USP21 promotes cell proliferation by maintaining the EZH2 level in diffuse large B-cell lymphoma.

USP21 promotes cell proliferation by maintaining the EZH2 level in diffuse large B-cell lymphoma.
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USP21通过维持弥漫性大B细胞淋巴瘤的EZH2水平促进细胞增殖。

DOI:
10.1002/jcla.23693
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发表时间:
2021-03
影响因子:
2.7
通讯作者:
Xie W
Xie W
中科院分区:
医学4区
文献类型:
--
作者:
Ma H;Luo X;Zhou P;He N;Zhou J;Liu M;Xie W

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弥漫性大B细胞淋巴瘤(DLBCL)是最常见的非霍奇金淋巴瘤(NHL)。然而,DLBCL的潜在分子机制仍不清楚。进行真实的-时间PCR和蛋白质印迹分析以评估泛素特异性肽酶21(USP 21)或zeste 2多梳抑制复合物2亚基增强子(EZH 2)的表达。分别采用CCK 8法和细胞死亡染色法检测USP 21在细胞增殖和细胞死亡中的作用。我们发现去泛素化酶USP 21在DLBCL淋巴组织中高度表达。USP 21的表达促进DLBCL细胞增殖,但对细胞死亡无明显影响。此外,我们发现USP 21通过半胱氨酸221(USP 21的催化位点)调节细胞增殖。此外,我们发现USP 21可以稳定EZH 2,这是一种生发中心形成和淋巴瘤形成所需的蛋白质。去泛素化酶USP 21通过维持DLBCL中的EZH 2蛋白水平来促进细胞增殖。USP 21在弥漫性大B-细胞淋巴瘤(DLBCL)中富集,有利于肿瘤细胞增殖。从机制上讲,USP 21通过维持EZH 2蛋白水平促进细胞生长。我们的数据表明USP 21可以作为DLBCL的有希望的治疗靶点。
Diffuse large B‐cell lymphoma (DLBCL) is the most common category of non‐Hodgkin lymphoma (NHL). However, the underlying molecular mechanism of DLBCL remains unclear. Real‐time PCR and Western blot analysis were performed to assess the expression of ubiquitin‐specific peptidase 21 (USP21) or enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2). CCK8 assay and cell death staining were carried out to examine the role of USP21 in cell proliferation and cell death, respectively. We found that the deubiquitinase USP21 was highly expressed in the DLBCL lymphoid tissue. The expression of USP21 promoted DLBCL cell proliferation, while it had no obvious effect on cell death. In addition, we found that USP21 regulated cell proliferation via cysteine 221, the catalytic site of USP21. Furthermore, we identified that USP21 could stabilize EZH2, a protein required for germinal center formation and lymphoma formation. The deubiquitinase USP21 promotes cell proliferation by maintaining the EZH2 protein level in DLBCL. USP21 is enriched in diffuse large B‐cell lymphoma (DLBCL) and is beneficial for tumor cell proliferation. Mechanistically, USP21 promotes cell growth by maintaining EZH2 protein level. Our data suggest that USP21 can act as a promising therapeutic target for DLBCL.
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