ABSTRACT
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.
Subject(s)
Humans , Breast Neoplasms , Metabolism , Cell Cycle Proteins , Metabolism , Gene Expression Regulation, Neoplastic , Phosphatidylinositol 3-Kinases , PrognosisABSTRACT
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.
Subject(s)
Humans , Amino Acid Motifs , Binding Sites , Cell Cycle Proteins , Chemistry , Crystallography, X-Ray , Multienzyme Complexes , Chemistry , Protein Phosphatase 2 , Chemistry , Protein Structure, Quaternary , Protein Serine-Threonine Kinases , ChemistryABSTRACT
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.