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慢病毒载体介导的RBM5过表达下调人非小细胞肺癌细胞中的表皮生长因子受体(EGFR)表达。

Lentiviral vector-mediated RBM5 overexpression downregulates EGFR expression in human non-small cell lung cancer cells.

作者信息

Su Zhenzhong, Yin Jinzhi, Zhao Lijing, Li Ranwei, Liang Hong, Zhang Jie, Wang Ke

机构信息

Department of Respiratory Medicine, The Second Affiliated Hospital of Jilin University, No,218 Ziqiang Street, Nanguan District, Changchun, Jilin 130041, China.

出版信息

World J Surg Oncol. 2014 Dec 2;12:367. doi: 10.1186/1477-7819-12-367.

Abstract

BACKGROUND

RNA binding motif 5 (RBM5) is a tumor suppressor gene that modulates apoptosis through the regulation of alternative splicing of apoptosis-related genes. Our previous studies suggested that RBM5 expression was negatively correlated with the expression of epidermal growth factor receptor (EGFR) in non-small cell lung cancer (NSCLC) tissues. This study was aimed at determining whether RBM5 is able to regulate EGFR expression.

METHODS

Both in vitro and in vivo studies were carried out to determine the effect of RBM5 on the expression of EGFR. Lentiviral vector-mediated RBM5 overexpression was employed in lung adenocarcinoma cell line A549. A549 xenograft mice were treated with recombinant RBM5 plasmid carried by attenuated Salmonella typhi Ty21a. Real-time quantitative polymerase chain reaction and Western blot were carried out to detect RBM5 and EGFR expression.

RESULTS

Both in vivo and in vitro studies indicated that the expression of EGFR mRNA and protein was decreased significantly in the RBM5 overexpression group compared to control groups as shown by real-time PCR and Western blot analysis. We identified that RBM5 overexpression inhibited EGFR expression both in A549 cells and in A549 xenograft mice model.

CONCLUSIONS

Our study demonstrated that EGFR expression is regulated by RBM5 in lung adenocarcinomas cells either in a direct or indirect way, which might be meaningful with regards to target therapy in lung cancer.

摘要

背景

RNA结合基序5(RBM5)是一种肿瘤抑制基因,通过调节凋亡相关基因的可变剪接来调控细胞凋亡。我们之前的研究表明,在非小细胞肺癌(NSCLC)组织中,RBM5的表达与表皮生长因子受体(EGFR)的表达呈负相关。本研究旨在确定RBM5是否能够调节EGFR的表达。

方法

进行了体外和体内研究,以确定RBM5对EGFR表达的影响。在肺腺癌细胞系A549中采用慢病毒载体介导的RBM5过表达。用减毒伤寒沙门氏菌Ty21a携带的重组RBM5质粒处理A549异种移植小鼠。采用实时定量聚合酶链反应和蛋白质免疫印迹法检测RBM5和EGFR的表达。

结果

体内和体外研究均表明,与对照组相比,RBM5过表达组中EGFR mRNA和蛋白的表达通过实时PCR和蛋白质免疫印迹分析显著降低。我们发现RBM5过表达在A549细胞和A549异种移植小鼠模型中均抑制EGFR表达。

结论

我们的研究表明,RBM5在肺腺癌细胞中以直接或间接的方式调节EGFR表达,这对于肺癌的靶向治疗可能具有重要意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27a7/4289049/05d2f516f6c1/12957_2014_1844_Fig1_HTML.jpg

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