SPOP regulates the expression profiles and alternative splicing events in human hepatocytes.

Speckle type BTB/POZ protein (SPOP) may have cancer promoting or inhibiting effects. At present, the role of SPOP in hepatocellular carcinoma (HCC) has rarely been studied. In this study, to investigate the effects of SPOP in HCC and elucidate the underlying molecular mechanisms of its relationship with genes, differentially expressed genes (DEGs) were classified through RNA sequencing. The gene ontology analysis and Kyoto Encyclopedia of Genes and Genomes functional pathway analysis were used to further predict the function of DEGs after the overexpression of SPOP. The biological function of SPOP-regulated alternative splicing events in cells is comprehensively assessed. The Cancer Genome Atlas database and Gene Expression Omnibus dataset were performed to evaluate the correlation between SPOP and HCC progression. Due to SPOP overexpression, 56 DEGs in the HCC related pathway were further identified. The results showed that SPOP overexpression facilitated the cell proliferation and changed the gene expression profiles of human normal hepatocytes. SPOP-regulated alternative splicing events were involved in pathways associated with cellular processes, metabolism, environmental information procession, organismal systems, and so on. In conclusion, SPOP may potentially exhibit tumor-promoting effects, necessitating further investigations to unveil its molecular mechanisms comprehensively.

A novel disulfidptosis-related immune checkpoint genes signature: forecasting the prognosis of hepatocellular carcinoma.

BACKGROUND: HCC is an extremely malignant tumor with a very poor prognosis. In 2023, a brand-new kind of cell death known as disulfidptosis was identified. Although, the prognosis as well as expression of immune checkpoints that are closely connected with it in HCC remain unknown. METHODS: In this work, we identified 49 genes with abnormal expression in liver cancer and normal liver tissue, with 23 of them being differentially expressed genes. To create a signature, we classified all HCC cases into three subtypes and used the TCGA database to evaluate each relevant gene's prognostic value for survival. RESULTS: Five gene signatures were identified using the LASSO Cox regression approach, while those diagnosed with HCC were split into either low- or high-risk groups. Patients having low-risk HCC showed a much greater likelihood of surviving than those with high risk (p < 0.05). Through immune cell infiltration analysis, it was found that immune-related genes were abundant in high-risk groups and had reduced immune status. CONCLUSION: In conclusion, immune checkpoint genes highly associated with disulfidptosis contribute to tumor immunity and can be used to evaluate HCC prognosis. When it comes to predicting overall survival (OS) time in HCC, risk score has been set to be a separate predictor. Through immune cell infiltration analysis, it was found that immune-related genes were abundant in high-risk groups and had reduced immune status. It is possible to measure the prognosis of HCC based on immune checkpoints genes strongly linked to disulfidptosis.

MICALL2 as a substrate of ubiquitinase TRIM21 regulates tumorigenesis of colorectal cancer.

BACKGROUND: Molecule interacting with CasL-like protein 2 (MICALL2) is believed to regulate cytoskeleton dynamics, tight junction formation, and neurite outgrowth. However, its biological role and the underlying mechanism in colorectal cancer (CRC) remain largely elusive. METHODS: qRT-PCR, Western blotting and immunohistochemistry assays were used to detect the expression levels of different genes. Next, mass spectrometry, co-immunoprecipitation and immunofluorescence staining were used to detect the interactions of proteins. Furthermore, MTT assay, colony formation assay, wound-healing assays and xenograft tumor models were performed to demonstrate the functions of MICALL2 in CRC. In addition, transcriptome sequencing and Western blotting were conducted to verify the mechanism of MICALL2 in CRC. RESULTS: We found that both mRNA and protein levels of MICALL2 are up-regulated in colorectal cancer tissues compared with non-tumor tissues and that its overexpression is closely correlated with poor prognosis. Ubiquitin E3 ligase Tripartite motif-containing protein 21 (TRIM21) mediated MICALL2 ubiquitination and proteasome-dependent degradation, negatively correlated with MICALL2 levels, and reversely regulated the tumorigenic activity of MICALL2 in CRC. Functional studies confirmed that MICALL2 promoted colorectal cancer cell growth and migration via the Wnt/ß-catenin signaling pathway. CONCLUSIONS: As a substrate of ubiquitinase TRIM21, MICALL2 enhances the growth and migration of colorectal cancer cells and activates the Wnt/ß-catenin signaling pathway. Video abstract.

