Downregulation of PHF6 Inhibits Cell Proliferation and Migration in Hepatocellular Carcinoma

Downregulation of PHF6 Inhibits Cell Proliferation and Migration in Hepatocellular Carcinoma
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DOI:
10.1089/cbr.2018.2671
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发表时间:
2019-05-01
影响因子:
3.4
通讯作者:
Zhou, Jianyin
Zhou, Jianyin
中科院分区:
医学4区
文献类型:
--
作者:
Yu, Qiangfeng;Yin, Libo;Zhou, Jianyin

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背景资料:植物同源结构域指6(PHF 6)最初被鉴定为Borjeson-Forssman-Lehmann综合征中的单基因突变,据报道其是T细胞急性淋巴细胞白血病的肿瘤抑制因子。然而,PHF 6在肝细胞癌(HCC)中的生物学功能一直很差。材料与方法:在本研究中,我们首先采用实时荧光定量PCR技术检测了肝癌组织和癌旁正常组织中PHF 6的mRNA水平。用siRNA转染肝癌细胞株HepG 2、SMMC-7721和Bel-7402,使PHF 6的表达下调。在HCC细胞中进行了一系列功能实验,包括EdU增殖测定、集落形成测定和Transwell测定。Western blot检测PHF 6、E-cadherin和Vimentin的表达。结果如下:我们发现PHF 6在HCC组织中显著升高,并与TNM分期、分化程度和淋巴结转移呈正相关。沉默PHF 6显著抑制HCC细胞的增殖、集落形成和迁移。此外,沉默PHF 6明显增加E-cadherin的表达,降低Vimentin的表达。结论:这些结果表明,PHF 6在肝癌细胞的生长中起着积极的作用,靶向PHF 6可以作为一个有前途的治疗策略,为人类肝癌。
Background: The plant homeodomain finger 6 (PHF6) was originally identified as single gene mutated in Borjeson-Forssman-Lehmann syndrome, which was reported to be a tumor suppressor in T-cell acute lymphoblastic leukemia. However, the biological function of PHF6 in hepatocellular carcinoma (HCC) has been poorly characterized. Materials and Methods: In this study, we first determined the mRNA levels of PHF6 in HCC tissues and adjacent normal tissues using quantitative real-time PCR. Then the expression of PHF6 was knocked down in HCC cell lines (HepG2, SMMC-7721, and Bel-7402) by siRNA transfection. A series of functional experiments, including EdU proliferation assay, colony formation assay, and Transwell assay, were performed in HCC cells. Western blot analysis was used to detect the expression of PHF6, E-cadherin, and Vimentin. Results: We found that PHF6 was significantly elevated in HCC tissues and positively correlated with TNM stage, differentiation, and lymph node metastasis. Silencing PHF6 significantly inhibited cell proliferation, colony formation, and migration in HCC cells. Furthermore, silencing PHF6 obviously increased E-cadherin and decreased Vimentin expression. Conclusions: These findings suggest that PHF6 plays a positive role in the growth of HCC cells, and targeting PHF6 could serve as a promising therapeutic strategy for human HCC.