Regulation of mPGES-1 composition and cell growth via the MAPK signaling pathway in jurkat cells
Regulation of mPGES-1 composition and cell growth via the MAPK signaling pathway in jurkat cells
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DOI：
10.3892/etm.2018.6538
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发表时间：
2018-10-01
影响因子：
2.7
通讯作者：
Ma, Li-Ping
中科院分区：
文献类型：
--
作者：
Li, Yi-Qing;Chen, Jiao-Ting;Ma, Li-Ping
以往的研究表明，微粒体前列腺素E合成酶-1(mPGES-1)在多种类型的恶性肿瘤细胞中高表达，并与丝裂原活化蛋白激酶(MAPK)信号通路密切相关。然而，它们在T细胞急性淋巴细胞白血病(T-ALL)中的表达模式和功能在很大程度上仍不清楚。本研究探讨mPGES-1是否在T-ALL中起关键作用，并确定mPGES-1与T-ALL中MAPK信号通路之间的相互作用。结果表明，RNA沉默可显著降低T-ALL Jurkat细胞mPGES-1的过表达。持续下调mPGES-1可能抑制T-ALL JURKAT细胞的增殖，诱导细胞凋亡，并使细胞周期停滞。基因芯片和免疫印迹分析表明，c-jun氨基末端激酶在mPGES-1/前列腺素E2/EP4/MAPK正反馈环中起作用。此外，P38和细胞外信号调节激酶1/2对mPGES-1具有负反馈作用。综上所述，这些结果表明mPGES-1和MAPK信号通路之间的串扰是非常复杂的。因此，mPGES-1和MAPK信号通路的联合调控可能成为未来治疗T-ALL的一种新的候选方法。
Previous studies have suggested that microsomal prostaglandin E synthase-1 (mPGES-1) is highly expressed and closely associated with mitogen-activated protein kinase (MAPK) signaling pathways in various types of malignant cells. However, their expression patterns and function with respect to T-cell acute lymphoblastic leukemia (T-ALL) remain largely unknown. The present study investigated whether mPGES-1 served a crucial role in T-ALL and aimed to identify interactions between mPGES-1 and the MAPK signaling pathway in T-ALL. The results indicated that mPGES-1 overexpression in T-ALL jurkat cells was significantly decreased by RNA silencing. Decreasing mPGES-1 on a consistent basis may inhibit cell proliferation, induce apoptosis and arrest the cell cycle in T-ALL jurkat cells. Microarray and western blot analyses revealed that c-Jun N-terminal kinase served a role in the mPGES-1/prostaglandin E2/EP4/MAPK positive feedback loops. In addition, P38 and extracellular signal-regulated kinase 1/2 exhibited negative feedback effects on mPGES-1. In conclusion, the results suggested that cross-talk between mPGES-1 and the MAPK signaling pathway was very complex. Therefore, the combined regulation of mPGES-1 and the MAPK signaling pathway may be developed into a new candidate therapy for T-ALL in the future.