Characterization and identification of the integrin family in silkworm, Bombyx mori

YesAs an important economic insect, Bombyx mori is also a useful model organism for lepidopteran insect. Integrins are evolutionarily conserved fromsponges to humans, and play vital roles inmany physiological and pathological processes. To explore their diverse functions of integrins in insect, eleven integrins including sixα and five β subunitswere cloned and characterized fromsilkworm. Our results showed that integrins fromsilkwormown more family members compared to other invertebrates. Among those α subunits, integrins α1, α2, and the other four subunits belong to PS1, PS2, and PS3 groups, respectively. The β subunits mainly gather in the insect βν group except the β1 subunit which belongs to the insect β group. Expression profiles demonstrated that the integrins exhibited distinct patterns, but were mainly expressed in hemocytes. α1 and β2 subunits are the predominant ones either in the embryogenesis or larva stages. Interestingly, integrins were significantly up-regulated after stimulated by 20-hydroxyecdysone (20-E) in vivo. These results indicate that integrins performdiverse functions in hemocytes of silkworm. Overall, our results provide a newinsight into the functional and evolutionary features of integrins.National Basic Research Programof China (No. 2012cb114603), the Research Fund for the Doctoral Program of Higher Education of China (20130182110003), the Natural Science Foundation of Chongqing (cstc2013jcyjys0007), and the Fundamental Research Funds for the Central Universities (SWU111014)

Identification of Early Diagnostic and Prognostic Biomarkers via WGCNA in Stomach Adenocarcinoma

Stomach adenocarcinoma (STAD) is a leading cause of cancer deaths, and the outcome of the patients remains dismal for the lack of effective biomarkers of early detection. Recent studies have elucidated the landscape of genomic alterations of gastric cancer and reveal some biomarkers of advanced-stage gastric cancer, however, information about early-stage biomarkers is limited. Here, we adopt Weighted Gene Co-expression Network Analysis (WGCNA) to screen potential biomarkers for early-stage STAD using RNA-Seq and clinical data from TCGA database. We find six gene clusters (or modules) are significantly correlated with the stage-I STADs. Among these, five hub genes, i.e., MS4A1, THBS2, VCAN, PDGFRB, and KCNA3 are identified and significantly de-regulated in the stage-I STADs compared with the normal stomach gland tissues, which suggests they can serve as potential early diagnostic biomarkers. Moreover, we show that high expression of VCAN and PDGFRB is associated with poor prognosis of STAD. VCAN encodes a large chondroitin sulfate proteoglycan that is the main component of the extracellular matrix, and PDGFRB encodes a cell surface tyrosine kinase receptor for members of the platelet-derived growth factor (PDGF) family. Consistently, Gene Ontology (GO) analysis of differentially expressed genes in the STADs indicates terms associated with extracellular matrix and receptor ligand activity are significantly enriched. Protein-protein network interaction analysis (PPI) and Gene Set Enrichment Analysis (GSEA) further support the core role of VCAN and PDGFRB in the tumorigenesis. Collectively, our study identifies the potential biomarkers for early detection and prognosis of STAD

CSN6: a promising target for cancer prevention and therapy

CSN6 has recently received increased attention as a multifunctional protein involved in protein stability. CSN6 plays an important role in controlling cellular proliferation, apoptosis and metastasis, modulating signal transduction, as well as regulating DNA damage and repair. Most studies have demonstrated that CSN6 is significantly upregulated in human malignant tumors such as cervical cancer, papillary thyroid cancer, colorectal cancer, breast cancer, lung adenocarcinoma, and glioblastoma, and its expression is usually correlated with poor prognosis. In this review, we summarize recent available findings regarding the oncogenic role of CSN6 in tumors, and provide a better understanding of CSN6 function at the molecular level and its potential therapeutic implications in combating human cancer

Sanggenon C inhibits cell proliferation and induces apoptosis by regulating the MIB1/DAPK1 axis in glioblastoma

Abstract Sanggenon C (SC), a herbal flavonoid extracted from Cortex Mori, has been mentioned to possess more than one treasured organic properties. However, the molecular mechanism of its anti‐tumor impact in glioblastoma (GBM) remains unclear. In this study, we reported that SC displayed a GBM‐suppressing impact in vitro and in vivo with no apparent organ toxicity. SC dramatically suppressed cell proliferation‐induced cell apoptosis in GBM cells. Mechanistically, we unveiled that SC modulated the protein expression of death associated protain kinase 1 (DAPK1) by controlling the ubiquitination and degradation of DAPK1. Quantitative proteomic and Western blot analyses showed that SC improved DAPK1 protein degradation via decreasing the expression of E3 ubiquitin ligase Mindbomb 1 (MIB1). More importantly, the effects of SC on cell proliferation and apoptosis of GBM cells have been in part reversed through DAPK1 downregulation or MIB1 overexpression, respectively. These results indicated that SC might suppress cell proliferation and induce cell apoptosis by decreasing MIB1‐mediated DAPK1 degradation. Furthermore, we found that SC acted synergistically with temozolomide (TMZ), an anti‐cancer drug used in GBM, resulting in elevated chemotherapeutic sensitivity of GBM to TMZ. Collectively, our data suggest that SC might be a promising anti‐cancer agent for GBM therapy

Influence of interstitial carbon content on the microstructure, mechanical and electrochemical corrosion properties of CoFeNiMn multi-principal component alloys

In this study, the effects of carbon content on the microstructural evolution as well as compression and electrochemical corrosion properties of CoFeNiMn multi-principal component alloys (MPCAs) were investigated. A series of (Co25Fe25Ni25Mn25)100−xCx (x = 4, 5, 6, 7, 8) alloys were prepared by vacuum arc melting. Increasing carbon content, the structure transits from a single face-centered-cubic (FCC) phase into a mixed structure containing FCC phase and M23C6 carbides. The yield strength and hardness of the (Co25Fe25Ni25Mn25)100−xCx alloys were enhanced by increasing carbon content, which in turn decreases the ductility. The alloys containing eutectic carbides had a good combination of high yield strength (880 MPa), high fracture strength (2773 MPa), and large fracture strain (47%). Electrochemical measurements indicated that carbon content evidently affects the corrosion resistance of (Co25Fe25Ni25Mn25)100−xCx alloys in 3.5 wt% NaCl solution. Their corrosion resistance initially increases and then decreases with increasing carbon content. The increase in M23C6 carbides can accelerate pitting corrosion and degenerate their corrosion resistance. These findings not only provide comprehensive understanding of the carbon-alloyed behavior in FCC-type MPCAs but also show their potential engineering application as high-performance structural materials

RQC helical hairpin in Bloom's syndrome helicase regulates DNA unwinding by dynamically intercepting nascent nucleotides.

The RecQ family of helicases are important for maintenance of genomic integrity. Although functions of constructive subdomains of this family of helicases have been extensively studied, the helical hairpin (HH) in the RecQ-C-terminal domain (RQC) has been underappreciated and remains poorly understood. Here by using single-molecule fluorescence resonance energy transfer, we found that HH in the human BLM transiently intercepts different numbers of nucleotides when it is unwinding a double-stranded DNA. Single-site mutations in HH that disrupt hydrogen bonds and/or salt bridges between DNA and HH change the DNA binding conformations and the unwinding features significantly. Our results, together with recent clinical tests that correlate single-site mutations in HH of human BLM with the phenotype of cancer-predisposing syndrome or Bloom's syndrome, implicate pivotal roles of HH in BLM's DNA unwinding activity. Similar mechanisms might also apply to other RecQ family helicases, calling for more attention to the RQC helical hairpin