Abstract
Hepatitis B virus (HBV) X protein (HBx) is implicated in the development of hepatocellular carcinoma (HCC). Yes-associated protein 1 (YAP) is an important proto-oncogene, which is a downstream effector molecule in the Hippo signaling pathway. The aim of the present study was to investigate the association between HBx expression in HCC samples and YAP expression in the Hippo pathway. A total of 20 pathologically confirmed HCC samples, 20 corresponding adjacent non-tumor liver tissues and 5 normal liver tissue samples were collected. The expression of HBx and YAP in the tissues was analyzed by quantitative reverse transcription-polymerase chain reaction and western blot analysis. The intensity and location of YAP expression were analyzed by immunohistochemistry. YAP mRNA and protein expression levels in HCC samples infected with HBV were significantly higher than those of normal liver tissues. Furthermore, YAP expression was positively correlated with HBx expression in HBV-positive HCC samples. Immunohistochemical staining revealed that YAP was predominantly expressed in the nuclei in HBV-positive HCC tissues. YAP expression was significantly decreased in the normal liver tissue and corresponding adjacent liver tissue when compared with the HCC tissues and by contrast to HCC tissues, YAP was predominantly located in the cytoplasm. In conclusion, these results indicate that the YAP gene is a key driver of HBx-induced liver cancer. Therefore, YAP may present a novel target in the treatment of HBV-associated HCC.
Highlights
Hepatocellular carcinoma (HCC) is the fifth most common type of cancer worldwide, and the incidence of hepatitis B virus (HBV)-related primary HCC isKey words: hepatitis B virus, X protein, Hippo signaling pathway55 cases/100,000 individuals for each gender [1]
The results revealed that Yes-associated protein 1 (YAP) mRNA levels in HBV‐associated HCC tissues were significantly higher than that of non‐tumor liver tissues (P
HBV X protein (HBx) exhibits an important function in HBV‐induced hepatocellular carcinoma [18]
Summary
Hepatocellular carcinoma (HCC) is the fifth most common type of cancer worldwide, and the incidence of hepatitis B virus (HBV)-related primary HCC is55 cases/100,000 individuals for each gender [1]. Yes-associated protein 1 (YAP) is a transcription factor in the Hippo signaling pathway [5], which regulates a number of transcription factors, including erb-b2 receptor tyrosine kinase 4, runt related transcription factor 2, p73, and TEA domain transcription factor 1 [6,7,8,9]. Transgenic mice overexpressing YAP exhibited an increased liver size and eventually developed liver cancer [11]. Clinical studies in HCC have demonstrated that YAP is an independent predictive factor of poor prognosis and overall survival [16]. In four HBV encoded proteins, HBV X protein (HBx) acts as a multifunctional regulatory protein, which exhibits an important function in HBV‐induced HCC [18]. It is hypothesized that HBx may be closely associated with YAP upregulation
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