4.5 Article

Oncogenic role of phospholipase C-γ1 in progression of hepatocellular carcinoma

Journal

HEPATOLOGY RESEARCH
Volume 49, Issue 5, Pages 559-569

Publisher

WILEY
DOI: 10.1111/hepr.13309

Keywords

hepatocellular carcinoma; PLCG1; prognosis; tumor growth

Funding

  1. National Natural Science Foundation of China [81871920, 81702306, 81672334, 81772590]

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Aim Phospholipase C-gamma 1 (PLCG1) was previously found to be involved in a variety of oncogenic behaviors such as cell motility, cell proliferation, cell migration, and invasion. However, its function in hepatocellular carcinoma (HCC) was unknown. Here, we explored the expression pattern and function of PLCG1 in HCC progression. Methods Expression of PLCG1 was examined by western blotting in hepatoma cells and human tumor tissues. Expression was also detected by immunohistochemistry in 150 HCC clinical samples, and its clinical significance was analyzed. The influence of PLCG1 on HCC carcinogenesis were determined in vitro and in vivo. The underlying mechanisms were explored by detecting the expression of critical molecules of signaling pathways. Results The results showed that PLCG1 was overexpressed in hepatoma cell lines and clinical HCC tissues. Increased PLCG1 expression in tumor tissues was remarkably correlated with poor clinical features of HCC. Patients with positive PLCG1 expression in tumor tissues had shorter overall survival and relapse-free survival. Phospholipase C gamma 1 could substantially promote cell proliferation, anchor growth, and cell invasion in vitro. The in vivo study showed that inhibition of PLCG1 in hepatoma cells significantly repressed tumor growth in nude mice. Furthermore, we showed that PLCG1 might exert its function by activating the mitogen-activated protein kinase and nuclear factor-kappa B signaling pathways. Conclusion Our data indicated that PLCG1 could act as an oncogene in HCC carcinogenesis and could serve as a valuable prognostic marker and potential therapeutic target for HCC.

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