Iterative Synthesis of 2-Deoxyoligosaccharides Enabled by Stereoselective Visible-Light-Promoted Glycosylation.

The photoinitiated intramolecular hydroetherification of alkenols has been used to form C-O bonds, but the intermolecular hydroetherification of alkenes with alcohols remains an unsolved challenge. We herein report the visible-light-promoted 2-deoxyglycosylation of alcohols with glycals. The glycosylation reaction was completed within 2 min in a high quantum yield (ϕ=28.6). This method was suitable for a wide array of substrates and displayed good reaction yields and excellent stereoselectivity. The value of this protocol was further demonstrated by the iterative synthesis of 2-deoxyglycans with α-2-deoxyglycosidic linkages up to a 20-mer in length and digoxin with ß-2-deoxyglycosidic linkages. Mechanistic studies indicated that this reaction involved a glycosyl radical cation intermediate and a photoinitiated chain process.

Research progress on the relationship between TM6SF2 rs58542926 polymorphism and non-alcoholic fatty liver disease.

INTRODUCTION: nonalcoholic fatty liver disease is a common liver disease with a global average prevalence of about 25%. In addition to the incidence of NAFLD being related to obesity, diabetes, hyperlipidemia, etc., genetic factors also have an important impact on the incidence of NAFLD. AREAS COVERED: Current experimental results and clinical studies show that the transmembrane 6 superfamily member 2 (TM6SF2) gene plays an important role in the pathogenesis of NAFLD. The research on genetic polymorphism of TM6SF2 gene mainly focuses on rs58542926 locus (rs58542926 c.449 C > T, p. Glu167Lys, E167K). The Mutations of this site might increase the risk of NAFLD in carriers. EXPERT OPINION: The mutation of this site causes the disorder of triglyceride metabolism in the liver, which leads to the deposition of a large amount of lipids in the liver, and further induces the incidence of NAFLD. With the study of the mechanism of TM6SF2 gene polymorphism in the pathogenesis of NAFLD, it is helpful to understand the molecular mechanism of the pathogenesis of NAFLD, which has a great value for the treatment of NAFLD.

A visualized ratiometric fluorescence sensing system for copper ions based on gold nanoclusters/perovskite quantum dot@SiO2 nanocomposites.

Excessive copper ions (Cu2+) cause serious environmental pollution and even endanger the health of organisms. Fluorescence chemosensing materials are widely used in the detection of metal ions due to their simple operation and high sensitivity. In this study, SiO2-encapsulated single perovskite quantum dot (PQD@SiO2) core-shell nanostructures which show strong, stable, and green fluorescence are synthesized and composited with gold nanoclusters (AuNCs) which show Cu2+-sensitive and red light-emitting fluorescence to obtain a visualized ratiometric fluorescence sensor (AuNCs/PQD@SiO2) for the detection of Cu2+. In the visualized detection of Cu2+, the green fluorescence emitted from the ion-insensitive PQD@SiO2 component is used as a reference signal and the red fluorescence emitted by ion-sensitive AuNC component is adopted as a sensing signal. In the presence of Cu2+, the red fluorescence is quenched whereas the green fluorescence remains stable, which results in a visualized fluorescence color change from orange-red to yellow and finally to green with increasing Cu2+ concentration. The significant change in the fluorescence color of AuNCs/PQD@SiO2 in response to Cu2+ enables a rapid, sensitive, and visualized detection of Cu2+. Further accurate and sensitive ratiometric fluorescence analysis of Cu2+ can be accomplished by measuring the ratio of fluorescence intensities at 643 and 520 nm (I643/I520) at a certain Cu2+ level. The developed AuNCs/PQD@SiO2-based sensor has been validated by its satisfactory application in the detection of Cu2+ in human serum and environmental water samples.

Novel carbohydrate-triazole derivatives as potential α-glucosidase inhibitors.

A series of novel pyrano[2, 3-d]trizaole compounds were synthesized and their α-glucosidase inhibitory activities were evaluated by in vitro enzyme assay. The experimental data demonstrated that compound 10f showed up to 10-fold higher inhibition (IC5074.0 ± 1.3 µmol·L-1) than acarbose. The molecular docking revealed that compound 10f could bind to α-glucosidase via the hydrophobic, π-π stacking, and hydrogen bonding interactions. The results may benefit further structural modifications to find new and potent α-glucosidase inhibitors.