps4 are the major driving force for the biogenesis of MVB and protein sorting process. In this review, we focus on the protein-protein interaction and mainly discuss the assembly mechanism, interaction and function of ESCRT complexes and Vps4 high-order oligomers, as well as the regulation of ESCRTs by ubiquitinated proteins and ubiquitination. We also suggest prospective studies based on these discussions.

Abstract:This article overviewed the study progression of the roles of a class of non-coding RNAs termed microRNAs on lipid metabolism and the effects of fatty acids on microRNA expression. miRNAs can regulate lipid metabolism in multiple levels. miR-122, -307, -33 and so on can regulate fatty acid synthesis, fatty acid oxidation, triglyceride synthesis, cholesterol flow and lipoprotein synthesis in direct or indirect ways via the combination to their target genes. Lipids of diets, especially the essential fatty acids, can involve in the biology processes, such as cancer resistance and inflammation remission, via the regulation of miRNAs.

Abstract:Lysine acetylation can be defined as the transfer of an acetyl group to the lysine residues in proteins, this process is mediated by acetyltransferases that are divided into several families. Similarly, deacetylation is brought about by several different classes of protein deacetylases. The roles of lysine acetylation in the regulation of gene expression through the reversible modification of core histone tails or transcription factors were well studied. Lysine acetylation has been found to play important roles in various other cellular processes since 1996 in some independent studies. However, until the year 2009, high-throughput mass spectrometry makes it possible to study acetylation in proteomics levels. Lysine acetylation could be found in almost everywhere. Scientists found that lysine acetylation preferentially targets proteins involved in diverse cellular processes, such as chromatin remodeling, cell cycle, nuclear transport, and cellular metabolism. In this review, we will focus on the roles of lysine acetylation on cellular metabolism, and illustrate that reversible acetylation of metabolic enzymes represents a metabolic regulatory mechanism conserved from bacteria to mammals.

Abstract:Ferroptosis is proposed to result from overwhelming iron-dependent oxidative injury, which is distinct from apoptosis, necrosis, and autophagy. This iron-dependent process is marked by increased levels of cytosolic and lipid reactive oxygen species (ROS) and abnormally small mitochondria with increased membrane density. Ferroptosis is similar to glutamate-induced excitotoxicity. Recently, many reports have revealed that ferroptosis is precisely regulated by some cellular signaling pathways, like apoptosis, including regulators of iron homeostasis, RAS pathway induction of oxidase gene expression, and cystine transport impacting glutathione synthesis. Ferroptosis contributes to the process of neurodegeneration and strategy to kill RAS-mutant cancer cells.

Abstract:The present study aimed to examine the role of visual magnocellular pathway in the recognition of Chinese character. Twenty-four university students took part in this study. We simultaneously manipulated the spatial frequency and temporal frequency of Chinese characters in order to dissociate two visual conditions, that is, the visual magnocellular (M) condition and visual control condition. And a global/local decision task was adopted here to get the comparison between global processing and local processing within each visual condition. The reaction time and error rate were recorded. Results showed that in the M condition, participants responded faster in global decision than in local decision, a global precedence effect appeared; while non-significant difference in the control condition. Similarly, higher error rate was found for local decision comparing with global decision only in the M condition. It suggested that the visual magnocellular system contributes to the global processing of Chinese character.

Abstract:ZNF403 and LCRG1 are two alternative splicing isoforms from human gene ZNF403. Previous study shows that LCRG1 displays tumor-suppressive properties in laryngeal carcinoma cell line Hep-2 cells. The aim of this study is to clarify the relationships between these two isoforms and further investigate the role of ZNF403 in tumor cells. Realtime PCR analysis was first applied to demonstrate the relative abundance of these two isoforms and showed that ZNF403 is the major transcription product. The function of ZNF403 in cell growth was next accessed by MTT assay and tumor growth in nude mice analysis, respectively. The results indicated that ZNF403 knockdown resulted in inhibition of cell growth in Hep-2 cell both in vitro and in vivo. Moreover, bioinformatics analysis, flow-cytometric analysis and PCR array analysis were performed to elucidate the mechanism under the role of ZNF403 in cell growth. Knockdown of ZNF403 significantly decreased the rate of DNA synthesis and mitosis. Additionally, a number of key cell-cycle regulating components such as MCM2, p21, ATM and MRE11A were identified to be mediated by ZNF403. Altogether, our findings suggest that ZNF403 is a novel cell cycle regulator, which may play an essential role in tumorigenesis.

