Multiple myeloma (MM) is a haematological malignant disease with a clonal proliferation of plasma cells, and timely surveillance is helpful to improve the survival rate of patients with MM. However, there is a lack of simple and effective biomarkers for the diagnosis, prognosis, and residual disease evaluation of MM.In the detection cohort, we used the samples from six newly diagnosed MM patients and six control subjects. Plasma proteins were labelled with dimethyl reagents and enriched by lectin AANL6, then the deglycosylated peptides were identified by LC-MS/MS. Differentially expressed proteins were used for further exploration. In the validation cohort, we used 90 newly diagnosed patients with MM and 70 cases of unrelated diseases as controls. The diagnosis performance was analysed by ROC analysis using SPSS.In this study, we show, using lectin blots with AANL6, that glycosylation levels were higher in MM patients than in controls. After AANL6 enrichment, we detected 58 differentially expressed proteins using quantitative proteomics. We further validated one candidate Fibulin-1 (FBLN1). Using an Elisa assay, we showed that FBLN1 expression was increased in plasma of 90 cases of MM, and which was significantly correlated with DKK1 expression. ROC analysis showed that these two markers had a 95.7% specificity for determining the diagnosis of MM.These data suggest that the MM cases display increased glycosylation after AANL6 enrichment and that the combined expression of FBLN1 and DKK1 can be used as an effective diagnostic biomarker.
Abstract FOXM1 is a key transcriptional regulator involved in various biological processes in mammals, including carbohydrate and lipid metabolism, aging, immune regulation, development, and disease. Early studies have shown that FOXM1 acts as an oncogene by regulating cell proliferation, cell cycle, migration, metastasis, and apoptosis, as well as genes related to diagnosis, treatment, chemotherapy resistance, and prognosis. Researchers are increasingly focusing on FOXM1 functions in tumor microenvironment, epigenetics, and immune infiltration. However, researchers have not comprehensively described FOXM1's involvement in tumor microenvironment shaping, epigenetics, and immune cell infiltration. Here we review the role of FOXM1 in the formation and development of malignant tumors, and we will provide a comprehensive summary of the role of FOXM1 in transcriptional regulation, interacting proteins, tumor microenvironment, epigenetics, and immune infiltration, and suggest areas for further research.
Abstract Glycosylation is a ubiquitous posttranslational modification and plays an important role in many processes, such as protein stability, folding, processing, and trafficking. Among glycosylation types, O‐glycosylation is difficult to analyze due to the complex glycan composition, low abundance and lack of glycosidases to remove the O‐glycans. Many methods have been applied to analyze the O‐glycosylation of membrane glycoproteins and secreted glycoproteins since the synthesis of O‐glycosylation occurred in the Golgi apparatus. In recent years, some O‐glycosylation has been reported in the nucleus. In this work, we present a proximity labeling strategy based on TurboID by combining core 1 β1‐3 galactosyltransferase (C1GalT1), which has been reported in the nucleus, to characterize nucleocytoplasmic O‐glycosylation in living HeLa cells. The O‐glycosylated protein C1GalT1 was biotinylated by the proximity labeling method in living HeLa cells overexpressing C1GalT1 fused by TurboID and enriched by streptavidin‐coated beads. Following digestion with trypsin and mass spectrometry analysis, 68 high‐confidence and 298 putative O‐glycosylated sites were identified on 366 peptides mapped to 267 proteins. These results indicated that the proximity labeling method is a highly efficient technique to identify O‐glycosylation. Furthermore, the finding of abundant O‐glycosylation from nucleocytoplasmic proteins indicates a new pathway of O‐glycosylation synthesis in cells.
Multiple myeloma (MM) is a haematological malignant disease with a clonal proliferation of plasma cells, and timely surveillance is helpful to improve the survival rate of patients with MM. However, there is a lack of simple and effective biomarkers for the diagnosis, prognosis, and residual disease evaluation of MM. In the detection cohort, we used the samples from six newly diagnosed MM patients and six control subjects. Plasma proteins were labelled with dimethyl reagents and enriched by lectin AANL6, then the deglycosylated peptides were identified by LC-MS/MS. Differentially expressed proteins were used for further exploration. In the validation cohort, we used 90 newly diagnosed patients with MM and 70 cases of unrelated diseases as controls. The diagnosis performance was analysed by ROC analysis using SPSS. In this study, we show, using lectin blots with AANL6, that glycosylation levels were higher in MM patients than in controls. After AANL6 enrichment, we detected 58 differentially expressed proteins using quantitative proteomics. We further validated one candidate Fibulin-1 (FBLN1). Using an Elisa assay, we showed that FBLN1 expression was increased in plasma of 90 cases of MM, and which was significantly correlated with DKK1 expression. ROC analysis showed that these two markers had a 95.7% specificity for determining the diagnosis of MM. These data suggest that the MM cases display increased glycosylation after AANL6 enrichment and that the combined expression of FBLN1 and DKK1 can be used as an effective diagnostic biomarker.
ABSTRACT Mercury pollution is a kind of heavy metal pollution with great harm and strong toxicity which exists worldwide. Some microorganisms can convert highly toxic methylmercury into inorganic mercury compounds with significantly reduced toxicity. This is an effective means of methylmercury pollution remediation. As a safe microorganism with great potential in the remediation of heavy metal pollution, Rhodotorula mucilaginosa has not been studied in the remediation of methylmercury. Here, a R. mucilaginosa strain Rm4 with high methylmercury resistance was obtained by wild-strain screening. Its minimal inhibitory concentration and minimum lethal concentration reached 3 and 6 mg/L, respectively. At the same time, Rm4 can also degrade methylmercury. Unlike the traditional microbial methylmercury degradation pathways, R. mucilaginosa ’s genome does not encode the organomercury lyase gene MerB. However, transcriptomic analysis revealed that the glutathione reductase of R. mucilaginosa responds to the methylmercury degradation process. Structural domain analysis and molecular docking experiments suggest that the glutathione reductase of R. mucilaginosa has the potential to directly or indirectly participate in methylmercury degradation metabolism. Metabolic indicator tests of engineered strains overexpressing the glutathione reductase encoding gene also support this notion. IMPORTANCE The remediation of methylmercury pollution is crucial for environmental health. The ability of Rhodotorula mucilaginosa to resist and degrade methylmercury offers a new avenue for bioremediation efforts. Understanding the metabolic pathways involved, particularly the role of glutathione reductase, enhances our knowledge of how Rhodotorula mucilaginosa responds to methylmercury and opens up new possibilities for future research in bioremediation strategies.
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