Lim Yongchul, Yu Suyeun, Yun Jung-A, Do In-Gu, Cho Lan, Kim Yang Hee, Kim Hee Cheol
Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Department of Preventive Medicine, College of Medicine, Korea University, Seoul, Korea.
Oncotarget. 2017 Dec 27;9(10):9010-9020. doi: 10.18632/oncotarget.23809. eCollection 2018 Feb 6.
Protein arginine methylation is involved in cellular differentiation and proliferation. Recently, aberrant expression of protein arginine methyltransferases, which are responsible for the methylation reaction, has been reported in various types of cancer. However, there is no clear evidence regarding the prognostic value of abnormal PRMT6 expression in colorectal cancer or the effect of PRMT6 regulation on CRC cells. We investigated the expression patterns of PRMT6 in patients with stage II and III CRC. We detected nuclear expression of PRMT6 in 23.7% of carcinoma samples by immunohistochemistry. Among the clinicopathological parameters, the ratio of poorly differentiated cancer cells was approximately two-fold higher in patients with PRMT6-positive disease than in those with PRMT6-negative disease ( = 0.002). Patients with PRMT6-positive CRC had a shorter disease-free survival than those with PRMT6-negative CRC in both univariate and multivariate analyses ( = 0.018 and = 0.035, respectively). siRNA-mediated inhibition of PRMT6 expression in CRC cells induced p21 overexpression and suppressed cell growth and colony-forming ability. Concomitantly, apoptosis was induced in PRMT6-suppressed CRC cells. These data suggest that PRMT6 can serve as a biomarker for unfavorable prognosis and as a therapeutic target in CRC.
蛋白质精氨酸甲基化参与细胞分化和增殖。最近,负责甲基化反应的蛋白质精氨酸甲基转移酶的异常表达已在各种类型的癌症中被报道。然而,关于PRMT6异常表达在结直肠癌中的预后价值或PRMT6调控对结直肠癌细胞的影响,尚无明确证据。我们研究了II期和III期结直肠癌患者中PRMT6的表达模式。通过免疫组织化学,我们在23.7%的癌组织样本中检测到PRMT6的核表达。在临床病理参数中,PRMT6阳性疾病患者中低分化癌细胞的比例比PRMT6阴性疾病患者高约两倍(P = 0.002)。在单因素和多因素分析中,PRMT6阳性的结直肠癌患者的无病生存期均短于PRMT6阴性的患者(分别为P = 0.018和P = 0.035)。siRNA介导的对结直肠癌细胞中PRMT6表达的抑制诱导了p21的过表达,并抑制了细胞生长和集落形成能力。同时,在PRMT6抑制的结直肠癌细胞中诱导了凋亡。这些数据表明,PRMT6可作为结直肠癌不良预后的生物标志物和治疗靶点。