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阿司匹林通过抑制 Blimp1 并激活 ATF4/CHOP 通路在多发性骨髓瘤中发挥抗肿瘤作用。

Aspirin exerts anti-tumor effect through inhibiting Blimp1 and activating ATF4/CHOP pathway in multiple myeloma.

机构信息

Department of Medical Laboratory, First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan, 450052, China.

Department of Medical Laboratory, The Second Affiliated Hospital of Henan University of Traditional Chinese Medicine 450052, China.

出版信息

Biomed Pharmacother. 2020 May;125:110005. doi: 10.1016/j.biopha.2020.110005. Epub 2020 Feb 25.

Abstract

B lymphocyte-induced maturation protein-1 (Blimp1) is a key regulator that promotes the terminal differentiation of mature B lymphocytes into plasma cells, and is essential for the survival of Multiple myeloma (MM)cells. However, the expression of Blimp1 in MM and its effect on the signaling pathway remain unknown. Studies have found that during long-term endoplasmic reticulum (ER) stress, activated ATF4 may also stimulate the CCAAT-enhancer-binding protein homologous protein (CHOP) gene, triggering the unfolded protein response (UPR) terminal apoptotic pathway in plasma cells. Moreover Aspirin can induce MM cell apoptosis through mitochondria and death receptor pathway. Therefore, we aim to explore whether Aspirin could induce AFT4/CHOP apoptosis pathway in MM by inhibiting Blimp1 expression, thereby promoting MM cell apoptosis and exerting anti-tumor effects.

摘要

B 淋巴细胞诱导成熟蛋白 1(Blimp1)是一种关键的调节因子,可促进成熟 B 淋巴细胞向浆细胞的终末分化,是多发性骨髓瘤(MM)细胞存活所必需的。然而,Blimp1 在 MM 中的表达及其对信号通路的影响尚不清楚。研究发现,在长期内质网(ER)应激下,激活的 ATF4 也可能刺激 CCAAT 增强子结合蛋白同源蛋白(CHOP)基因,触发浆细胞中未折叠蛋白反应(UPR)末端凋亡途径。此外,阿司匹林可以通过线粒体和死亡受体途径诱导 MM 细胞凋亡。因此,我们旨在探讨阿司匹林是否可以通过抑制 Blimp1 的表达,从而诱导 MM 细胞中 AFT4/CHOP 凋亡途径,促进 MM 细胞凋亡并发挥抗肿瘤作用。

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