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@#The aim of this study was to detect the effect and mechanism of EZH1/2 inhibitor UNC1999 on hepatocellular carcinoma cell line SMMC- 7721.【Methods】Two groups including DMSO group（control group）and UNC1999 group were treated with different concentration of DMSO and UNC1999 for different time，respectively，then OD values were detected by using CCK- 8 kit to screen the appropriate action concentration and time of UNC1999. Cell proliferation rate was detected with EdU（5-ethynyl-2-deoxyuridine）Cell Proliferation Kit. The clone formation ability of cell was investigated by clone formation assay. Wound healing assay and transwell assay were used to detect the ability of migration and invasion. Annexin V-FITC/PI double staining assay was performed to detect cell apoptosis. Flow cytometry was used to detect cell cycle. RNA-seq was performed to detect the cell transcriptomics. qRT-PCR was conducted to investigate the related genes，including EZH1，EZH2 and NECTIN4. Western blot was conducted to detect the expression of EZH1 ，EZH2 and H3K27me3. 【Results】 Compared with the control group ，the UNC1999 group showed lower cell proliferation，inhibited ability of migration and invasion（P < 0.05）. In UNC1999 group，G0/1 block occurred in the cell cycle（P<0.05），while cell apoptosis had no significant change（P > 0.05）.【Conclusion】UNC1999 could inhibit HCC by suppressing the expression of EZH1 and EZH2 both in protein level，as well as their function of catalyzing histone methylation. EZH1 and EZH2 play important roles in HCC，which may be potential targets for HCC treatment. UNC1999 could significantly promote the expression of NECTIN4 isoform which has been reported to be associated with the response to anti-cancer drug ，suggesting that the combination of EZH1/2 inhibitor and anti-cancer drug may exert greater effect of inhibiting HCC. This can provide a new idea for clinical drug treatment of liver cancer.
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AIM:To investigate the effects of curcumin on the abilities of migration and invasion in the lung cancer PC-9 cells, and to observe the relationship between curcumin and nectin-4 expression.METHODS:The viability, migration and invasion of lung cancer PC-9 cells treated with curcumin or transfected with siNectin-4 were measured by MTT assay, wound healing test and Transwell assay , respectively.The protein levels of nectin-4, p-AKT and AKT in the PC-9 cells treated with curcumin or transfected with siNectin-4 were detected by Western blot .RESULTS:Curcumin in-hibited the viability of PC-9 cells.The wound healing rates and the numbers of the transmembrane cells in curcumin 10μmol/L and 20 μmol/L groups were decreased compared with control group without curcumin treatment .The expression level of nectin-4 was reduced after curcumin treatment for 24 h.The viability of the PC-9 cells was significantly inhibited after transfected with siNectin-4 for 48 h or 72 h (P<0.01), and the wound healing rates was decreased in siNectin-4 group compared with NC group (P<0.01).The numbers of the transmembrane cells in siNectin-4 group was significantly reduced (P<0.01).Curcumin and knockdown of nectin-4 suppressed the activation of AKT pathway in PC-9 cells.In si-Nectin-4+curcumin group , the cell viability reduced compared with curcumin group , and wound healing rates , cell inva-sive ability and AKT phosphorylation levels were decreased .CONCLUSION:Curcumin inhibits migration and invasion of the lung cancer PC-9 cells via down-regulation of nectin-4 expression and inhibition of AKT pathway .
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Objective:To investigate the role of CD46 and Nectin-4 on Measles virus (MV) infecting human pulmonary alveolar epithelial cells (HPAEpiC),and the interaction between CD46 and Nectin-4.Methods: Measles virus was divided into pre-infection group and 2 h-infection group,HPAEpiCs treatment with anti-CD46 antibody and/or anti-Nectin-4 antibody as experimental groups,and untreated HPAEpiCs as a control.The variation of viral replication level was detected.A Co-immunoprecipitation assay (Co-IP) was used to explore whether CD46 and Nectin-4 had interactive relationship in MV infection.Results: Compared with the control group,MV titers were reduced in HPAEpiCs of the pre-infection group treated with anti-CD46 and anti-Nectin-4 respectively (48.03% and 49.53%).Furthermore,virus titers showed a more reduction in which treated with anti-CD46 and anti-Nectin-4 antibodies (27.15%,P<0.01).Western blot and Real-time PCR showed that anti-CD46 antibody and anti-Nectin-4 antibodies decreased the rate of MV infection.In the 2 h-infection group,however,the treatment with anti-CD46 and anti-Nectin-4 could significantly reduce the MV titer and NP protein in HPAEpiCs.The Co-IP assay showed that there were interaction between CD46 and Nectin-4.Conclusion: CD46 and Nectin-4 mediated MV infecting HPAEpiCs.Moreover,CD46 and Nectin-4 may play a synergetic role in MV infection,which could enhance the infection effect.
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Objective To investigate the expressions and the clinical significance of nectin-4 in pancreatic carcinoma and the relationship with clinicopathological features. Methods Immunohistocbemical techniques were used to detect nectin-4 expression in pancreatic carcinoma tissues (n = 40) and normal pancreatic tissues (n = 12 ), and the relationship between the expressions and clinicopathological parameters was analyzed. Results The IOD and area of nectin-4 were 2. 43 ± 0.75 and 9. 73 ± 1.86 in pancreatic carcinoma tissues, which were significantly higher than those in the normal pancreatic tissues( P ＜ 0.01 ).The expression of nectin-4 was not correlated with patients demographics ( P ＞ 0.05 ), and the protein expression was correlated with histopathologic grade ( P ＜ 0.01 ) and lymph metastasis ( P ＜ 0.05 ).Conclusions The high expression of nectin-4 in pancreatic carcinoma tissues suggests that its high expression may be correlated with the malignant degree of the carcinoma. nectin-4 can be considered as a reference index of differentiation, metastasis and prognosis in pancreatic carcinoma.