Stress-Induced Premature Senescence Promotes Proliferation by Activating the SENEX and p16INK4a/Retinoblastoma (Rb) Pathway in Diffuse Large B-Cell Lymphoma

被引:8
作者
Wang, Jiyu [1 ]
Wang, Zhitao [1 ]
Wang, Huiping [1 ]
Wanyan, Zhixiang [1 ]
Pan, Ying [1 ]
Zhu, Fengfeng [1 ]
Tao, Qianshan [1 ]
Zhai, Zhimin [1 ]
机构
[1] Anhui Med Univ, Dept Hematol, Affiliated Hosp 2, Hefei, Anhui, Peoples R China
基金
中国国家自然科学基金;
关键词
Stress-induced premature senescence; Proliferation; SENEX; p16; Rb/pRb; Diffuse large B-cell lymphoma; APOPTOSIS; PHENOTYPE; CANCER; GENE;
D O I
10.4274/tjh.galenos.2019.2019.0117
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 13-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 pM 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.
引用
收藏
页码:247 / 254
页数:8
相关论文
共 28 条
  • [1] Senescence versus apoptosis in chemotherapy
    Ansieau, Stephane
    Collin, Guillaume
    [J]. ONCOTARGET, 2015, 6 (07) : 4551 - 4552
  • [2] Non-Hodgkin lymphoma
    Armitage, James O.
    Gascoyne, Randy D.
    Lunning, Matthew A.
    Cavalli, Franco
    [J]. LANCET, 2017, 390 (10091) : 298 - 310
  • [3] Biomolecular bases of the senescence process and cancer. A new approach to oncological treatment linked to ageing
    Badiola, Iker
    Santaolalla, Francisco
    Garcia-Gallastegui, Patricia
    Ana, Sanchez-del Rey
    Unda, Fernando
    Ibarretxe, Gaskon
    [J]. AGEING RESEARCH REVIEWS, 2015, 23 : 125 - 138
  • [4] Novel immunotherapies in lymphoid malignancies
    Batlevi, Connie Lee
    Matsuki, Eri
    Brentjens, Renier J.
    Younes, Anas
    [J]. NATURE REVIEWS CLINICAL ONCOLOGY, 2016, 13 (01) : 25 - 40
  • [5] Cdk2 suppresses cellular senescence induced by the c-myc oncogene
    Campaner, Stefano
    Doni, Mirko
    Hydbring, Per
    Verrecchia, Alessandro
    Bianchi, Lucia
    Sardella, Domenico
    Schleker, Thomas
    Perna, Daniele
    Tronnersjo, Susanna
    Murga, Matilde
    Fernandez-Capetillo, Oscar
    Barbacid, Mariano
    Larsson, Lars-Gunnar
    Amati, Bruno
    [J]. NATURE CELL BIOLOGY, 2010, 12 (01) : 54 - U132
  • [6] Aging, Cellular Senescence, and Cancer
    Campisi, Judith
    [J]. ANNUAL REVIEW OF PHYSIOLOGY, VOL 75, 2013, 75 : 685 - 705
  • [7] Stressing the cell cycle in senescence and aging
    Chandler, Hollie
    Peters, Gordon
    [J]. CURRENT OPINION IN CELL BIOLOGY, 2013, 25 (06) : 765 - 771
  • [8] A Novel Cellular Senescence Gene, SENEX, Is Involved in Peripheral Regulatory T Cells Accumulation in Aged Urinary Bladder Cancer
    Chen, Tianping
    Wang, Huiping
    Zhang, Zhiqiang
    Li, Qing
    Yan, Kaili
    Tao, Qianshan
    Ye, Qianling
    Xiong, Shudao
    Wang, Yiping
    Zhai, Zhimin
    [J]. PLOS ONE, 2014, 9 (02):
  • [9] Stress-induced premature senescence mediated by a novel gene, SENEX, results in an anti-inflammatory phenotype in endothelial cells
    Coleman, Paul R.
    Hahn, Christopher N.
    Grimshaw, Matthew
    Lu, Ying
    Li, Xiaochun
    Brautigan, Peter J.
    Beck, Konstanze
    Stocker, Roland
    Vadas, Mathew A.
    Gamble, Jennifer R.
    [J]. BLOOD, 2010, 116 (19) : 4016 - 4024
  • [10] Biology of Cancer and Aging: A Complex Association With Cellular Senescence
    Falandry, Claire
    Bonnefoy, Marc
    Freyer, Gilles
    Gilson, Eric
    [J]. JOURNAL OF CLINICAL ONCOLOGY, 2014, 32 (24) : 2604 - +