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沉默调节蛋白6通过B细胞淋巴瘤2调节肾透明细胞癌细胞的增殖和存活。

Sirtuin 6 regulates the proliferation and survival of clear cell renal cell carcinoma cells via B-cell lymphoma 2.

作者信息

An Jun, Yang Jieping, Yao Yang, Lu Kaining, Zhao Zhiqiang, Yu Meng, Zhu Yuyan

机构信息

Department of Urology, The First Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China.

Department of Physiology, Shenyang Medical College, Shenyang, Liaoning 110034, P.R. China.

出版信息

Oncol Lett. 2021 Apr;21(4):293. doi: 10.3892/ol.2021.12554. Epub 2021 Feb 17.

Abstract

Sirtuin 6 () is a member of the third family of longevity proteins (SIRTs) that is involved in the development of different types of cancer. However, the potential role of in clear cell renal cell carcinoma (ccRCC) and its molecular mechanism have not yet been fully elucidated. Therefore, the present study aimed to investigate the association between SIRT6 and ccRCC, and to further examine the underlying mechanism of its effect on ccRCC proliferation, using bioinformatics analysis, and and experiments. The results of the present study demonstrated that was upregulated in ccRCC tissues. In addition, bioinformatics analysis revealed that high expression was closely associated with poor prognosis of patients with ccRCC. experiments demonstrated that silencing expression in ccRCC-derived 769-P and 786-O cells significantly inhibited their proliferation, migration and invasion. Consistent with these results, assays demonstrated that knockdown markedly attenuated tumor growth arising from 769-P cells. Furthermore, depletion of enhanced the sensitivity of ccRCC cells to cisplatin. Notably, silencing expression decreased B-cell lymphoma 2 (Bcl-2) expression and increased Bax expression, respectively. Taken together, these results suggest that acts as a proto-oncogene in ccRCC through the augmentation of the Bcl-2-dependent pro-survival pathway, and may be used as a therapeutic target for patients with ccRCC.

摘要

沉默调节蛋白6(Sirtuin 6,SIRT6)是长寿蛋白(SIRTs)第三家族的成员,参与不同类型癌症的发生发展。然而,SIRT6在肾透明细胞癌(ccRCC)中的潜在作用及其分子机制尚未完全阐明。因此,本研究旨在通过生物信息学分析以及细胞实验和动物实验,探讨SIRT6与ccRCC的关系,并进一步研究其影响ccRCC增殖的潜在机制。本研究结果表明,SIRT6在ccRCC组织中表达上调。此外,生物信息学分析显示,SIRT6高表达与ccRCC患者的不良预后密切相关。细胞实验表明,沉默ccRCC来源的769-P和786-O细胞中的SIRT6表达可显著抑制其增殖、迁移和侵袭。与这些结果一致,动物实验表明,敲低SIRT6可显著减弱769-P细胞引起的肿瘤生长。此外,SIRT6缺失增强了ccRCC细胞对顺铂的敏感性。值得注意的是,沉默SIRT6表达分别降低了B细胞淋巴瘤2(Bcl-2)的表达并增加了Bax的表达。综上所述,这些结果表明,SIRT6通过增强Bcl-2依赖性促生存途径在ccRCC中发挥原癌基因作用,可能作为ccRCC患者的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/64db/7905630/2cee16c2ef98/ol-21-04-12554-g00.jpg

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