Increased CSN5 expression enhances the sensitivity to lenalidomide in multiple myeloma cells.

Lenalidomide (LEN) is commonly used as an effective therapeutic agent for multiple myeloma (MM). However, in some patients, primary resistance to LEN is observed, the mechanisms of which remain poorly understood. In this study, we combined a LEN sensitivity assay with proteomics data from 15 MM cell lines to identify protein expression profiles associated with primary LEN resistance.

jPOST environment accelerates the reuse and reanalysis of public proteome mass spectrometry data.

jPOST (https://jpostdb.org/) comprises jPOSTrepo (https://repository.jpostdb.

Altered O-linked glycosylation in benign and malignant meningiomas.

Background: Changes in protein glycosylation have been reported in various diseases, including cancer; however, the consequences of altered glycosylation in meningiomas remains undefined. We established two benign meningioma cell lines-SUT-MG12 and SUT-MG14, WHO grade I-and demonstrated the glycan and glycosyltransferase profiles of the mucin-type O-linked glycosylation in the primary benign meningioma cells compared with two malignant meningioma cell lines-HKBMM and IOMM-Lee, WHO grade III. Changes in O-linked glycosylation profiles in malignant meningiomas were proposed.

Establishment and characterization of a novel cancer stem-like cell of cholangiocarcinoma.

Cholangiocarcinoma (CCA) is an aggressive malignant tumor of bile duct epithelia. Recent evidence suggests the impact of cancer stem cells (CSC) on the therapeutic resistance of CCA; however, the knowledge of CSC in CCA is limited due to the lack of a CSC model. In this study, we successfully established a stable sphere-forming CCA stem-like cell, KKU-055-CSC, from the original CCA cell line, KKU-055.

SIRT7 suppresses energy expenditure and thermogenesis by regulating brown adipose tissue functions in mice.

Brown adipose tissue plays a central role in the regulation of the energy balance by expending energy to produce heat. NAD-dependent deacylase sirtuins have widely been recognized as positive regulators of brown adipose tissue thermogenesis. However, here we reveal that SIRT7, one of seven mammalian sirtuins, suppresses energy expenditure and thermogenesis by regulating brown adipose tissue functions.

Emerging roles of GALNT5 on promoting EGFR activation in cholangiocarcinoma: a mechanistic insight.

Cholangiocarcinoma (CCA) is a lethal cancer in that the incidence is now increasing worldwide. N-acetylgalactosaminyltransferase 5 (GALNT5), an enzyme that initiates the first step of mucin type-O glycosylation, has been reported to promote aggressiveness of CCA cells via the epithelial to the mesenchymal transition (EMT) process, and Akt/Erk activation. In this study, the clinical and biological relevance of GALNT5 and the molecular mechanisms by which GALNT5 modulated EGFR in promoting CCA progression were examined.

AT-hook DNA-binding motif-containing protein one knockdown downregulates EWS-FLI1 transcriptional activity in Ewing's sarcoma cells.

Ewing's sarcoma is the second most common bone malignancy in children or young adults and is caused by an oncogenic transcription factor by a chromosomal translocation between the EWSR1 gene and the ETS transcription factor family. However, the transcriptional mechanism of EWS-ETS fusion proteins is still unclear. To identify the transcriptional complexes of EWS-ETS fusion transcription factors, we applied a proximal labeling system called BioID in Ewing's sarcoma cells.

Water Droplet-in-Oil Digestion Method for Single-Cell Proteomics.

Recent advances in single-cell proteomics highlight the promise of sensitive analyses in limited cell populations. However, technical challenges remain for sample recovery, throughput, and versatility. Here, we first report a water droplet-in-oil digestion (WinO) method based on carboxyl-coated beads and phase transfer surfactants for proteomic analysis using limited sample amounts.

Bioinformatic Prediction of Novel Signaling Pathways of Apoptosis-inducing Factor, Mitochondrion-associated 3 (AIFM3) and Their Roles in Metastasis of Cholangiocarcinoma Cells.

