Potential role of High mobility group box 1 in hepatocellular carcinoma

Abstract

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide and is characterized as a typical inflammation-related carcinoma. High mobility group box protein 1 (HMGB1), a non-histone DNA-binding protein, is identified as a potent proinflammatory mediator when presents extracellularly. Recently, a growing body of evidence indicates that HMGB1 plays a potential role in HCC, but many questions remain unanswered about the relationship between HMGB1 and HCC formation and development. This review focuses on the biological effect of HMGB1, and discusses the association of HMGB1 with HCC and potential use of strategies targeting HMGB1 in HCC treatment.

Serum HMGB1 concentrations at 4 weeks is a useful predictor of extreme poor prognosis for advanced hepatocellular carcinoma treated with sorafenib and hepatic arterial infusion chemotherapy

“…A higher level of serum HMGB1 was reported to be correlated with larger tumor size, worse tumor stage, and pathological differentiation grades in these patients [32,38]. However, there has been no report investigating the usefulness of serum HMGB1 as a biomarker for advanced HCC patients who received treatment with sorafenib.…”

“…A recent study reported that HMGB1 translocates to the cytoplasm and is then actively secreted by HCC cells; extracellular HMGB1 can then promote cancer invasion and metastasis through TLR-4 signaling [19]. Recent studies have also suggested that targeting HMGB1 production or release might be potential approaches for HCC treatment [19,32,33].…”

“…Cytoplasmic HMGB1 was found to bind to a number of molecules related to cancer progression via promoting cell cycle progression, cell proliferation, and antiapoptosis [29,30]. Extracellular HMGB1 binds to several receptors, including the receptor for advanced glycation end products (RAGE), Toll-like receptor (TLR)-2, TLR-4, TLR-9, activating Ras-MAP kinase (MAPK) and the NF-jB/ MAPK pathway [31,32]. A recent study reported that HMGB1 translocates to the cytoplasm and is then actively secreted by HCC cells; extracellular HMGB1 can then promote cancer invasion and metastasis through TLR-4 signaling [19].…”

Heterogeneity of liver cancer and personalized therapy

“…HMGB1, secreted from hepatocytes in the process of liver inflammation such as NAFLD [47], also has been proven to promote HCC development [48]. Tsung et al demonstrated that HMGB1 could accelerate HCC progression through miR-21-mediated matrix metalloproteinase activity [49].…”

<p>microRNA-548b suppresses aggressive phenotypes of hepatocellular carcinoma by directly targeting high-mobility group box 1 mRNA</p>

“…The 3′-UTR of HMGB1 mRNA contains a complementary site for miR-548b ( Figure 4A), and this gene was chosen for validation because it has been implicated in hepatocarcinogenesis and cancer progression. [19][20][21][22][23][24][25][26][27][28][29][30][31] To test whether miR-548b can directly target the 3′-UTR of HMGB1 mRNA, wild-type and mutant luciferase plasmids were chemically synthesized and cotransfected with miR-548b mimics or the miR-548b inhibitor into Hep3B and SK-HEP-1 cells. MiR-548b overexpression in Hep3B cells decreased, whereas the miR-548b knockdown in SK-HEP-1 cells increased the luciferase activity of the plasmid harboring a wild-type miR-548b-binding site (P<0.05).…”