Chromatin assembly factor 1, subunit A (P150) facilitates cell proliferation in human hepatocellular carcinoma.

Chromatin assembly factor 1, subunit A (P150) facilitates cell proliferation in human hepatocellular carcinoma.
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染色质组装因子 1,亚基 A (P150) 促进人肝细胞癌的细胞增殖。

DOI:
10.2147/ott.s107050
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发表时间:
2016
影响因子:
4
通讯作者:
Liu Q
Liu Q
中科院分区:
医学3区
文献类型:
--
作者:
Xu M;Jia Y;Liu Z;Ding L;Tian R;Gu H;Wang Y;Zhang H;Tu K;Liu Q

文献摘要

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多项研究表明,染色质组装因子1亚基A (P150) (CHAF1A)的异常表达参与了某些类型恶性肿瘤的发生发展。然而,CHAF1A的表达及其在肝细胞癌(HCC)中的作用仍然知之甚少。在本研究中,我们首先研究了CHAF1A在6个细胞系和116对HCC以及匹配的正常肿瘤邻近组织中的表达,以评估CHAF1A在HCC中的临床病理特征。然后,我们检测了肝癌细胞的增殖和凋亡。此外,我们还建立了裸鼠皮下肿瘤模型来评估肿瘤在体内的生长情况。我们发现CHAF1A在HCC组织中的表达明显高于癌旁非肿瘤组织(P<0.01)。临床分析显示CHAF1A表达与HCC组织中肿瘤-淋巴结-转移分期、肿瘤数量、肿瘤分化有显著相关性(P<0.05)。我们还发现CHAF1A可能作为HCC患者5年总生存率和无病生存率的不良预后指标(P<0.05)。CHAF1A在HCC细胞系中的表达也明显高于正常LO2肝细胞系(P<0.01)。CHAF1A基因敲除后,裸鼠肝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、致瘤性受损等特点。综上所述,我们认为CHAF1A通过潜在地介导癌细胞增殖,在促进HCC的发展中发挥了重要作用,并可能作为HCC的潜在治疗靶点。
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.