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Background The Augmin Like Complex Subunit 5 (HAUS5) is involved in microtubule generation and centrosome assembly. Loss of HAUS5 function leads to loss of centrosome integrity, ultimately promoting tumor formation by causing functional defects and chromosome dislocation in the bipolar spindle. However, the role of HAUS5 in the development and progression of hepatocellular carcinoma (HCC) remains unclear. Methods and results This research dealt with investigating the role of HAUS5 in HCC and reported that HAUS5 is over-expressed in HCC tissues and cells. It was also found that its high expression levels were a crucial risk factor that affected HCC patients’ survival status. Correlation analysis depicted that HAUS5 expression was linked to immune infiltration in HCC. A nomogram model with good predictive capability with an area under the curve (AUC) value of 0.969 was constructed by integrating the clinical features of HCC and HAUS5 expression levels. HAUS5 knockdown remarkably attenuated the migration abilities and invasiveness of HCC cells. Conclusion HAUS5 is over-expressed in HCC tissues and could be used as a novel prognostic biomarker for patients with HCC.

Objective To investigate the expression of IFITM2 in colorectal cancer(CRC) and explore the effect of IFITM2 on proliferation, migration and invasion ability. Methods TCGA database was used to analysis the expression of IFITM2 in colorectal cancer, Western blot was chosen to detect the protein level of IFITM2 in colorectal cancer specimens and cell lines. Univariate and multivariate cox regression were used to analyze the association between IFITM2 and clinicopathological features. Kaplan-Meier Plotter tool was selected to evaluate the prognostic significance of IFITM2 gene expression in the TCGA database. A network comprising 50 most similar genes and IFITM2 was constructed with the STRING database. Gene set enrichment analysis (GSEA) was performed using LinkedOmics database. Transient transfection of IFITM2 siRNA and negative control was selected to construct SW480, HCT116 IFITM2 silence cells and control cells. CCK-8 and colony formation assays were selected to observe the effect of IFITM2 on CRC proliferation ability, transwell assays and wound healing assays were used to detect the effect of IFITM2 on CRC cell migration and invasion ability. Gene Set Enrichment Analysis (GSEA) was used to analyze IFITM2-associated pathways and Western blot was used for further verification. Results IFITM2 was over-expressed in CRC tissues and cells, High IFITM2 expression in CRC was obviously related to N stage, M stage and Pathologic stage. IFITM2 was a significant risk factor influencing the survival of CRC patients. The proliferation ability of SW480 and HCT116 cells was suppressed when IFITM2 was silenced, transwell assays showed IFITM2 silence weaken the migration and invasion ability of CRC cells. GSEA analysis showed IFITM2 was positively related with PI3K/AKT pathway, Western blot results confirmed that IFITM2 could activate PI3K/AKT pathway. Conclusion IFITM2 was over-expressed in colorectal cancer and modulated PI3K/AKT pathway to promote CRC cells proliferation and metastasis.

Introduction IFITM2 (interferon-induced transmembrane protein 2) is involved in the repression of viral infection. Recently, IFITM2 was found to be highly expressed in multiple cancers. However, the possible roles of IFITM2 in gastric cancer (GC) remain unclarified. In this research, we determined the expression of IFITM2 and its relationship with clinical outcome in GC.Methods The original data retrieved from bioinformatics databases were integrated by R package v3.6.2. The expression of IFITM2 in GC was explored by online databases of UALCAN. Immunohistochemistry staining and molecular analysis were conducted to validate IFITM2 expression in human GC cells and clinical specimens. The association between IFITM2 and clinicopathological features were analyzed by univariate/multivariate Cox regression. The prognostic significance of IFITM2 gene expression in the TCGA-STAD and GEO database were evaluated by TIMER and Kaplan-Meier Plotter tool. The relationships between IFITM2 and immune tumor characteristics were analyzed with TIMER 2.0. The biological function of IFITM2 were analyzed by GSEA. IFITM2-specific siRNA was employed to confirm the roles of IFITM2 in cell migration and wound healing.Results IFITM2 was over-expressed in GC and contributed to poor prognosis. High IFITM2 expression in GC was obviously related to T stage, distant metastasis, higher histologic grade. IFITM2 was a significant risk factor influencing the survival of GC patients. High IFITM2 expression was positively associated related to immune-infiltrating cells. The Cytokine-Cytokine-Receptor-Interaction pathway was remarkably enriched by IFITM2 upregulation. IFITM2 knockdown was found to significantly reduce the ability of cell migration and scratch repair.Conclusion IFITM2 is over-expressed in GC and affects the prognosis of GC patients. IFITM2 may act as a novel prognostic biomarker for GC patients.

