Effect Of PDCD11 On Bioethology Of Hepatocellular Carcinoma And Its Mechanism

Background and Objective:Liver cancer is a kind of liver cancer with high incidence and great harm.Tumor is one of the main causes of tumor death,and its incidence is increasing year by year.Primary liver cancer(HCC)is the most common kind of liver cancer in clinic,which is often accompanied by chronic liver disease.Unfortunately,at the current level,Clinically,due to the pathological characteristics of liver cancer,the treatment of middle and advanced liver cancer is limited,and the curative effect is not good.Although the research on liver cancer has made great progress in the past few decades,there are still many deficiencies.At present,more than 200 genes closely related to the prognosis of hepatocellular carcinoma have been reported.However,the biomarkers and drug targets that can be found are still very limited.Therefore,looking for biomarkers for early diagnosis of HCC can bring better treatment and prognosis for patients.PDCD11 is an important protein closely related to tumorigenesis and development.Not long ago Recent studies have shown that PDCD11 is closely related to the progression of many cancers.However,there are no studies on the relationship between PDCD11 and hepatocellular carcinoma.Through bioinformatics technology,Our previous work found that PDCD11 was highly expressed in hepatocellular carcinoma.There is a high level in the tissues of patients with liver cancer,and it is closely related to the prognosis of patients.We believe that PDCD11 can be used as a potential candidate gene.It plays an important regulatory role in the progression of liver cancer.In addition,it has been reported that PDCD11 can bind to p65 and activate NF-κB.Signal pathways cause changes in the physiological activities of cells and the function of molecules.Based on this,we propose the hypothesis that PDCD11 plays an important role in the NF-κB signal pathway.Relationship between NF-κB signal transduction pathway and primary hepatocellular carcinoma.We did the following experiments to test this hypothesis:Methods:1.HCCLM3 and MHCC97 H cell lines were used to construct stable interference cell lines,and the cell lines with the best interference effect were selected by Western blot and q RT-PCR experiments.2.The expression and prognosis of PDCD11 in patients with HCC were studied by using TCGA and ICGC database,and the correlation between PDCD11 expression and clinical indexes was analyzed.3.Western blot and q RT-PCR methods were used to study the role of PDCD11 in HCC cells.Firstly,HCC cells were cultured in vitro by CCK8,plate cloning and EDU methods,and their growth was observed.Then Scratch and Transwell experiments were used to observe the infiltration and metastasis of HCC;in vivo,we used lentivirus to establish a new The effect of PDCD11 on the tumorigenesis ability of PDCD11 nude mice was studied by constructing the tumor formation experiment in vivo Diffuse.4.Apoptosis-related indexes were detected by Western blot technique.5.To explore the molecular mechanism of PDCD11 regulating hepatocellular carcinoma by mediating NF-κB signal pathway by Western blot.Results:1.By analyzing the transcriptome data of patients with hepatocellular carcinoma in TCGA and ICGC database,Our group found that PDCD11 was significantly increased in liver cancer,and positively correlated with the prognosis of patients with liver cancer.PDCD11 may be an independent prognostic factor in patients with hepatocellular carcinoma.2.Through Western blot assay,Compared with normal hepatocytes,the expression of PDCD11 in HCC was significantly increased.After knockout of PDCD11,plate cloning,CCK8 and EDU significantly inhibited the growth of HCC cells.The results showed that it had a certain effect on the infiltration and metastasis of HCC.Compared with the control group,the tumor volume,mass and fluorescence intensity of LV-sh PDCD11 group decreased.3.After interfering with the expression of PDCD11,the results of apoptosisrelated proteins found by Western blot assay suggest that apoptosis has been inhibited.4.We found that PDCD11 can directly bind to p65,thus activating the NF-κB pathway affects the biological behavior and molecular function of hepatocellular carcinoma cells.Conclusions:Bioinformatics analysis showed that the expression of PDCD11 in HCC was significantly higher than that in corresponding HCC tissues,Moreover,the prognosis of patients with high expression was poor.PDCD11 has a significant effect on the proliferation,invasion and metastasis of HCC cells.Through WB experiment,it was found that interfering with the expression of PDCD11 could increase the expression of Bcl2 and decrease the protein levels of Bax and C-caspase3.The results suggested that the apoptosis was inhibited after interfering with the expression of PDCD11.PDCD11 can directly bind to p65,thus activating the NF-κB pathway to affect the biological behavior and molecular function of hepatocellular carcinoma cells.This finding preliminarily reveals that PDCD11 can be a potential target and prognostic biomarker for hepatocellular carcinoma,and is of great significance for the treatment of hepatocellular carcinoma.