Nuclear PRMT1 expression is associated with poor prognosis and chemosensitivity in gastric cancer patients
Nuclear PRMT1 expression is associated with poor prognosis and chemosensitivity in gastric cancer patients
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DOI：
10.1007/s10120-015-0551-7
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发表时间：
2016-07-01
期刊：
影响因子：
7.4
通讯作者：
Kuwano, Hiroyuki
中科院分区：
文献类型：
--
作者：
Altan, Bolag;Yokobori, Takehiko;Kuwano, Hiroyuki
转移性和难治性胃癌（GC）与预后不良相关，因此，确定预后因素和化疗敏感性标志物是非常重要的。蛋白质精氨酸甲基转移酶1（PRMT 1）可能通过激活肿瘤抑制因子叉头盒O 1（FOXO 1）在化疗敏感性/凋亡诱导中发挥作用。本研究采用免疫组化方法检测195例胃癌组织中PRMT 1和FOXO 1的表达，探讨PRMT 1和FOXO 1在胃癌组织中的表达及其相互关系。我们使用小干扰RNA对PRMT 1进行抑制分析，以确定PRMT 1在化疗敏感性中的生物学作用。PRMT 1和FOXO 1在GC样品中主要表达于细胞核。PRMT 1表达较低的患者（n = 131）与PRMT 1表达较高的患者（n = 64）相比，FOXO 1的核积聚受到抑制，辅助化疗后复发率较高，预后较差。通过RNA干扰在GC细胞中下调PRMT 1可抑制顺铂和5-氟尿嘧啶的敏感性。PRMT 1小干扰RNA组中磷酸化FOXO 1和磷酸化BCL-2细胞死亡拮抗剂的表达上调。我们的数据表明，评估PRMT 1在胃癌中的表达是一个有用的预测预后不良和辅助化疗后复发的指标。此外，这些数据表明PRMT 1是克服难治性GC的有希望的治疗工具。
Metastatic and refractory gastric cancer (GC) are associated with a poor prognosis; therefore, the identification of prognostic factors and chemosensitivity markers is extremely important. Protein arginine methyltransferase 1 (PRMT1) may play a role in chemosensitivity/apoptosis induction via activation of the tumor suppressor forkhead box O1 (FOXO1). The purpose of this study was to clarify the expression of and relationship between PRMT1 and FOXO1 to evaluate the applicability of PRMT1 as a prognostic marker and a therapeutic tool in GC.We investigated the clinical and functional significance of PRMT1 and FOXO1 in 195 clinical GC samples using immunohistochemistry. We performed suppression analysis of PRMT1 using small interfering RNA to determine the biological roles of PRMT1 in chemosensitivity.PRMT1 and FOXO1 in GC samples were predominantly expressed in the nucleus. Patients with lower PRMT1 expression (n = 131) had suppressed nuclear accumulation of FOXO1, higher recurrence after adjuvant chemotherapy, and poorer prognosis than those with higher PRMT1 expression (n = 64). PRMT1 downregulation in GC cells by RNA interference inhibited cisplatin and 5-fluorouracil sensitivity. The expression of phosphorylated FOXO1 and phosphorylated BCL-2 antagonist of cell death was upregulated in PRMT1 small interfering RNA groups.Our data suggest that the evaluation of PRMT1 expression in GC is a useful predictor of poor prognosis and recurrence after adjuvant chemotherapy. Moreover, these data suggest that PRMT1 is a promising therapeutic tool for overcoming refractory GC.