RNAi-mediated c-Rel silencing leads to apoptosis of B cell tumor cells and suppresses antigenic immune response in vivo.
RNAi-mediated c-Rel silencing leads to apoptosis of B cell tumor cells and suppresses antigenic immune response in vivo.
复制标题
RNAi介导的C-REL沉默导致B细胞肿瘤细胞的凋亡，并抑制体内抗原免疫反应。
DOI：
10.1371/journal.pone.0005028
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发表时间：
2009
期刊：
影响因子：
3.7
通讯作者：
Liou HC
中科院分区：
文献类型：
--
作者：
Tian W;Liou HC
c-Rel是Rel/NF-κB转录因子家族的成员，主要在淋巴细胞和髓细胞中表达，在淋巴细胞增殖和存活中起关键作用。c-Rel信号转导通路的持续激活与过敏、炎症、自身免疫性疾病和多种人类恶性肿瘤有关。为了探索靶向c-Rel作为治疗这些疾病的药物的潜力，我们设计了一种小干扰RNA （siRNA）来在体外和体内沉默c-Rel的表达。C-Rel-siRNA通过逆转录病毒载体在B细胞肿瘤细胞系中表达，导致肿瘤细胞生长停滞和凋亡。体外沉默原代B细胞中的c-Rel会损害其对CD40激活信号的增殖和存活反应，类似于c-Rel敲除B细胞的反应受损。最重要的是，体内c-Rel的沉默会导致T细胞介导的抗原刺激免疫反应的显著损伤。因此，我们的研究验证了c-Rel-siRNA的有效性，并建议开发基于sirna的治疗方法以及小分子抑制剂来治疗B细胞肿瘤和自身免疫性疾病。
c-Rel is a member of the Rel/NF-κB transcription factor family and is predominantly expressed in lymphoid and myeloid cells, playing a critical role in lymphocyte proliferation and survival. Persistent activation of the c-Rel signal transduction pathway is associated with allergies, inflammation, autoimmune diseases, and a variety of human malignancies. To explore the potential of targeting c-Rel as a therapeutic agent for these disorders, we designed a small interfering RNA (siRNA) to silence c-Rel expression in vitro and in vivo. C-Rel-siRNA expression via a retroviral vector in a B cell tumor cell line leads to growth arrest and apoptosis of the tumor cells. Silencing c-Rel in primary B cells in vitro compromises their proliferative and survival response to CD40 activation signals, similar to the impaired response of c-Rel knockout B cells. Most important, in vivo silencing of c-Rel results in significant impairment in T cell-mediated immune responses to antigenic stimulation. Our study thus validates the efficacy of c-Rel-siRNA, and suggests the development of siRNA-based therapy, as well as small molecular inhibitors for the treatment of B cell tumors as well as autoimmune diseases.
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影响因子：
4.4
作者：
Andjelic, S;Hsia, C;Liou, HC
通讯作者：
Liou, HC
DOI：
10.1084/jem.187.2.147
发表时间：
1998-01-19
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Franzoso G;Carlson L;Poljak L;Shores EW;Epstein S;Leonardi A;Grinberg A;Tran T;Scharton-Kersten T;Anver M;Love P;Brown K;Siebenlist U
通讯作者：
Siebenlist U
影响因子：
2.1
作者：
Chiorazzi, Nicholas
通讯作者：
Chiorazzi, Nicholas
影响因子：
8
作者：
Fan, YJ;Rayet, B;Gélinas, C
通讯作者：
Gélinas, C
DOI：
10.1038/nrd2310
发表时间：
2007-06
期刊：
Nature reviews. Drug discovery
影响因子：
--
作者：
de Fougerolles A;Vornlocher HP;Maraganore J;Lieberman J
通讯作者：
Lieberman J