敲低 PHF5A 通过下调 NF-B 信号抑制 HCC 细胞的迁移和侵袭。
Knockdown of PHF5A Inhibits Migration and Invasion of HCC Cells via Downregulating NF-B Signaling.
机构信息
Department of Hepatic Surgery and Liver transplantation Center of the Third Affiliated Hospital, Organ Transplantation Institute, Sun Yat-sen University and Organ Transplantation Research Center of Guangdong Province, Guangzhou 510630, China.
Department of General Surgery, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510530, China.
出版信息
Biomed Res Int. 2019 Jan 15;2019:1621854. doi: 10.1155/2019/1621854. eCollection 2019.
BACKGROUND
Inflammation is the major risk factor for the progression of hepatocellular carcinoma (HCC), and the nuclear factor-B (NF-B) signaling plays the central role in the inflammation process. However, the activated mechanism of NF-B signaling in HCC is unclear.
METHODS
The expression of PHF5A is examined by qPCR, western blotting, and immunohistochemistry (IHC) assay. The potential of PHF5A (PHD-finger domain protein 5a) for migration and invasion is examined by wound healing and Transwell assay. Luciferase reporter assay, western blotting, and qPCR were applied to explore the mechanism by which PHF5A is involved in progression of HCC.
RESULTS
PHF5A was significantly upregulated in HCC tissues and cells. Downregulation of PHF5A inhibits the migration and invasion of HCC cells. Further study demonstrated that PHF5A is implicated in HCC progression through NF-B signaling. In addition, blocking the NF-B signaling can weaken the stimulatory effect of PHF5A on migration and invasion of HCC cells.
CONCLUSION
PHF5A expression is upregulated in HCC tissues, and depletion of PHF5A inhibits the migration and invasion of HCC cells. Further experiments demonstrated that PHF5A is implicated in NF-B signaling and knockdown of PHF5A downregulates the activity of NF-B pathway to inhibit the tumor progression. The above results provide the evidence that PHF5A plays an indispensable role in progressive effect of NF-B pathway in HCC and may be a novel therapeutic target of HCC.
背景
炎症是肝细胞癌（HCC）进展的主要危险因素，核因子-B（NF-B）信号在炎症过程中起着核心作用。然而，NF-B 信号在 HCC 中的激活机制尚不清楚。
方法
通过 qPCR、western blot 和免疫组织化学（IHC）检测 PHF5A 的表达。通过划痕愈合和 Transwell 检测 PHF5A（PHD 指状结构域蛋白 5a）的迁移和侵袭潜力。应用荧光素酶报告基因检测、western blot 和 qPCR 来探讨 PHF5A 参与 HCC 进展的机制。
结果
PHF5A 在 HCC 组织和细胞中明显上调。下调 PHF5A 抑制 HCC 细胞的迁移和侵袭。进一步的研究表明，PHF5A 通过 NF-B 信号参与 HCC 的进展。此外，阻断 NF-B 信号可以减弱 PHF5A 对 HCC 细胞迁移和侵袭的刺激作用。
结论
PHF5A 在 HCC 组织中表达上调，敲低 PHF5A 抑制 HCC 细胞的迁移和侵袭。进一步的实验表明，PHF5A 参与 NF-B 信号通路，敲低 PHF5A 下调 NF-B 通路的活性，抑制肿瘤进展。上述结果表明 PHF5A 在 HCC 中 NF-B 通路的渐进性效应中起着不可或缺的作用，可能成为 HCC 的新治疗靶点。
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