RPS6亚基肽段抑制S180肿瘤细胞的分子机制  

The molecular mechanism of RPS6 subunit peptide segment inhibiting S180 tumor cells

作　　者：蒲帝宏 叶姿妤 周丽倩 刘欣岚 鲁艳 侯怡铃[1] 丁祥 PU Dihong;YE Ziyu;ZHOU Liqian;LIU Xinlan;LU Yan;HOU Yiling;DING Xiang(Sichuan Provincial Collaborative Innovation Center of Tissue Repair Materials Engineering Technology,College of Life Sciences,China West Normal University,Nanchong 637009,China;College of Environmental Science and Engineering,China West Normal University,Nanchong 637009,China)

机构地区：[1]西华师范大学生命科学学院,四川省组织修复材料工程技术协同创新中心,南充637009 [2]西华师范大学环境科学与工程学院,南充637009

出　　处：《生物学杂志》2024年第2期32-38,共7页Journal of Biology

基　　金：四川省科技厅应用基础项目(2022NSFSC0107);四川省科技厅科技成果转化项目(2022NZZJ0003)。

摘　　要：为探究核糖体蛋白RPS6亚基肽段对S180肿瘤细胞基因表达的影响及抑制肿瘤细胞的关键分子和信号通路,以S180荷瘤小鼠为模型,用RPS6亚基肽段处理S180荷瘤小鼠,对S180肿瘤细胞进行Illumina测序获得差异表达的基因,并对这些差异基因进行GO和KEGG分析。基因表达结果显示,RPS6亚基肽段会导致mt-Cytb、mt-Nd1、Rpl13基因表达降低,阻碍S180肿瘤细胞的氧化磷酸化过程。GO分析结果显示,RPS6亚基肽段抑制肿瘤细胞关键门类集中于质膜和质膜外侧组成成分的变化及免疫反应调节和免疫细胞的激活。差异基因结果显示,RPS6亚基肽段通过增强PRL/PRLR信号,上调Uchl1基因表达,诱导肿瘤细胞周期停滞。KEGG通路富集分析结果显示,穿孔素(PRF1)和颗粒酶B(GZMB)表达诱导细胞凋亡,同时自然杀伤细胞(natural killer cell,NK)介导的细胞毒性与NF-κB信号通路信号增强,IFN-γ和TNF-α表达上调共同参与RPS6亚基肽段作用下的S180肿瘤细胞凋亡,抑制S180肿瘤细胞增殖。RPS6亚基肽段导致S180肿瘤细胞细胞周期停滞,并诱导自然杀伤细胞介导的细胞毒性及NF-κB信号通路的上调导致S180肿瘤细胞凋亡,为RPS6亚基肽段在抗肿瘤研究的应用提供一定的理论依据。To explore the effect of ribosomal protein RPS6 subunit peptide on S180 tumor cell gene expression and the key molecule and signal pathway of inhibiting tumor cells,using S180 tumor bearing mice as models,S180 tumor bearing mice were treated with RPS6 subunit peptide,and S180 tumor cells were sequenced by Illumina to obtain differentially expressed genes,and these differentially expressed genes were analyzed by GO and KEGG.Gene expression results showed that RPS6 subunit peptide could reduce the expression of mt-Cytb,mt-Nd1 and Rpl13 genes,and hinder the oxidative phosphorylation process of S180 tumor cells.The results of GO analysis showed that the key categories of RPS6 subunit peptide inhibiting tumor cells focused on the changes of plasma membrane and its outer components,and the regulation of immune response and the activation of immune cells.The differential gene results showed that RPS6 subunit peptide could enhance PRL/PRLR signal,up regulate Uchl1 gene expression and induce tumor cell cycle arrest.The results of KEGG pathway enrichment showed that the expression of perforin encoded by Prf1 and granzyme B encoded by Gzmb,together with cytotoxicity mediated by natural killer cells,participated in S180 tumor cell apoptosis under the effect of RPS6 subunit peptide.Meanwhile,TNF-αexpression was up-regulated in NF-κB signal pathway,in coordination with up-regulated IFN-γin cell-mediated cytotoxicity pathway also jointly inhibiting the proliferation of S180 tumor cells.RPS6 subunit peptide led to cell cycle arrest of S180 tumor cells,induced cytotoxicity mediated by natural killer cells and up regulation of NF-κB signal pathway led to S180 tumor cell apoptosis,which provided a theoretical basis for the application of RPS6 subunit peptide in antitumor research.

关 键 词：核糖体蛋白RPS6 小分子多肽 RNA-Seq测序 差异表达基因 NF-κB信号通路 

分 类 号：Q527.2[生物学—生物化学] Q78[医药卫生—肿瘤] R73[医药卫生—临床医学]