南方医科大学学报

南方医科大学学报 ›› 2023, Vol. 43 ›› Issue (9): 1558-1566.doi: 10.12122/j.issn.1673-4254.2023.09.13

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高表达MRPL13促进胃癌细胞增殖并影响患者预后：基于抑制p53信号

王 炼，夏勇生，张 震，刘馨悦，施金冉，王月月，李 静，张小凤，耿志军，宋 雪，左芦根   

  1. 蚌埠医学院第一附属医院胃肠外科，检验科，中心实验室，安徽 蚌埠 233004；蚌埠医学院，安徽 蚌埠 233030；组织移植安徽省重点实验室，安徽 蚌埠 233030；炎症相关性疾病基础与转化研究安徽省重点实验室，安徽 蚌埠 233030
  • 出版日期:2023-09-20 发布日期:2023-09-28

High expression of MRPL13 promotes cell cycle progression and proliferation of gastric cancer cells by inhibiting p53 signaling to affect long-term prognosis

WANG Lian, XIA Yongsheng, ZHANG Zhen, LIU Xinyue, SHI Jinran, WANG Yueyue, LI Jing, ZHNAG Xiaofeng, GENG Zhijun, SONG Xue, ZUO Lugen   

  1. Department of Gastrointestinal Surgery, Clinical Laboratory, Central Laboratory, First Affiliated Hospital of Bengbu Medical College, Bengbu 233004, China; Bengbu Medical College, Bengbu 233030, China; Anhui Provincial Key Laboratory of Tissue Transplantation, Bengbu Medical College, Bengbu 233030, China; Anhui Province Key Laboratory of Basic and Translational Research of Inflammation-related Diseases, Bengbu 233030, China
  • Online:2023-09-20 Published:2023-09-28

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摘要： 目的 明确线粒体核糖体蛋白L13（MRPL13）在胃癌中的表达情况及对预后的影响，并分析其可能的作用机制。方法 利用公共肿瘤数据库，对胃癌中MRPL13的表达及对预后的作用及发生机理进行初步分析。进一步纳入我院2014年1月~2017年10月开展胃癌根治术的100例患者，分析MRPL13表达量对肿瘤进展及术后5年生存期的影响。体外采用慢病毒转染的方式调控胃癌细胞系（MGC-803和SGC-7901）中MRPL13的表达，分析其对细胞增殖和周期的影响。通过裸鼠皮下移植瘤模型进一步验证MRPL13在体内对肿瘤生长的影响。结合体内外研究分析MRPL13影响胃癌细胞的分子机理。结果 生物信息学和本机构的病例分析发现，胃癌组织中MRPL13的水平均显著高于癌旁组织（P<0.05）。相关性分析表明，MRPL13的表达与Ki67、外周血CEA和CA19-9均呈正相关（P<0.05）。单因素结合Cox多因素分析，证实MRPL13高表达是影响胃癌5年生存率的独立危险因素（HR：3.284；95% CI：1.537~7.016）。富集分析提示MRPL13的功能可能和细胞周期、p53信号有关。体外CCK-8、克隆形成、流式细胞术和免疫印迹检测显示：上调MRPL13促进胃癌细胞增殖、G1/S期转化和细胞周期蛋白（CyclinD1和CDK6）表达（P<0.05），下调MRPL13的结果则与之相反（P<0.05）。在体研究显示：上调胃癌细胞MRPL13表达显著促进裸鼠移植瘤的生长（P<0.05），而下调则抑制（P<0.05）。机制分析显示，上调MRPL13抑制胃癌细胞和裸鼠移植瘤中p53和p21的表达（P<0.05），而下调则反之（P<0.05）。结论 MRPL13在胃癌中表达升高且影响长期预后，其可能通过抑制p53信号促进胃癌细胞增殖和细胞周期进程。

关键词: 胃癌, 线粒体核糖体蛋白L13, 预后, 细胞周期, p53

Abstract: Objective To determine the expression of mitochondrial ribosomal protein L13 (MRPL13) in gastric cancer and its impact on long-term prognosis and explore the possible mechanism. Methods We analyzed MRPL13 expression level in gastric cancer and its association with the patients' prognosis based on the public cancer database the data of 100 gastric cancer patients undergoing radical gastrectomy in our hospital from January, 2014 to October, 2017. We further assessed the effects of MRPL13 overexpression and knockdown on proliferation and cell cycle of gastric cancer MGC-803 and SGC-7901 cells in vitro and on subcutaneous xenograft growth in nude mice. Results Both bioinformatic analysis and the patients' data demonstrated that the expression level of MRPL13 was significantly higher in gastric cancer than in adjacent tissues (P<0.05) and positively correlated with peripheral blood Ki67, CEA and CA19-9 levels (P<0.05). High expression of MRPL13 was an independent risk factor affecting the 5-year survival rate of gastric cancer patients (HR: 3.284; 95% CI: 1.537-7.016). Gene set enrichment analysis suggested that MRPL13 was involved in cell cycle and p53 signaling. In cultured gastric cancer cells, MRPL13 overexpression significantly promoted cell proliferation, G1/S phase transition and the expressions of cyclin D1 and CDK6 (P<0.05), and MRPL13 knockdown produced the opposite effects (P<0.05). MRPL13 overexpression significantly promoted gastric cancer cell xenograft growth (P<0.05), and MRPL13 knockdown obviously inhibited tumor growth in nude mice (P<0.05). In both cultured gastric cancer cells and the xenografts in nude mice, MRPL13 overexpression significantly decreased while MRPL13 knockdown enhanced the expressions of p53 and p21 (P<0.05). Conclusion MRPL13 is highly expressed in gastric cancer and affects the long- term prognosis of the patients possibly by inhibiting p53 signaling to promote cancer cell proliferation and cell cycle progression.

Key words: gastric cancer, mitochondrial ribosomal protein L13, prognosis, cell cycle, p53