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肺癌新型治疗靶点的鉴定:线粒体核糖体蛋白L9

Identification of a novel therapeutic target for lung cancer: Mitochondrial ribosome protein L9.

作者信息

Li Xin-Yuan, He Xin-Yu, Zhao Hong, Qi Lu, Lu Jin-Jian

机构信息

State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China.

The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310006, China.

出版信息

Pathol Res Pract. 2023 Aug;248:154625. doi: 10.1016/j.prp.2023.154625. Epub 2023 Jun 16.

Abstract

Lung cancer has a high fatality rate and incidence rate. At present, the initial and progress mechanism of lung cancer has not been completely elucidated and new therapeutic targets still need to be developed. In this study, the screening process was based on lung cancer expression profile data and survival analysis. Mitochondrial ribosome protein L9 (MRPL9) was upregulated in lung cancer tissues and related to the poor overall survival rate and recurrence-free survival rate of lung cancer patients. Knockdown of MRPL9 inhibited the proliferation, sphere-formation, and migration ability of lung cancer cells. MRPL9 was associated with the c-MYC signaling pathway, and lung cancer patients with high expression of both MRPL9 and MYC had a poor prognosis. Furthermore, c-MYC was associated with the epithelial-mesenchymal transition (EMT) regulatory protein zinc finger E-box binding homeobox 1 (ZEB1) by bioinformatics analysis. The relationship between ZEB1 and c-MYC was further confirmed by interfering with c-MYC expression. MRPL9 is a potential therapeutic target for lung cancer and exerts its biological functions by affecting the transcription factor c-MYC thereby regulating the EMT regulator ZEB1.

摘要

肺癌具有较高的死亡率和发病率。目前,肺癌的起始和进展机制尚未完全阐明,仍需开发新的治疗靶点。在本研究中,筛选过程基于肺癌表达谱数据和生存分析。线粒体核糖体蛋白L9(MRPL9)在肺癌组织中上调,且与肺癌患者较差的总生存率和无复发生存率相关。敲低MRPL9可抑制肺癌细胞的增殖、成球能力和迁移能力。MRPL9与c-MYC信号通路相关,MRPL9和MYC均高表达的肺癌患者预后较差。此外,通过生物信息学分析发现c-MYC与上皮-间质转化(EMT)调节蛋白锌指E盒结合同源框1(ZEB1)相关。通过干扰c-MYC表达进一步证实了ZEB1与c-MYC之间的关系。MRPL9是肺癌的一个潜在治疗靶点,它通过影响转录因子c-MYC发挥其生物学功能,从而调节EMT调节因子ZEB1。

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