OBJECTIVES: To study the impact of SURF4 expression level on long-term prognosis of gastric cancer (GC) and biological behaviors of GC cells. METHODS: SURF4 expression level in GC and its association with long-term patient prognosis were analyzed using publicly available databases and in 155 GC patients with low and high SURF4 expressions detected immunohistochemically. The Cox proportional hazard model and Kaplan-Meier survival curves were used to analyze independent prognostic predictors of GC and the 5-year survival rate of the patients with different SURF4 expression levels. Informatics analyses were conducted to explore the correlation of SURF4 expression level with immune cell infiltration in GC, SURF4-related differential genes and their associated pathways. In cultured GC cell line HGC-27, the effects of SURF4 knockdown and overexpression on proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) were investigated. RESULTS: Analysis of GEPIA dataset and immunohistochemical results suggested significant SURF4 overexpression in GC (P<0.05), which was associated with shortened 5-year survival time of the patients (χ²=38.749, P<0.001). The prognosis of GC was closely related to tumor stage T3-4, N2-3, CEA≥5 μg/L and CA19-9≥37 kU/L (P<0.05). SURF4 expression level was negatively correlated with activated B cells, NK cells and CD8⁺ effector memory T cells (P<0.05) and positively correlated with CD4⁺ T cells (P<0.05). GO and KEGG enrichment analysis suggested that SUFR4 may participate in GC carcinogenesis by promoting EMT through the tight junction pathway. In HGC-27 cells, SURF4 overexpression significantly decreased E-cadherin expression, increased N-cadherin expression, inhibited ZO-1 and claudin-1 expressions, and promoted cell proliferation, migration and invasion. CONCLUSIONS SURF4 is highly expressed in GC, and its overexpression is associated with a shortened 5-year survival of the patients possibly by enhancing tumor cell proliferation, migration and invasion via inhibiting tight junction proteins and promoting EMT.
Humans ; Stomach Neoplasms/metabolism* ; Cell Proliferation ; Cell Movement ; Epithelial-Mesenchymal Transition ; Cell Line, Tumor ; Neoplasm Invasiveness ; Prognosis ; Tight Junction Proteins/metabolism* ; Membrane Proteins/metabolism* ; Female ; Male

OBJECTIVES: To investigate the impact of high expression of transmembrane and coiled helix structural domain 1 (TMCO1) on prognosis of gastric cancer and the possible mechanisms. METHODS: TMCO1 expression in gastric cancer and its effect on gastric cancer progression and prognosis were analyzed using publicly available databases and clinical data of patients undergoing radical surgery in our hospital, and its possible biological functions were explored using KEGG and GO analyses. In gastric cancer HGC-27 cells, the effects of lentivirus-mediated TMCO1 overexpression and TMCO1 silencing on cell apoptosis, proliferation, invasion and migration were examined. RESULTS: TMCO1 expression was significantly elevated in gastric cancer tissues (P<0.05), and its high expression was positively correlated with cancer progression (P<0.001) and a lowered postoperative 5-year survival rate of the patients (P<0.05). Bioinformatic analyses suggested that TMCO1 may affect gastric cancer cell apoptosis via Wnt signaling. In HGC-27 cells, TMCO1 overexpression significantly promoted tumor cell proliferation, inhibited cell apoptosis, and enhanced cell migration and invasion, whereas TMCO1 silencing produced the opposite effects. Western blotting showed that β-catenin levels were significantly upregulated in TMCO1-overexpressing cells and downregulated in cells with TMCO1 silencing. CONCLUSIONS TMCO1 is overexpressed in gastric cancer tissues, and its high expression promotes gastric cancer progression and affects long-term prognosis of the patients possibly by activating the Wnt/ β-catenin signaling pathway to inhibit apoptosis of gastric cancer cells.
Humans ; Stomach Neoplasms/metabolism* ; Apoptosis ; Prognosis ; Cell Line, Tumor ; Cell Proliferation ; Cell Movement ; Wnt Signaling Pathway ; beta Catenin/metabolism* ; Gene Expression Regulation, Neoplastic

