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Introduction
Hepatocellular carcinoma (HCC), one of the most prevalent human cancers, is the third leading cause of cancer-related deaths worldwide. Although there are diverse treatments for HCC, such as surgical resection, radiofrequency ablation, radiotherapy and chemoembolization, the prognosis of patients with HCC remains poor (1–3). Thus, it is necessary to develop a deeper understanding of the molecular mechanisms to identify new molecular markers that can be used for early diagnosis and therapy of HCC, and to improve the outcome of these patients. Recent studies have focused on the important role of the tumor microenvironment in the progression, invasion and metastasis of HCC (4–6). Tumor-associated macrophages (TAMs) are the most abundant cellular component of the tumor microenvironment, and they play essential roles in the treatment of cancers, such as pancreatic cancer and HCC (7,8). Previous studies have shown that TAMs are primarily characterized as alternatively activated M2-like macrophages, with high expression levels of peroxisome proliferator-activated receptor (PPAR), CD206 and arginase (Arg)-1, and low expression levels of tumor necrosis factor-α (TNF-α). In addition, M2-like TAMs play leading roles in immune suppression by interacting with stromal cells, which greatly contributes to HCC growth, invasion and metastasis (9–11). These studies suggest that targeting the regulation of TAM polarization presents a potential therapeutic strategy for HCC.
Receptor-interacting protein 140 (RIP140) is a nuclear receptor co-regulator that affects biological and pathological processes in the body, including energy metabolism, inflammatory response and tumorigenesis (12–14). Previous studies have found that RIP140-mediated macrophage polarization plays an essential role in regulating the inflammatory response. Overexpression of RIP140 in macrophages promoted macrophages to an M1-like polarization and expanded the inflammatory response. Conversely, lowering the level of RIP140 in macrophages not only reduced M1-like macrophages, but also expanded alternative polarization and promoted endotoxin tolerance (ET), which relieves the inflammatory response (13,15,16). However, the role of RIP140 in TAMs remains completely unknown.
In the present study, we demonstrated that RIP140 expression in TAMs plays a role in the growth of hepatoma cells, which is closely related to the prognosis of patients with liver cancer. Our data, presented in the present study, identified RIP140 as a potential target in HCC immunotherapy that may promote macrophage-mediated antitumor immunity.
Materials and methods
Cell lines and cell cultures
Human HCC cell lines...