Viral hepatitis with hepatitis C virus or hepatitis B virus and chronic liver disease such as alcoholic or nonalcoholic steatohepatitis are critical factors in the development of hepatocellular carcinoma (HCC). Furthermore, diabetes is known as an independent risk factor for HCC. Peroxisome proliferator-activated receptor (PPAR) is known to have an important role in fatty liver, and the mechanism of carcinogenesis has been clarified. PPAR controls ligand-dependent transcription, and three subtypes (α, δ, and γ) in humans are known. PPARs could contribute to the mechanisms of cell cycling, anti-inflammatory responses, and apoptosis. Therefore, to clarify the pathogenesis of HCC, we should examine PPAR signaling. In this paper, we have summarized the relevance of PPARs to the pathogenesis of HCC and cancer stem cells and possible therapeutic options through modifying PPAR signaling. 1. Introduction Worldwide, the mortality from hepatocellular carcinoma represents one-third of all cancer deaths with more than 1 million a year [1]. In the early stages of hepatocellular carcinoma, when patients maintain a hepatic functional reserve, local treatment such as hepatic resection or radio-frequency ablation is relatively effective [2]. However, many patients die from repeated recurrence. Hepatic arterial infusion chemotherapy (HAIC) [3, 4] for advanced hepatocellular carcinoma is only sometimes effective. Also, sorafenib (VEGF-2/PDGFR-beta inhibitor) [5], which has come in to use recently, has not shown satisfactory results [6, 7]. Therefore, finding a new therapeutic target molecule has become very important. Viral hepatitis with HCV or HBV and chronic liver disease such as alcohol or nonalcoholic steatohepatitis (NASH) [8] are critical factors in the development of hepatocellular carcinoma. Furthermore, diabetes is known as an independent risk factor for hepatocellular carcinoma [9, 10]. In addition, the hepatitis C is known to become fatty liver at a high rate [11, 12]. Peroxisome proliferator-activated receptor (PPAR) [13, 14] plays an important role in fatty liver, and its involvement in carcinogenesis has been clarified. PPAR controls ligand-dependent transcription, and three subtypes (α, δ, and γ) in humans are known. PPARα [14] is present in liver, kidney, heart, and small intestine and has an important role in the regulation of lipid metabolism [15]. PPARγ is expressed in adipose tissue and macrophages. It is involved in adipose cell differentiation and lipid uptake and has anti-inflammatory effects. In addition, PPARγ expression is induced in the liver
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