DEYA2在肺腺癌中表达升高(英文)

Objective:Lung cancer has emerged as a leading cause of cancer death in the world.Eyes Absent (EYA) is an important and conserved transcriptional regulator of development.The aim of the present study was to identify the expression of Drosophila Eyes Absent Homologue 2 (EYA2) in non-small cell lung cancer (NSCLC) and to investigate their correlation with clinical parameters.Methods:Fresh,paired lung samples (n=59) of NSCLC were obtained by surgical resection at the Department of Thoracic Surgery of the People's Liberation Army General Hospital.Expression of EYA2 were examined by Western blot and immunohistochemical analysis in specimens of NSCLC and paired normal lung tissue.Clinical data,patho-logic result and Ki67 expression were collected and subsequent correlation with EYA2 expression was analyzed.Results:EYA2 expression was found located in cytoplasm and nucleus,but mostly in cytoplasm.The expression of EYA2 increased in NSCLC by Western blot and immunohistochemistry,which was correlated with histology type,but not correlated with gender,age,pTNM stage,histological differentiation and lymph node metastasis.Compared with normal lung tissue,the expres-sion of EYA2 significantly was up-regulated in lung adenocarcinoma,while no significant difference in lung squamous cell carcinoma.Expression of EYA2 was uncorrelated with expression of Ki67 in NSCLC.Conclusion:Expression of EYA2 was augmented in lung adenocarcinoma.EYA2 is likely participating in tumorigenesis and development of lung adenocarcinoma as transcriptional activator.

HUNK inhibits cargo uptake and lysosomal traffic in the caveolar pathway via the AGAP3/ARF6

Endocytosis is a crucial cellular process that takes up cargos by enclosing them in membrane-bound vesicles,and transports cargos to different parts of the cell,such as the lysosomes[1].Endocytosis is classified into several mechanistically and morphologically pathways,including clathrin-mediated endocytosis(CME)and caveolae-mediated endocytosis(CavME)[1,2].

Interaction of Hsp40 with influenza virus M2 protein: implications for PKR signaling pathway

Influenza virus contains three integral membrane proteins:haemagglutinin,neuraminidase,and matrix protein(M1 and M2).Among them,M2 protein functions as an ion channel,important for virus uncoating in endosomes of virus-infected cells and essential for virus replication.In an effort to explore potential new functions of M2 in the virus life cycle,we used yeast two-hybrid system to search for M2-associated cellular proteins.One of the positive clones was identified as human Hsp40/Hdj1,a DnaJ/Hsp40 family protein.Here,we report that both BM2(M2 of influenza B virus)and A/M2(M2 of influenza A virus)interacted with Hsp40 in vitro and in vivo.The region of M2-Hsp40 interaction has been mapped to the CTD1 domain of Hsp40.Hsp40 has been reported to be a regulator of PKR signaling pathway by interacting with p58^(IPK) that is a cellular inhibitor of PKR.PKR is a crucial component of the host defense response against virus infection.We therefore attempted to understand the relationship among M2,Hsp40 and p58^(IPK) by further experimentation.The results demonstrated that both A/M2 and BM2 are able to bind to p58^(IPK)in vitro and in vivo and enhance PKR autophosphorylation probably via forming a stable complex with Hsp40 and P58^(IPK),and consequently induce cell death.These results suggest that influenza virus M2 protein is involved in p58^(IPK)mediated PKR regulation during influenza virus infection,therefore affecting infected-cell life cycle and virus replication.

Metabolism and immunity in breast cancer

Breast cancer is one of the most common malignancies that seriously threaten women’s health.In the process of the malignant transformation of breast cancer,metabolic reprogramming and immune evasion represent the two main fascinating characteristics of cancer and facilitate cancer cell proliferation.Breast cancer cells generate energy through increased glucose metabolism.Lipid metabolism contributes to biological signal pathways and forms cell membranes except energy generation.Amino acids act as basic protein units and metabolic regulators in supporting cell growth.For tumor-associated immunity,poor immunogenicity and heightened immunosuppression cause breast cancer cells to evade the host’s immune system.For the past few years,the complex mechanisms of metabolic reprogramming and immune evasion are deeply investigated,and the genes involved in these processes are used as clinical therapeutic targets for breast cancer.Here,we review the recent findings related to abnormal metabolism and immune characteristics,regulatory mechanisms,their links,and relevant therapeutic strategies.

SARS-CoV-2 spike L452R mutation increases Omicron variant fusogenicity and infectivity as well as host glycolysis

Dear Editor,The SARS-CoV-2 Omicron variant has rapidly displaced the Delta variant and spread across the world.The Omicron variant harbors over 60 mutations,and 15 of the mutations are located in the receptor-binding domain(RBD).1 Compared with parental virus and previous variants,the Omicron variant is characterized by decreased hospitalization rates and less severe disease in patients.

The ubiquitin ligase E6AP facilitates HDAC6-mediated deacetylation and degradation of tumor suppressors

Dear Editor,Protein acetylation status can regulate protein stability via the ubiquitin-proteasome pathway,which plays a critical role in the regulation of various cellular functions and becomes a target for cancer therapy.1,2 Histone deacetylase 6(HDAC6)belongs to the class II of the histone deacetylase/acuc/apha family and regulates cancer cell proliferation,invasion,and metastasis.3 Combination of HDAC6 inhibitors(HDAC6i)with proteasome inhibitors(PI)shows synergistic anticancer activity.4 Although many studies reveal how acetyltransferases/deacetylases regulate protein acetylation and subsequent protein ubiquitination and degradation,whether an E3 ubiquitin ligase regulates protein acetylation remains largely unknown.In addition,the mechanisms undelying synergistic anticancer activity of HDAC6i and PI remain poorly understood.