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MicroRNA-429 Modulates Hepatocellular Carcinoma Prognosis and Tumorigenesis

DOI: 10.1155/2013/804128

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Abstract:

MicroRNA-429 (miR-429) may modify the development and progression of cancers; however, the role of this microRNA in the hepatocellular carcinoma (HCC) has not been well elaborated. Here, we tested miR-429 expression in 138 pathology-diagnosed HCC cases and SMMC-7721 cells. We found that miR-429 was upregulated in HCC tumor tissues and that the high expression of miR-429 was significantly correlated with larger tumor size (odd ratio (OR), 2.70; 95% confidence interval (CI), 1.28–5.56) and higher aflatoxin B1-DNA adducts (OR = 3.13, 95% CI = 1.47–6.67). Furthermore, this microRNA overexpression modified the recurrence-free survival and overall survival of HCC patients. Functionally, miR-429 overexpression progressed tumor cells proliferation and inhibited cell apoptosis. These results indicate for the first time that miR-429 may modify HCC prognosis and tumorigenesis and may be a potential tumor therapeutic target. 1. Introduction Primary liver cancer is the sixth most commonly occurring cancer worldwide, with an estimated 600,000 new cases per year [1–3]. Because of the very poor prognosis and the same number of deaths, this tumor is the third most common cause of cancer deaths in the world [2, 3]. Liver cancer is histopathologically classified into two major types, hepatocellular carcinoma (HCC) and cholangiocellular carcinoma. HCC often exhibits blood metastasis and recurrence [4–6]. Therefore, improvement in the therapy of recurrent or metastatic HCC now depends on improving our understanding of the complex molecular mechanisms governing the progression and aggressiveness of the disease. Over the last several decades, it has been recognized that multiple risks, including hepatitis B virus (HBV) and hepatitis C virus (HCV) infection, chemical carcinogen aflatoxin B1 (AFB1), and genetic abnormalities, are implicated in the multistep process of liver carcinogenesis [5–7]. Increasing evidence has shown that microRNA may play an important role in the tumorigenesis of this malignant [8–12], while microRNA-429 (miR-429), a member of the microRNA-200 family of microRNAs, can hinder the expression of transcriptional repressors SIP1/ZEB213 and ZEB1/deltaEF1 and regulate epithelial-mesenchymal transition [13, 14]. Recent studies have shown that downregulation of miR-429 may be an important late step in tumour progression [14]. Increasing data exhibit that dysregulation of this microRNA expression can modify tumor prognosis possibly through regulating cell proliferation and apoptosis [13, 15–18]. However, association between this microRNA and HCC has not yet been

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