FAM84B抑制p53通路对食管鳞癌细胞增殖作用的影响  

Effect of inhibition of p53 pathway by FAM84B on proliferation of esophageal squamous cell carcinoma cells

作　　者：陈菲[1] 张亚玲 王芳[3] 李泓漪 周延 翁泳佳 程彩霞[2] CHEN Fei;ZHANG Yaling;WANG Fang;LI Hongyi;ZHOU Yan;WENG Yongjia;CHENG Caixia(Shanxi Medical University,Taiyuan 030001,Shanxi Province,China;不详)

机构地区：[1]山西医科大学,山西太原030001 [2]山西医科大学第一医院,山西太原030001 [3]山西医科大学转化医学中心,山西太原030010

出　　处：《中国生物制品学杂志》2023年第7期775-780,共6页Chinese Journal of Biologicals

基　　金：国家自然科学基金青年基金(81602458);山西医科大学科技创新基金(01201505)。

摘　　要：目的 研究食管鳞癌(esophageal squamous cell carcinoma,ESCC)中FAM84B的表达情况,及其通过p53通路对细胞生长的调控机制。方法 收集中国食管癌高发区山西省肿瘤医院及新疆医科大学附属肿瘤医院共508份ESCC肿瘤样本及其邻近正常组织样本,进行全基因组测序(whole genome sequencing,WGS)和外显子测序(whole exome sequencing,WES),筛选出拷贝数明显扩增的FAM84B基因。在高表达FAM84B的ESCC细胞系KYSE150中,用小干扰RNA感染法干扰FAM84B后,采用MTT和硬克隆形成试验检测FAM84B对细胞生长的影响;在低表达FAM84B ESCC细胞系KYSE450中,用质粒pCMV-3×flag-FAM84B过表达FAM84B后,采用MTT和硬克隆形成试验检测FAM84B对细胞生长的影响。采用Western blot法检测敲低FAM84B表达对细胞周期蛋白CDK4、CDK6和CCND1表达的影响。结果 对508份ESCC石蜡切片进行WGS,发现109份FAM84B基因拷贝数扩增(21.45%);FAM84B基因存在于8q24.21附近,并且存在1个显著放大的病灶峰。敲低FAM84B抑制ESCC细胞增殖,过表达FAM84B促进ESCC增殖。FAM84B低表达促进p53介导的细胞周期进行。结论 FAM84B通过抑制ESCC细胞p53通路蛋白的表达,促进细胞周期由G1期向S期转化,进而促进细胞增殖。Objective To study the expression of FAM84B in esophageal squamous cell carcinoma(ESCC) and its regulatory mechanism on cell growth by p53 pathway.Methods A total of 508 ESCC tumor samples and their adjacent normal tissue samples were collected from Shanxi Cancer Hospital and Affiliated Cancer Hospital of Xinjiang Medical University,which are high incidence areas of ESCC in China.Using whole genome sequencing(WGS) and whole exome sequencing(WES),FAM84B gene with significantly amplified copy number were screened.In ESCC cell line KYSE150with high expression of FAM84B,the effect of FAM84B on cell growth was detected by MTT and hard clone formation assay after interfering with FAM84B by small interfering RNA infection;In ESCC cell line KYSE450 with low expression of FAM84B,FAM84B was overexpressed with plasmid pCMV-3 ×flag-FAM84B,and the effect of FAM84B on cell growth was detected by MTT and hard clone formation assay.The effects of FAM84B knock-down on the expression of CDK4,CDK6and CCND1 were detected by Western blot.Results WGS analysis of 508 ESCC paraffin sections showed 109 cases of FAM84B copy number amplification(21.45%);FAM84B gene existed near 8q24.21 and was a significantly enlarged lesion peak.Knockdown of FAM84B inhibited the proliferation of ESCC cells,while overexpression of FAM84B promoted that.The low expression of FAM84B promoted the cell cycle progression mediated by p53.Conclusion FAM84B can promote cell proliferation by promoting the cell cycle transition from G1 phase to S phase via inhibiting the expression of p53 pathway proteins in ESCC cells.

关 键 词：食管鳞癌 FAM84B P53 细胞周期 细胞增殖 

分 类 号：R3[医药卫生—基础医学]