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定量蛋白质组学分析揭示了长链非编码RNA Ftx在促进胃癌进展中的潜在作用。

Quantitative Proteomics Analysis Revealed the Potential Role of lncRNA Ftx in Promoting Gastric Cancer Progression.

作者信息

Zhu Lihui, Jia Ruzhen, Zhang Junyong, Li Xiao, Qin Chengyong, Zhao Qi

机构信息

Department of Gastroenterology, Shandong Provincial Hospital affiliated to Shandong University, Jinan, 250021, P. R. China.

Department of Gastroenterology, Shandong Provincial Hospital affiliated to Shandong First Medical University, Jinan, 250021, P. R. China.

出版信息

Proteomics Clin Appl. 2020 Jan;14(1):e1900053. doi: 10.1002/prca.201900053. Epub 2019 Nov 25.

Abstract

PURPOSE

The molecular pathogenesis of gastric cancer is still ambiguous till now. Here, it is demonstrated that long noncoding RNA (lncRNA) Ftx acts as a novel tumor promotor of gastric cancer and a potent regulator of hexokinase-2 (HK2).

EXPERIMENTAL DESIGN

The role of lncRNA Ftx is detected in the loss and gain-of-function models of gastric cancer cells. Tandem mass tags combined with multidimensional LC and MS analyses are performed to decipher comparative proteomic profiles of gastric cancer cells in response to lncRNA Ftx knockdown and overexpression. Real-time roteomics-clinical applications (PCR) and western blot are used to validate the proteomic data.

RESULTS

A total of 5124 proteins are quantified and indicated in diverse biological functions and metabolic related signaling pathways. Interestingly, HK2, which is downregulated when lncRNA Ftx is deleted and upregulated while lncRNA Ftx is overexpressed, is further validated in gastric cancer cells.

CONCLUSIONS AND CLINICAL RELEVANCE

The present study suggests lncRNA Ftx promotes gastric cancer progression by upregulating HK2, which provides a new perspective for the mechanism of gastric cancer progression, and thus identifies potential therapeutic targets for gastric cancer.

摘要

目的

胃癌的分子发病机制至今仍不明确。在此,研究表明长链非编码RNA(lncRNA)Ftx作为一种新型的胃癌肿瘤促进因子以及己糖激酶-2(HK2)的有效调节因子。

实验设计

在胃癌细胞的功能缺失和功能获得模型中检测lncRNA Ftx的作用。采用串联质量标签结合多维液相色谱和质谱分析,以解析胃癌细胞在lncRNA Ftx敲低和过表达情况下的比较蛋白质组学图谱。运用实时定量蛋白质组学-临床应用(PCR)和蛋白质免疫印迹法验证蛋白质组学数据。

结果

共定量分析了5124种蛋白质,并表明它们参与了多种生物学功能和代谢相关信号通路。有趣的是,在胃癌细胞中进一步验证发现,当lncRNA Ftx缺失时HK2表达下调,而lncRNA Ftx过表达时HK2表达上调。

结论及临床意义

本研究表明lncRNA Ftx通过上调HK2促进胃癌进展,这为胃癌进展机制提供了新的视角,从而确定了胃癌潜在的治疗靶点。

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