Xu Meng, Jia Yuli, Liu Zhikui, Ding Linglong, Tian Run, Gu Hua, Wang Yufeng, Zhang Hongyong, Tu Kangsheng, Liu Qingguang
Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China.
Onco Targets Ther. 2016 Jul 1;9:4023-35. doi: 10.2147/OTT.S107050. eCollection 2016.
Several studies have revealed that the abnormal expression of chromatin assembly factor 1, subunit A (P150) (CHAF1A) was involved in the development of some types of malignant tumors. However, CHAF1A expression and its role in hepatocellular carcinoma (HCC) remain poorly characterized. In this study, we first investigated CHAF1A expression in six cell lines and 116 pairs of HCC and matched normal tumor-adjacent tissues to evaluate the clinicopathological characteristics of CHAF1A in HCC. Then, we detected the proliferation and apoptosis in HCC cells. In addition, a subcutaneous tumor model in nude mice was performed to evaluate tumor growth in vivo. We found that the expression of CHAF1A was significantly higher in HCC tissues than that in adjacent nontumor tissues (P<0.01). Clinical analysis indicated that CHAF1A expression was significantly correlated with the tumor-node-metastasis stage, tumor number, and tumor differentiation in HCC tissues (P<0.05, respectively). We also found that CHAF1A may potentially function as a poor prognostic indicator for 5-year overall and disease-free survival in patients with HCC (P<0.05, respectively). The elevated expression of CHAF1A was also observed in HCC cell lines compared with that in normal LO2 hepatic cell line (P<0.01). HCC cancer cells exhibited inhibition of cell growth, reduction in colony-formation ability, increased cell apoptosis rate, and impaired tumorigenicity in nude mice after CHAF1A knockdown. Collectively, we propose that CHAF1A by potentially mediating cancer cell proliferation plays an important role in promoting the development of HCC and may serve as a potential therapeutic target in HCC.
多项研究表明,染色质组装因子1亚基A(P150)(CHAF1A)的异常表达与某些类型恶性肿瘤的发生发展有关。然而,CHAF1A在肝细胞癌(HCC)中的表达及其作用仍不清楚。在本研究中,我们首先检测了CHAF1A在6种细胞系以及116对HCC组织和配对的癌旁正常组织中的表达,以评估CHAF1A在HCC中的临床病理特征。然后,我们检测了HCC细胞的增殖和凋亡情况。此外,还建立了裸鼠皮下肿瘤模型以评估体内肿瘤生长情况。我们发现,CHAF1A在HCC组织中的表达显著高于癌旁非肿瘤组织(P<0.01)。临床分析表明,CHAF1A表达与HCC组织的肿瘤-淋巴结-转移分期、肿瘤数量和肿瘤分化显著相关(分别为P<0.05)。我们还发现,CHAF1A可能是HCC患者5年总生存率和无病生存率的不良预后指标(分别为P<0.05)。与正常LO2肝细胞系相比,HCC细胞系中也观察到CHAF1A表达升高(P<0.01)。CHAF1A基因敲低后,HCC癌细胞表现出细胞生长抑制、集落形成能力降低、细胞凋亡率增加以及裸鼠致瘤性受损。综上所述,我们认为CHAF1A可能通过介导癌细胞增殖在促进HCC发展中起重要作用,并可能成为HCC的潜在治疗靶点。