Stress-Induced Premature Senescence Promotes Proliferation by Activating the and P16/Retinoblastoma (Rb) Pathway in Diffuse Large B-Cell Lymphoma

Overview

Journal Turk J Haematol

Specialty Hematology

Date 2019 Jul 23

PMID 31327185

Citations 3

Authors

Jiyu Wang

Zhitao Wang

Huiping Wang

Zhixiang Wanyan

Ying Pan

Fengfeng Zhu

Qianshan Tao

Zhimin Zhai

Affiliations

Soon will be listed here.

Abstract

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 ( gene-encoding protein), p16/p21, and Rb/pRb were measured with western blot. LY8 cells were transfected with -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 -SiRNA group compared with the negative control group.

Conclusion: SIPS formation activates ARHGAP18 and the p16/Rb pathway and promotes DLBCL cell proliferation. Furthermore, activates the p16 pathway in DLBCL. SIPS promotes proliferation by activating and the p16/Rb pathway in DLBCL. -related SIPS may serve as an important target for relapsed/refractory DLBCL therapy.

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