Background/aim: We previously demonstrated that a mitochondrial protein, apoptosis-inducing factor, mitochondrion-associated 3 (AIFM3) is over-expressed in cholangiocarcinoma (CCA) and its serum levels can be a prognostic biomarker for CCA. To elucidate the functional roles of AIFM3 in CCA progression, we aimed to determine the signaling pathways of AIFM3 in CCA.

Materials And Methods: AIFM3 gene in CCA cells was silenced and AIFM3-related proteins were identified using mass spectrometry and bioinformatics tools.

Targeting alpha2,3-sialylated glycan in glioma stem-like cells by Maackia amurensis lectin-II: A promising strategy for glioma treatment.

Glioma stem/initiating cells have been considered a major cause of tumor recurrence and therapeutic resistance. In this study, we have established a new glioma stem-like cell (GSC), named U373-GSC, from the U373 glioma cell line. The cells exhibited stemness properties, e.

EGFR-Targeted Pentacyclic Triterpene Analogues for Glioma Therapy.

Glioma, particularly its most malignant form, glioblastoma multiforme (GBM), is the most common and aggressive malignant central nervous system tumor. The drawbacks of the current chemotherapy for GBM have aroused curiosity in the search for targeted therapies. Aberrantly overexpressed epidermal growth factor receptor (EGFR) in GBM results in poor prognosis, low survival rates, poor responses to therapy and recurrence, and therefore EGFR-targeted therapy stands out as a promising approach for the treatment of gliomas.

Purification, Characterization, and Gene Expression of Rice Endo-β--Acetylglucosaminidase, Endo-Os.

In the endoplasmic reticulum-associated degradation system of plant and animal cells, high-mannose type free -glycans (HMT-FNGs) are produced from misfolded glycoproteins prior to proteasomal degradation, and two enzymes, cytosolic peptide:-glycanase (cPNGase) and endo-β-acetylglucosaminidase (endo-β-GlcNAc-ase), are involved in the deglycosylation. Although the physiological functions of these FNGs in plant growth and development remain to be elucidated, detailed characterization of cPNGase and endo-β-GlcNAc-ase is required. In our previous work, we described the purification, characterization, and subcellular distribution of some plant endo-β-GlcNAc-ases and preliminarily reported the gene information of rice endo-β-GlcNAc-ase (Endo-Os).

Multi-serum glycobiomarkers improves the diagnosis and prognostic prediction of cholangiocarcinoma.

Background: Aberrant glycosylation has been reported to play important roles in progression of cholangiocarcinoma (CCA) and hence the aberrant expressed glycans are beneficial markers for diagnosis and prognostic prediction of CCA.

Methods: Five CCA-associated glycobiomarkers-carbohydrate antigen 19-9 (CA19-9), carbohydrate antigen-S27 (CA-S27), CCA-associated carbohydrate antigen (CCA-CA), WFA-positive MUC1 (WFA-MUC1), and WFA-positive M2BP (WFA-M2BP), in the sera from CCA patients (N = 138) were determined in comparison with non-CCA control subjects (N = 246).

Results: Receiver operating characteristic analysis suggested the significance of each glycobiomarker in discriminating CCA from non-CCA with area under curve of 0.

The O-GalNAcylating enzyme GALNT5 mediates carcinogenesis and progression of cholangiocarcinoma via activation of AKT/ERK signaling.

Mucin type O-glycosylation is a posttranslational modification of membrane and secretory proteins. Transferring of N-acetylgalactosamine, the first sugar of O-glycosylation, is catalyzed by one of the 20 isoforms of polypeptide N-acetylgalactosaminyltransferases (GALNTs). In this study, Vicia villosa lectin (VVL), a lectin that recognizes O-GalNAcylated glycans, was used to detect VVL-binding glycans (VBGs) in cholangiocarcinoma (CCA).

Isocitrate dehydrogenase gene mutations and 2-hydroxyglutarate accumulation in esophageal squamous cell carcinoma.

Isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) are key metabolic enzymes that convert isocitrate to α-ketoglutarate. Somatic point mutations in IDH1/2 confer a gain-of-function in cancer cells, resulting in overproduction of an oncometabolite, 2-hydroxyglutarate (2HG). 2HG interferes with cellular metabolism and epigenetic regulation, contributing to oncogenesis.

Identification of a Specific Translational Machinery via TCTP-EF1A2 Interaction Regulating NF1-associated Tumor Growth by Affinity Purification and Data-independent Mass Spectrometry Acquisition (AP-DIA).

Neurofibromatosis type 1 (NF1) is an autosomal dominant disease that predisposes individuals to developing benign neurofibromas and malignant peripheral nerve sheath tumors (MPNST). The mechanism of NF1-tumorigenesis or the curatives have not been established. Using unique trascriptome and proteome integration method, iPEACH (1), we previously identified translationally controlled tumor protein (TCTP) as a novel biological target for NF1-associated tumors (2).

The jPOST environment: an integrated proteomics data repository and database.

Rapid progress is being made in mass spectrometry (MS)-based proteomics, yielding an increasing number of larger datasets with higher quality and higher throughput. To integrate proteomics datasets generated from various projects and institutions, we launched a project named jPOST (Japan ProteOme STandard Repository/Database, https://jpostdb.org/) in 2015.

Artesunate and chloroquine induce cytotoxic activity on cholangiocarcinoma cells via different cell death mechanisms.

Chemotherapy for cholangiocarcinoma (CCA) is not quite successful. In this study, we revisited the possibility of artesunate (ART) and chloroquine (CQ), the antimalarial drugs, as therapeutic agents against CCA. The possible mechanisms of these drugs to exert cytotoxicity on CCA cells were also explored.

SIRT7 has a critical role in bone formation by regulating lysine acylation of SP7/Osterix.

SP7/Osterix (OSX) is a master regulatory transcription factor that activates a variety of genes during differentiation of osteoblasts. However, the influence of post-translational modifications on the regulation of its transactivation activity is largely unknown. Here, we report that sirtuins, which are NAD(+)-dependent deacylases, regulate lysine deacylation-mediated transactivation of OSX.

RBMX is a component of the centromere noncoding RNP complex involved in cohesion regulation.

Satellite I RNA, a noncoding (nc)RNA transcribed from repetitive regions in human centromeres, binds to Aurora kinase B and forms a ncRNP complex required for chromosome segregation. To examine its function in this process, we purified satellite I ncRNP complex from nuclear extracts prepared from asynchronized or mitotic (M) phase-arrested HeLa cells and then carried out LC/MS to identify proteins bound to satellite I RNA. RBMX (RNA-binding motif protein, X-linked), which was isolated from M phase-arrested cells, was selected for further characterization.

Ribosome Incorporation into Somatic Cells Promotes Lineage Transdifferentiation towards Multipotency.

Recently, we reported that bacterial incorporation induces cellular transdifferentiation of human fibroblasts. However, the bacterium-intrinsic cellular- transdifferentiation factor remained unknown. Here, we found that cellular transdifferentiation is caused by ribosomes.

Clinical significance of GalNAcylated glycans in cholangiocarcinoma: Values for diagnosis and prognosis.

Cancer cells exhibited the aberrant cancer-associated glycans that are potential biomarkers for diagnosis and monitoring of the cancer. In this study, Sophora japonica agglutinin (SJA) was used to detect SJA-specific N-acetylgalactosamine-associated glycans (SNAG) in liver tissues and sera from cholangiocarcinoma (CCA) patients. Whether SNAG could be the diagnostic and prognostic markers for CCA was evaluated.

Activation of Vimentin Is Critical to Promote a Metastatic Potential of Cholangiocarcinoma Cells.

Cholangiocarcinoma (CCA) is a highly metastatic tumor, and the majority of patients with CCA have a short survival time because there are no available effective treatments. Hence, a better understanding regarding CCA metastasis may provide an opportunity to improve the strategies for treatment. A comparison study between the highly metastatic cells and their parental cells is an approach to uncover the molecular mechanisms underlying the metastatic process.