Objective:To explore the effect of LILRB2 on the proliferation and apoptosis of colorectal cancer SW480 cells, and to further explore its mechanism.Methods:Colorectal cancer SW480 cells were cultured in vitro and divided into blank control group, negative control group and experimental group. The expression of LILRB2 was detected by flow cytometry. The expression of LILRB2 was detected by qPCR, and the empty vector plasmid and the LILRB2 plasmid were transfected into SW480 cells respectively; cell proliferation was detected by CCK-8 method; cell apoptosis was detected by flow cytometry. Western blot was used to detect changes in the expression of related proteins.Results:The expression level of LILRB2 in SW480 was 0.84 ± 0.09, twice higher than that in FHC cells (0.38 ± 0.05) , and the difference was statistically significant ( P<0.05) . After virus infection, the expression of LILRB2 (0.48 ± 0.07) in SW480 cells of the experimental group decreased significantly. CCK-8 experiment results showed that after 12 hours of treatment, the proliferation of SW480 cells in the LILRB2 low expression experimental group was inhibited, and the percentage of apoptosis in SW480 cells in the LILRB2 low expression experimental group increased to 49.3%±1.2%, which was statistically significant ( P<0.05) compared with the percentage of apoptosis in the blank control group and the negative control group (7.48%±0.85%, 7.35%±0.93%) . The ROS level of SW480 cells in the experimental group with low LILRB2 expression was significantly higher than that in the blank control group and negative control group ( P<0.05) . After adding ROS scavenger NAC, the apoptosis of LILRB2 in the experimental group increased. Conclusion:The low expression of LILRB2 inhibits the proliferation of SW480 cells and induces apoptosis, which may play a role by regulating the level of ROS, providing a theoretical basis for the study of LILRB2 in colorectal cancer.

Bacterial multi-drug resistance (MDR) is a global challenge in the fields of medicine and health, agriculture and fishery, ecology and environment. The cross-region spread of antibiotic resistance genes (ARGs) among different species is one of the main cause of bacterial MDR. However, there is no effective strategies for addressing the intensifying bacterial MDR. The CRISPR-Cas system, consisting of clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR associated proteins, can targetedly degrade exogenous nucleic acids, thus exhibiting high application potential in preventing and controlling bacterial MDR caused by ARGs. This review briefly introduced the working mechanism of CRISPR-Cas systems, followed by discussing recent advances in reducing ARGs by CRISPR-Cas systems delivered through mediators (e.g. plasmids, bacteriophages and nanoparticle). Moreover, the trends of this research field were envisioned, providing a new perspective on preventing and controlling MDR.
Anti-Bacterial Agents ; Bacteriophages/genetics* ; CRISPR-Cas Systems ; Drug Resistance, Bacterial/genetics* ; Plasmids/genetics*

OBJECTIVE: To investigate the expression of the cell division- associated gene NUF2 in breast cancer and its clinical significance. METHODS: The expression of NUF2 in breast cancer tissues was analyzed using Oncomine database. The relationship between the expression of NUF2 and the prognosis of breast cancer was analyzed using the Kaplan-Meier Plotter database. Gene set enrichment analysis (GSEA) and GEO database were used to investigate the effect of NUF2 on gene enrichment. The String database was utilized to analyze the proteins associated with NUF2. The TIMER database was analyzed to assess the correlations of NUF2 with BUB1, MAD2L1 and MYC. The expressions of NUF2 mRNA in 8 pairs of breast cancer tissues and adjacent tissues were verified by q-PCR. RESULTS: Compared with that in normal breast tissue, NUF2 was significantly overexpressed in breast cancer ( < 0.001). The overall survival time (HR = 1.52, = 0.015) and the recurrence-free survival time (HR = 1.85, = 3.2e-14) of the patients with high NUF2 expression were significantly shorter than those of patients with low NUF2 expression. In patients with high NUF2 expression, the enriched genes were involved mainly in cell cycle, P53, G2/M, DNA repair, MYC, and PI3K-AKT-MTOR signaling pathways, which were associated with tumor proliferation, invasion, metastasis and stemness. Combination of the results of String database, gene enrichment and TIMER database analyses suggested that NUF2 interacted directly with BUB1, MAD2L1, and MYC, which could promote the progression of breast cancer. The results of q-PCR showed that NUF2 expression was up-regulated in 6 cancer tissues and down-regulated in 2 cancer tissues. CONCLUSIONS NUF2 gene is overexpressed in breast cancer, and its expression level is important in predicting the prognosis of breast cancer.
Breast Neoplasms ; metabolism ; Cell Cycle Proteins ; metabolism ; Gene Expression Regulation, Neoplastic ; Humans ; Phosphatidylinositol 3-Kinases ; Prognosis

