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翻译起始因子eIF3b的沉默促进骨肉瘤细胞凋亡。

Silencing of translation initiation factor eIF3b promotes apoptosis in osteosarcoma cells.

作者信息

Choi Y J, Lee Y S, Lee H W, Shim D M, Seo S W

机构信息

Department of Orthopaedic Surgery, Samsung Medical Center, Sungkyunkwan University, 50, Ilwon-dong, Gangnam-gu, 135-710, Seoul, South Korea.

Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, 50, Ilwon-dong, Gangnam-gu, 135-710, Seoul, South Korea.

出版信息

Bone Joint Res. 2017 Mar;6(3):186-193. doi: 10.1302/2046-3758.63.BJR-2016-0151.R2.

Abstract

OBJECTIVES

Eukaryotic translation initiation factor 3 (eIF3) is a multi-subunit complex that plays a critical role in translation initiation. Expression levels of eIF3 subunits are elevated or decreased in various cancers, suggesting a role for eIF3 in tumorigenesis. Recent studies have shown that the expression of the eIF3b subunit is elevated in bladder and prostate cancer, and eIF3b silencing inhibited glioblastoma growth and induced cellular apoptosis. In this study, we investigated the role of eIF3b in the survival of osteosarcoma cells.

METHODS

To investigate the effect of eIF3b on cell viability and apoptosis in osteosarcoma cells, we first examined the silencing effect of eIF3b in U2OS cells. Cell viability and apoptosis were examined by the Cell Counting Kit-8 (CCK-8) assay and Western blot, respectively. We also performed gene profiling to identify genes affected by eIF3b silencing. Finally, the effect of eIF3b on cell viability and apoptosis was confirmed in multiple osteosarcoma cell lines.

RESULTS

eIF3b silencing decreased cell viability and induced apoptosis in U2OS cells, and by using gene profiling we discovered that eIF3b silencing also resulted in the upregulation of tumour necrosis factor receptor superfamily member 21 (TNFRSF21). We found that TNFRSF21 overexpression induced cell death in U2OS cells, and we confirmed that eIF3b silencing completely suppressed cell growth in multiple osteosarcoma cell lines. However, eIF3b silencing failed to suppress cell growth completely in normal fibroblast cells.

CONCLUSION

Our data led us to conclude that eIF3b may be required for osteosarcoma cell proliferation by regulating TNFRSF21 expression. Y. J. Choi, Y. S. Lee, H. W. Lee, D. M. Shim, S. W. Seo. Silencing of translation initiation factor eIF3b promotes apoptosis in osteosarcoma cells. 2017;6:186-193. DOI: 10.1302/2046-3758.63.BJR-2016-0151.R2.

摘要

目的

真核生物翻译起始因子3(eIF3)是一种多亚基复合物,在翻译起始过程中起关键作用。eIF3亚基的表达水平在各种癌症中升高或降低,提示eIF3在肿瘤发生中发挥作用。最近的研究表明,eIF3b亚基在膀胱癌和前列腺癌中表达升高,eIF3b沉默可抑制胶质母细胞瘤生长并诱导细胞凋亡。在本研究中,我们调查了eIF3b在骨肉瘤细胞存活中的作用。

方法

为了研究eIF3b对骨肉瘤细胞活力和凋亡的影响,我们首先检测了eIF3b在U2OS细胞中的沉默效果。分别通过细胞计数试剂盒-8(CCK-8)检测和蛋白质印迹法检测细胞活力和凋亡情况。我们还进行了基因谱分析,以鉴定受eIF3b沉默影响的基因。最后,在多个骨肉瘤细胞系中证实了eIF3b对细胞活力和凋亡的影响。

结果

eIF3b沉默降低了U2OS细胞的活力并诱导其凋亡,通过基因谱分析我们发现eIF3b沉默还导致肿瘤坏死因子受体超家族成员21(TNFRSF21)上调。我们发现TNFRSF21过表达诱导U2OS细胞死亡,并且我们证实eIF3b沉默完全抑制了多个骨肉瘤细胞系中的细胞生长。然而,eIF3b沉默未能完全抑制正常成纤维细胞中的细胞生长。

结论

我们的数据使我们得出结论,eIF3b可能通过调节TNFRSF21的表达来促进骨肉瘤细胞增殖。Y. J. Choi、Y. S. Lee、H. W. Lee、D. M. Shim、S. W. Seo。翻译起始因子eIF3b沉默促进骨肉瘤细胞凋亡。2017年;6:186 - 193。DOI:10.1302/2046 - 3758.63.BJR - 2016 - 0151.R2。

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