The aim is to report the preliminary outcomes of percutaneous endovenous intervention (PEVI) for acute proximal deep vein thrombosis (DVT) secondary to iliac vein compression syndrome (IVCS) without inferior vena cava filter (IVCF) placement. Acute DVT patients who underwent PEVI without IVCF were analyzed retrospectively. PEVI consisted of catheter-directed thrombolysis, manual aspiration thrombectomy, balloon angioplasty and stenting. CT was used to evaluate the left common iliac vein (LCIV). Sixty-two consecutive patients (17 men and 45 women, mean age, 59.4 ± 15.2 years) were enrolled. The compression percentage of the LCIV ranged from 51.7% to 95.2% (median 83.2%). Iliac DVT was present in 7 patients; iliofemoral, in 30 patients; and iliofemoropopliteal, in 25 patients. Complete technical success and clinical improvement were obtained in all subjects without the occurrence of symptomatic pulmonary embolism (PE). Five patients experienced recurrent thrombosis. The primary patency rates at 12 and 24 months were 93.8% and 91.4%, respectively, which remained stable at 36, 48 and 60 months. The secondary patency rates at 12 and 24 months were 95.7% and 93.3%, respectively, and there was no change at 60 months. Although limited, our preliminary results suggested that PEVI without IVCF placement seemed to be safe and effective for acute proximal DVT secondary to IVCS without inferior vena cava thrombosis or symptomatic PE.

The role of specific cleavage of transcription repressor proteins by proteases and how this may be related to the emerging theme of dinucleotides as cellular signaling molecules is poorly characterized. The transcription repressor NmrA of Aspergillus nidulans discriminates between oxidized and reduced dinucleotides, however, dinucleotide binding has no effect on its interaction with the zinc finger in the transcription activator AreA. Protease activity in A. nidulans was assayed using NmrA as the substrate, and was absent in mycelium grown under nitrogen sufficient conditions but abundant in mycelium starved of nitrogen. One of the proteases was purified and identified as the protein Q5BAR4 encoded by the gene AN2366.2. Fluorescence confocal microscopy showed that the nuclear levels of NmrA were reduced approximately 38% when mycelium was grown on nitrate compared to ammonium and absent when starved of nitrogen. Proteolysis of NmrA occurred in an ordered manner by preferential digestion within a C-terminal surface exposed loop and subsequent digestion at other sites. NmrA digested at the C-terminal site was unable to bind to the AreA zinc finger. These data reveal a potential new layer of control of nitrogen metabolite repression by the ordered proteolytic cleavage of NmrA. NmrA digested at the C-terminal site retained the ability to bind NAD(+) and showed a resistance to further digestion that was enhanced by the presence of NAD(+). This is the first time that an effect of dinucleotide binding to NmrA has been demonstrated.

The role of specific cleavage of transcription repressor proteins by proteases and how this may be related to the emerging theme of dinucleotides as cellular signaling molecules is poorly characterized. The transcription repressor NmrA of Aspergillus nidulans discriminates between oxidized and reduced dinucleotides, however, dinucleotide binding has no effect on its interaction with the zinc finger in the transcription activator AreA. Protease activity in A. nidulans was assayed using NmrA as the substrate, and was absent in mycelium grown under nitrogen sufficient conditions but abundant in mycelium starved of nitrogen. One of the proteases was purified and identified as the protein Q5BAR4 encoded by the gene AN2366.2. Fluorescence confocal microscopy showed that the nuclear levels of NmrA were reduced approximately 38% when mycelium was grown on nitrate compared to ammonium and absent when starved of nitrogen. Proteolysis of NmrA occurred in an ordered manner by preferential digestion within a C-terminal surface exposed loop and subsequent digestion at other sites. NmrA digested at the C-terminal site was unable to bind to the AreA zinc finger. These data reveal a potential new layer of control of nitrogen metabolite repression by the ordered proteolytic cleavage of NmrA. NmrA digested at the C-terminal site retained the ability to bind NAD(+) and showed a resistance to further digestion that was enhanced by the presence of NAD(+). This is the first time that an effect of dinucleotide binding to NmrA has been demonstrated.