Objective To analyze the clinical characteristics and prognostic factors of elderly patients with cytogenetically normal acute myeloid leukemia (CN-AML). Methods A total of 104 initial CN-AML patients were enrolled in this retrospective study. The clinical characteristics were collected and analyzed retrospectively. Factors affecting complete remission (CR) were analyzed by using chi square test. Univariate and multivariate analyses of prognostic factors were performed by using Kaplan-Meier and Cox hazard regression model respectively. Results After the first chemotherapy, 72 of 104 patients were able to be evaluated the efficacy, the CR rate was 38.9%(28/72) and total response rate was 55.6%(40/72). The white cell count<100 × 109/L and NPM1 mutation were related to a higher CR rate [59.4%(38/64) vs. 12.5%(1/8), 83.3%(10/12) vs. 36.4%(8/22), P<0.05]. Among 104 patients, the median overall survival (OS) was 6.9 months. Univariate analysis results demonstrated that age≥70 years, secondary AML, white cell count≥100×109/L, FLT3-ITD mutation, CD7 expression, achieving CR beyond 2 cycles of induction therapy and CCI score≥2 were influence factors on OS. In multivariable analysis, FLT3-ITD mutation (HR=7.61, 95%CI 1.80-32.11, P= 0.006) and achieving CR beyond 2 cycles of induction therapy (HR= 10.11, 95 % CI 2.38-43.03, P=0.002) were independent prognostic factors for OS in elderly patients with CN-AML. Conclusion The prognosis of elderly patients with CN-AML is the result of the combined effect of many factors, FLT3-ITD mutation and achieving CR beyond 2 cycles of induction therapy are independent prognostic factors in elderly patients with CN-AML.

Protein phosphatase 2A (PP2A) accounts for the majority of total Ser/Thr phosphatase activities in most cell types and regulates many biological processes. PP2A holoenzymes contain a scaffold A subunit, a catalytic C subunit, and one of the regulatory/targeting B subunits. How the B subunit controls PP2A localization and substrate specificity, which is a crucial aspect of PP2A regulation, remains poorly understood. The kinetochore is a critical site for PP2A functioning, where PP2A orchestrates chromosome segregation through its interactions with BubR1. The PP2A-BubR1 interaction plays important roles in both spindle checkpoint silencing and stable microtubule-kinetochore attachment. Here we present the crystal structure of a PP2A B56-BubR1 complex, which demonstrates that a conserved BubR1 LxxIxE motif binds to the concave side of the B56 pseudo-HEAT repeats. The BubR1 motif binds to a groove formed between B56 HEAT repeats 3 and 4, which is quite distant from the B56 binding surface for PP2A catalytic C subunit and thus is unlikely to affect PP2A activity. In addition, the BubR1 binding site on B56 is far from the B56 binding site of shugoshin, another kinetochore PP2A-binding protein, and thus BubR1 and shugoshin can potentially interact with PP2A-B56 simultaneously. Our structural and biochemical analysis indicates that other proteins with the LxxIxE motif may also bind to the same PP2A B56 surface. Thus, our structure of the PP2A B56-BubR1 complex provides important insights into how the B56 subunit directs the recruitment of PP2A to specific targets.
Amino Acid Motifs ; Binding Sites ; Cell Cycle Proteins ; chemistry ; Crystallography, X-Ray ; Humans ; Multienzyme Complexes ; chemistry ; Protein Phosphatase 2 ; chemistry ; Protein Structure, Quaternary ; Protein-Serine-Threonine Kinases ; chemistry

SOX17,a member of the SOX family of transcription factors,is conserved in many species and plays an important role in the formation of embryo endoderm.A number of studies have found that SOX17 gene expression is silenced or decreased might be due to promoter bypermethylation,which plays a vital role in tumorigenesis and tumor progression,and may contribute to aberrant activation of canonical Wnt signaling pathway in several human malignant tumors.