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TRIM47过表达是一个不良预后因素,并且在非小细胞肺癌的致癌过程中起作用。

TRIM47 overexpression is a poor prognostic factor and contributes to carcinogenesis in non-small cell lung carcinoma.

作者信息

Han Yudong, Tian Haiying, Chen Pei, Lin Qiang

机构信息

Department of Thoracic Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

出版信息

Oncotarget. 2017 Apr 4;8(14):22730-22740. doi: 10.18632/oncotarget.15188.

Abstract

Non-small cell lung carcinoma (NSCLC) is the most common malignancy with the highest morbidity and mortality. In this study, we found that tripartite motif containing 47 (TRIM47) expression level was higher in tumor tissues than in normal adjacent tissues. Overexpression of TRIM47 closely correlated with poor prognosis in patients with NSCLC. Multivariate Cox regression analyses showed that TRIM47 overexpression could be considered an independent prognostic factor for NSCLC. TRIM47 depletion significantly inhibited cell proliferation and induced G1phase arrest in A549 and H358 cell lines. Moreover, TRIM47 silencing remarkably inhibited cell migration, cell invasion, and tumorigenicity in nude mice. Gene set enrichment analysis (GSEA) revealed that cancer-related process and pathways, including p53-cell cycle and NFκB-epithelial mesenchymal transition (EMT) pathway, were significantly correlated with TRIM47 expression. Real-time PCR and Western blot analysis revealed that TRIM47 exerts an inhibitory effect on p53 and an facilitatory effect on NF-κB, thereby promoting tumor proliferation and metastasis. Taken together, TRIM47 acts as a tumor oncogene in NSCLC. Our data provide insight into the possible biological mechanism of TRIM47 in the progression of NSCLC and highlight its usefulness as a potential therapeutic target.

摘要

非小细胞肺癌(NSCLC)是最常见的恶性肿瘤,其发病率和死亡率最高。在本研究中,我们发现含三联基序蛋白47(TRIM47)在肿瘤组织中的表达水平高于相邻正常组织。TRIM47的过表达与NSCLC患者的不良预后密切相关。多因素Cox回归分析表明,TRIM47过表达可被视为NSCLC的独立预后因素。TRIM47缺失显著抑制A549和H358细胞系的细胞增殖并诱导G1期阻滞。此外,TRIM47沉默显著抑制裸鼠的细胞迁移、细胞侵袭和致瘤性。基因集富集分析(GSEA)显示,包括p53-细胞周期和NFκB-上皮间质转化(EMT)途径在内的癌症相关过程和通路与TRIM47表达显著相关。实时PCR和蛋白质印迹分析表明,TRIM47对p53发挥抑制作用,对NF-κB发挥促进作用,从而促进肿瘤增殖和转移。综上所述,TRIM47在NSCLC中作为肿瘤癌基因发挥作用。我们的数据为TRIM47在NSCLC进展中的可能生物学机制提供了见解,并突出了其作为潜在治疗靶点的有用性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/618f/5410258/5122d34acd6a/oncotarget-08-22730-g001.jpg

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