RIPK4通过调控NF-КB参与TNFα信号通路从而促进卵巢癌细胞增殖和迁移  

RIPK 4 participates in TNFαsignaling pathway by regulating NF-КB to promote ovarian cancer cell proliferation and migration

作　　者：熊焰[1] 梁承蓉[1] 邵安娜[1] XIONG Yan;LIANG Chengrong;SHAO Anna(Department of Obstetrics and Gynecology,Second People's Hospital of Jingzhou City,Jingzhou Hubei 434000,P.R.China)

机构地区：[1]荆州市第二人民医院妇产科,湖北荆州434000

出　　处：《中国计划生育和妇产科》2020年第8期62-66,70,共6页Chinese Journal of Family Planning & Gynecotokology

摘　　要：目的筛选卵巢癌中具有临床意义的潜在药物靶点,研究其在卵巢癌发生发展中的生物学功能和分子机制。方法通过临床数据库GEPIA筛选目的靶基因,分别敲低和过表达目的基因,利用细胞增殖实验和划痕迁移实验验证目的基因在卵巢癌发生发展中的作用;探索目的基因在卵巢癌中发挥功能的潜在分子机制,并通过蛋白免疫印迹实验进行验证。结果共有18个基因在卵巢癌中高表达,且具有显著临床预后相关性;与正常组织相比,受体相互作用蛋白激酶4(receptor-interacting protein kinase 4,RIPK 4)在卵巢癌中显著高表达,且高表达的患者预后不良;敲低RIPK 4显著抑制卵巢癌细胞的生长增殖和迁移,过表达RIPK 4显著促进卵巢癌细胞的生长增殖和迁移;敲低RIPK 4显著减少核因子КB(nuclear factor-Кgene binding,NF-КB)的入核并抑制其下游靶基因的表达;过表达RIPK 4显著增加NF-КB的入核并促进其下游靶基因的表达,由此初步证明了RIPK 4可能参与NF-КB介导的α肿瘤坏死因子(tumor necrosis factorα,TNFα)信号通路。结论RIPK 4高表达增加NF-КB的入核并显著促进其下游靶基因的高表达,从而参与NF-КB介导的TNFα信号通路从而促进卵巢癌细胞生长增殖和迁移。Objective To screen potential drug targets of clinical significance in ovarian cancer,and study their biological functions and molecular mechanisms in the development of ovarian cancer.Methods Target genes were screened by clinical database GEPIA.The target gene was knocked down and over-expressed.Cell proliferation experiments and migration experiments were used to verify the role of the target gene in the development of ovarian cancer.Explored the potential molecular mechanism of the target gene's function in ovarian cancer,and verified it by Western blotting and qPCR.Results A total of 18 genes were highly expressed in ovarian cancer and had significant clinical prognostic relevance;compared with normal tissues,RIPK 4 was significantly over-expressed in ovarian cancer,and patients with high expression had a poor prognosis;Knockdown of RIPK 4 significantly inhibited the growth,proliferation and migration of ovarian cancer cells,and over-expression of RIPK 4 significantly promoted the growth,proliferation and migration of ovarian cancer cells;knockdown of RIPK 4 significantly reduced the nucleation of NF-κB and inhibited the expression of downstream target genes;over-expression RIPK 4 significantly increased the nuclear entry of NF-κB and promoted the expression of its downstream target genes,thus preliminarily proving that RIPK 4 may participate in the NF-κB-mediated TNFαsignaling pathway.Conclusion The high expression of RIPK 4 increases the nuclear entry of NF-κB and significantly promotes the high expression of its downstream target genes,thereby participating in the NF-κB-mediated TNFαsignaling pathway and promoting the growth,proliferation and migration of ovarian cancer cells.

关 键 词：卵巢癌 RIPK 4 NF-КB 靶基因 分子机制 

分 类 号：R737.31[医药卫生—肿瘤]