Abstract
Background Inflammation is the major risk factor for the progression of hepatocellular carcinoma (HCC), and the nuclear factor-κB (NF-κB) signaling plays the central role in the inflammation process. However, the activated mechanism of NF-κB 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-κB signaling. In addition, blocking the NF-κB 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-κB signaling and knockdown of PHF5A downregulates the activity of NF-κB pathway to inhibit the tumor progression. The above results provide the evidence that PHF5A plays an indispensable role in progressive effect of NF-κB pathway in HCC and may be a novel therapeutic target of HCC.
Highlights
Liver cancer is evaluated to be the sixth most commonly diagnosed cancer and the fourth leading cause of cancer death worldwide in 2018, with about 841,000 new cases and 782,000 deaths annually [1]
The analysis demonstrated that the PHF5A expression is significantly upregulated in 365 primary hepatocellular carcinoma (HCC) tissues compared to 50 normal liver tissues (Figure 1(a), P < 0.0001)
Kaplan-Meier survival analysis demonstrated that the overall survival of HCC patients with high expression of PHF5A is significantly shorter than that of patients with low expression of PHF5A using the data from the Cancer Genome Atlas (TCGA) (Figure 1(d))
Summary
Liver cancer is evaluated to be the sixth most commonly diagnosed cancer and the fourth leading cause of cancer death worldwide in 2018, with about 841,000 new cases and 782,000 deaths annually [1]. Inflammation is the major risk factor for the progression of hepatocellular carcinoma (HCC), and the nuclear factor-κB (NF-κB) signaling plays the central role in the inflammation process. Downregulation of PHF5A inhibits the migration and invasion of HCC cells. Blocking the NF-κB signaling can weaken the stimulatory effect of PHF5A on migration and invasion of HCC cells. 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-κB signaling and knockdown of PHF5A downregulates the activity of NF-κB pathway to inhibit the tumor progression. The above results provide the evidence that PHF5A plays an indispensable role in progressive effect of NF-κB pathway in HCC and may be a novel therapeutic target of HCC
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