Stress-Induced Premature Senescence Promotes Proliferation by Activating the SENEX and p16INK4a/Retinoblastoma (Rb) Pathway in Diffuse Large B-Cell Lymphoma
Stress-Induced Premature Senescence Promotes Proliferation by Activating the SENEX and p16INK4a/Retinoblastoma (Rb) Pathway in Diffuse Large B-Cell Lymphoma
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压力诱导的过早衰老通过激活弥漫性大 B 细胞淋巴瘤中的 SENEX 和 p16INK4a/视网膜母细胞瘤 (Rb) 通路促进增殖
DOI：
10.4274/tjh.galenos.2019.2019.0117
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发表时间：
2019-11
期刊：
影响因子：
--
通讯作者：
Zhimin Zhai
中科院分区：
文献类型：
--
作者：
Jiyu Wang;Zhitao Wang;Huiping Wang;Zhixiang Wanyan;Ying Pan;Fengfeng Zhu;Qianshan Tao;Zhimin Zhai
目的：细胞衰老被认为是肿瘤形成的重要屏障。最近的研究表明，应激诱导的早衰（SIPS）可以促进肿瘤的部分侵袭，但SIPS如何影响弥漫性大B细胞淋巴瘤（DLBCL）仍然没有定论。本研究旨在解决这一问题。材料与方法：流式细胞术检测LY 8细胞的免疫表型。衰老β-半乳糖苷酶染色检测过氧化叔丁基（tBHP）诱导的SIPS。用CCK 8分析细胞增殖，用Western blot测量ARHGAP 18（SENEX基因编码蛋白）、p16/p21和Rb/pRb的表达水平。用SENEX-SiRNA/NC转染LY 8细胞并通过蛋白质印迹验证。结果如下：结果提示，LY 8细胞系的免疫表型为CD 19-、CD 20-和CD 10-阳性，免疫球蛋白轻链为κ型。30 μM tBHP可成功诱导DLBCL细胞衰老模型。与其他组相比，SIPS组ARHGAP 18、p21、p16和Rb蛋白水平显著升高，而pRb表达水平降低。同时，SIPS组细胞增殖率高于其他tBHP组。此外，与阴性对照组相比，SENEX-SiRNA组p21和p16的表达显著降低。结论：SIPS的形成激活了ARHGAP 18和p16/Rb信号通路，促进DLBCL细胞增殖。此外，SENEX激活DLBCL中的p16通路。SIPS通过激活SENEX和p16/Rb通路促进DLBCL的增殖。SENEX相关SIPS可能作为复发/难治性DLBCL治疗的重要靶点。
Objective: Cellular senescence has been thought to be an important barrier to tumor formation. Recent studies have shown that stress-induced premature senescence (SIPS) can promote partial tumor invasion, but how SIPS affects diffuse large B-cell lymphoma (DLBCL) remains inconclusive. This study aimed to address that issue. Materials and Methods: The immunophenotype of the LY8 cell line was measured with flow cytometry. SIPS induced by tert-butyl hydroperoxide (tBHP) was detected by senescence β-galactosidase staining. Cell proliferation was analyzed with CCK8 and expression levels of ARHGAP18 (SENEX gene-encoding protein), p16/p21, and Rb/pRb were measured with western blot. LY8 cells were transfected with SENEX-SiRNA/NC and verified by western blot. Results: Our results suggested that the immunophenotype of the LY8 cell line is CD19-, CD20-, and CD10-positive and the immunoglobulin light chain is the kappa type. The cellular senescence model of DLBCL could be successfully induced by 30 μM tBHP. ARHGAP18, p21, p16, and Rb protein levels were significantly increased but the level of pRb expression was decreased in the SIPS group compared with other groups. Meanwhile, the proliferation rate was increased in the SIPS group more than other tBHP groups. Furthermore, the expressions of p21 and p16 were significantly decreased in the SENEX-SiRNA group compared with the negative control group. Conclusion: SIPS formation activates ARHGAP18 and the p16/Rb pathway and promotes DLBCL cell proliferation. Furthermore, SENEX activates the p16 pathway in DLBCL. SIPS promotes proliferation by activating SENEX and the p16/Rb pathway in DLBCL. SENEX-related SIPS may serve as an important target for relapsed/refractory DLBCL therapy.
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DOI：
10.1007/978-3-642-02202-9_346
发表时间：
2012
期刊：
--
影响因子：
--
作者：
H. S. Nicholson
通讯作者：
H. S. Nicholson
影响因子：
14.5
作者：
Yaswen P;MacKenzie KL;Keith WN;Hentosh P;Rodier F;Zhu J;Firestone GL;Matheu A;Carnero A;Bilsland A;Sundin T;Honoki K;Fujii H;Georgakilas AG;Amedei A;Amin A;Helferich B;Boosani CS;Guha G;Ciriolo MR;Chen S;Mohammed SI;Azmi AS;Bhakta D;Halicka D;Niccolai E;Aquilano K;Ashraf SS;Nowsheen S;Yang X
通讯作者：
Yang X
影响因子：
20.3
作者：
Coleman, Paul R.;Hahn, Christopher N.;Gamble, Jennifer R.
通讯作者：
Gamble, Jennifer R.
影响因子：
3.7
作者：
HAYFLICK, L;MOORHEAD, PS
通讯作者：
MOORHEAD, PS
影响因子：
21.3
作者：
Campaner, Stefano;Doni, Mirko;Amati, Bruno
通讯作者：
Amati, Bruno