Song Aiqin, Ye Junli, Zhang Kunpeng, Yu Hongsheng, Gao Yanhua, Wang Hongfang, Sun Lirong, Xing Xiaoming, Yang Kun, Zhao Min
Department of Pediatric Hematology, Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, China.
Department of Pathophysiology, Medical College of Qingdao University, Qingdao, Shangdong 266021, China.
Leuk Res. 2015 May;39(5):536-43. doi: 10.1016/j.leukres.2015.02.007. Epub 2015 Feb 25.
Checkpoint with FHA and Ring Finger (CHFR) is a checkpoint protein that reportedly initiates a cell cycle delay in response to microtubule stress during prophase in mitosis, which has become an interesting target for understanding cancer pathogenesis. Recently, aberrant methylation of the CHFR gene associated with gene silencing has been reported in several cancers. In the present study, we examined the expression of CHFR in B-cell non-Hodgkin lymphoma (B-NHL) in vitro and in vivo. Our results showed that the expression level of CHFR mRNA and protein was reduced in B-NHL tissue samples and B cell lines. Furthermore, CHFR methylation was detected in 39 of 122 B-NHL patients, which was not found in noncancerous reactive hyperplasia of lymph node (RH) tissues. CHFR methylation correlated with the reduced expression of CHFR, high International Prognostic Index (IPI) scores and later pathologic Ann Arbor stages of B-NHL. Treatment with demethylation reagent, 5-Aza-dC, could eliminate the hypermethylation of CHFR, enhance CHFR expression and cell apoptosis and inhibit the cell proliferation of Raji cells, which could be induced by high expression of CHFR in Raji cells. Our results indicated that aberrant methylation of CHFR may be associated with the pathogenesis, progression for B-NHL, which might be a novel molecular marker as prognosis and treatment for B-NHL.
含FHA和环指结构域的细胞周期检查点蛋白（CHFR）是一种检查点蛋白，据报道，在有丝分裂前期，它可响应微管应激引发细胞周期延迟，这使其成为理解癌症发病机制的一个有趣靶点。最近，在几种癌症中均报道了与基因沉默相关的CHFR基因异常甲基化。在本研究中，我们检测了CHFR在B细胞非霍奇金淋巴瘤（B-NHL）体内外的表达情况。我们的结果显示，CHFR mRNA和蛋白的表达水平在B-NHL组织样本和B细胞系中降低。此外，在122例B-NHL患者中的39例检测到CHFR甲基化，而在非癌性淋巴结反应性增生（RH）组织中未发现。CHFR甲基化与CHFR表达降低、高国际预后指数（IPI）评分以及B-NHL较晚的病理Ann Arbor分期相关。用去甲基化试剂5-氮杂-2'-脱氧胞苷（5-Aza-dC）处理可消除CHFR的高甲基化，增强CHFR表达和细胞凋亡，并抑制Raji细胞的增殖，Raji细胞中CHFR的高表达可诱导上述变化。我们的结果表明，CHFR异常甲基化可能与B-NHL的发病机制及进展相关，这可能是一种用于B-NHL预后和治疗的新型分子标志物。