Abstract:It has been shown that some miRNAs are related with tumor invasion and metastasis directly or indirectly. Our aim is to find a specific miRNA which plays an essential role in tumor metastasis. Although it has been shown that miR-132 was associated with blood vessel growth, neural development and differentiation, and inflammation, relationship between miR-132 and tumor metastasis was not studied in any research. In order to identify the effect of miR-132 on tumor metastasis, the migration ability in vitro was detected on breast cancer cell line MDA-MB-231 cells transducted with miR-132 (miR-132 group) and or mock miRNA (control group) by transwell assay. The results demonstrated significantly lower migration ratio in miR-132 case compared to that in control case, indicating inhibition effects on cancer migration of miR-132. To clarify the inhibition mechanism by which miR-132 inhibits cancer metastasis, target genes of miR-132 were screened and identified. They are CHIP (STUB1), G3BP1 and G3BP2. The expression levels of these 3 genes in MCF7 cells (metastasis cell line) and MDA-MB-231 cells with or without transduction of miR-132 or mock miRNA were detected by PCR and Real-time PCR. Two key genes, G3BP1/G3BP2, were founded to be involved in the regulation of miR-132 to tumor metastasis, demonstrating that miR-132 could silence G3BP1/G3BP2, which resulted in the suppression of tumor metastasis. Our research suggests that miR-132 may be an important potential target used for inhibition of cancer metastasis and clinical therapy of cancer, and shed light on the suppression mechanisms of miR-132.

Abstract:Based on our previous solexa sequencing data, combining with bioinformatics analysis of microRNA expression changes in porcine adipose tissue from different growth phases in a model of obesity, we found the expression level of miR-191 was significantly different in developing swine adipose tissue. In this research, we successfully overexpressed miR-191's transcripts by recombinant adenovirus in primary cultured porcine preadipocytes, and then investigated the impact on differentiation of pig preadipocyte by Real-time quantitative PCR, Western blot. The results showed that miR-191's expression level gradually increased during differentiation. The miR-191 transcripts increased dramatically when miR-191 overexpressed compared to the control group, which caused the decrease of C/EBPβ, PPARγ and aP2's mRNA level and the sequentially repression of preadipocytes differentiation. Meanwhile, Western blotting results indicated that the expression of C/EBPβ protein in primary cultured porcine preadipocytes that overexpressed miR-191 was 55% lower than that in control cells after 48 h post-transfection. Importantly, we predicted that C/EBPβ was miR-191's target gene through bioinformatics software TargetScan and MicroInspector. This is conformed by dual luciferase reporter vector system assay which showed that miR-191 can target C/EBPβ 3′ untranslated region (3′UTR) directly and then decrease its expression. In conclusion, this study indicates that miR-191 can attenuate pig preadipocytes defferetiation possibly by repressing the gene expression of C/EBPβ which is one of the early marker gene of adipocytes differentiation.

Abstract:Selective binding of transcription factors (TFs) to cis-regulatory elements plays an important role in cell-type specific gene expression in mammalian cells. This process is potentially guided by epigenetic states of the chromatin. Recent studies provide large amounts of genome-wide ChIP-seq data for both TF binding and histone modification loci, enabling large-scale analysis of spatial and regulatory interplay between TFs and epigenetic marks. In this paper, the authors report an integrative analysis of multiple public ChIP-seq and RNA-seq data sets, concerning 85 TFs, 9 histone modifications and 5 cell lines, to investigate the genome-wide localization correlations between transcription factor binding sites (TFBSs), histone modification patterns and transcription in human. This study reveals that genome-wide co-localization with histone modifications follow the same pattern for different TFs, and active histone marks typically adjoin TFBSs at a distance around 500 bp. TF occupancy at conserved sequences is found positively correlated with levels and bimodal pattern of active histone marks, and the bimodal and co-localized patterns track with higher gene expression. The correlation among histone modification patterns, TF occupancy and gene transcription suggests the existence of a possible regulatory mechanism that cells may implement to regulate transcription.

Abstract:The nematode Caenorhabditis elegans has been widely used as a perfect model organism to study the relationship between genes and behavior. The pharyngeal microcircuit of the worm controls a complex feeding behavior. In order to study the molecular basis of this feeding behavior, it is necessary to identify subtle differences in feeding activity of the worm. However, most of the phenotype analyzing of feeding behavior is accomplished by human eyes. And it is a tough and poor efficiency job to analyze the fast pumping muscle of the worm. To help improving this problem, an automated system has been developed based on computer vision for the high-throughput analysis of the feeding behavior by virtue of a simple webcam. Our system enables the consistent and subtle analysis of C. elegans pumping recordings and the accuracy of pumping detection is up to 98%. Under this high accuracy, the time cost of the behavior analysis is cut down by 67% versus human manipulation.