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[MRPL13高表达通过抑制p53信号通路促进胃癌细胞的细胞周期进程和增殖,影响长期预后]

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

作者信息

Wang L, Xia Y, Zhang Z, Liu X, Shi J, Wang Y, Li J, Zhnag X, Geng Z, Song X, Zuo L

机构信息

Department of Gastrointestinal Surgery, First Affiliated Hospital of Bengbu Medical College, Bengbu 233004, China.

Bengbu Medical College, Bengbu 233030, China.

出版信息

Nan Fang Yi Ke Da Xue Xue Bao. 2023 Sep 20;43(9):1558-1566. doi: 10.12122/j.issn.1673-4254.2023.09.13.

DOI:10.12122/j.issn.1673-4254.2023.09.13
PMID:37814870
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10563107/
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 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 (<0.05) and positively correlated with peripheral blood Ki67, CEA and CA19-9 levels (<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% : 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 (<0.05), and MRPL13 knockdown produced the opposite effects (<0.05). MRPL13 overexpression significantly promoted gastric cancer cell xenograft growth (<0.05), and MRPL13 knockdown obviously inhibited tumor growth in nude mice (<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 (<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.

摘要

目的

检测线粒体核糖体蛋白L13(MRPL13)在胃癌中的表达情况及其对长期预后的影响,并探讨其可能机制。

方法

基于公共癌症数据库分析MRPL13在胃癌中的表达水平及其与患者预后的关系,同时分析2014年1月至2017年10月在我院接受根治性胃切除术的100例胃癌患者的数据。进一步评估MRPL13过表达和敲低对胃癌MGC-803和SGC-7901细胞增殖、细胞周期以及对裸鼠皮下异种移植瘤生长的影响。

结果

生物信息学分析和患者数据均显示,MRPL13在胃癌中的表达水平显著高于癌旁组织(<0.05),且与外周血Ki67、CEA和CA19-9水平呈正相关(<0.05)。MRPL13高表达是影响胃癌患者5年生存率的独立危险因素(HR:3.284;95%:1.537 - 7.016)。基因集富集分析表明,MRPL13参与细胞周期和p53信号通路。在培养的胃癌细胞中,MRPL13过表达显著促进细胞增殖、G1/S期转换以及细胞周期蛋白D1和细胞周期蛋白依赖性激酶6的表达(<0.05),而MRPL13敲低则产生相反作用(<0.05)。MRPL13过表达显著促进胃癌细胞异种移植瘤生长(<0.05),而MRPL13敲低明显抑制裸鼠肿瘤生长(<0.05)。在培养的胃癌细胞和裸鼠异种移植瘤中,MRPL13过表达显著降低而MRPL13敲低增强p53和p21的表达(<0.05)。

结论

MRPL13在胃癌中高表达,可能通过抑制p53信号通路促进癌细胞增殖和细胞周期进程,从而影响患者的长期预后。

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