Ubiquitin-conjugating enzyme E2 J2 (UBE2J2) is an ubiquitin proteasome component that responds to proteotoxic stress. We found that UBE2J2 was highly expressed in cellular protrusions of HCCLM3 metastatic hepatocellular carcinoma (HC) cells. Immunohistochemical analyses showed that UBE2J2 was expressed at higher levels in HC patient tissues than in corresponding non-tumor tissues. Because cellular protrusions are important for cell invasion, we hypothesized that UBE2J2 promotes HC cell invasion. We used chip-based surface plasmon resonance (SPR) to assess possible mechanisms of UBE2J2-regulated HCCLM3 cell invasion. We found that p-EGFR interacted with UBE2J2, and this finding was confirmed by co-immunoprecipitation analysis. UBE2J2 overexpression activated endothelial-mesenchymal transition in the non-invasive SMMC7721 HC cell line, and promoted invasion. UBE2J2 silencing reduced HCCLM3 cell invasion and endocytosis, and downregulated p-EGFR expression. p-EGFR inhibition by lapatinib reduced UBE2J2-promoted cell invasion, suggesting p-EGFR is important for UBE2J2-mediated HCCLM3 cell invasion. These findings demonstrate that endocytosis by HC cells is closely related to invasion, and may provide new anti-HC therapeutic targets. UBE2J2 may also be a novel biomarker for clinical HC diagnosis.
Background: The World Health Organization has declared coronavirus disease 2019 (COVID-19) a public health emergency of global concern. Updated analysis of cases might help identify the risk factors of illness severity.
Results: The median age was 63 years, and 44.9% were severe cases. Severe patients had higher APACHE II (8.5 vs. 4.0) and SOFA (2 vs. 1) scores on admission. Among all univariable parameters, lymphocytes, CRP, and LDH were significantly independent risk factors of COVID-19 severity. LDH was positively related both with APACHE II and SOFA scores, as well as P/F ratio and CT scores. LDH (AUC = 0.878) also had a maximum specificity (96.9%), with the cutoff value of 344.5. In addition, LDH was positively correlated with CRP, AST, BNP and cTnI, while negatively correlated with lymphocytes and its subsets.
Conclusions: This study showed that LDH could be identified as a powerful predictive factor for early recognition of lung injury and severe COVID-19 cases.
Methods: We extracted data regarding 107 patients with confirmed COVID-19 from Renmin Hospital of Wuhan University. The degree of severity of COVID-19 patients (severe vs. non-severe) was defined at the time of admission according to American Thoracic Society guidelines for community acquired pneumonia.
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