DL of C. procera has the potential for anti-cancer therapy due to its differentiable targets and non-interference with regular pathway of apoptosis.

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The pleiotropic HBx protein of hepatitis B virus is linked functionally to the development of hepatocellular carcinoma (HCC) via effectors and signalling pathways of the host. To identify such effectors in a macrocarcinogenic environment, a PCR-based cDNA subtraction analysis was carried out in the X15-myc oncomouse model of HCC. Altogether, 19 categories of genes, mainly involved in protein biosynthesis and the electron-transport chain, were found to be upregulated in the liver of these mice. Ribosomal protein S27a (RPS27a), which is a natural fusion protein of N-terminal ubiquitin and C-terminal extension protein (CEP), topped the list of expressed genes, with .20-fold higher expression compared with its normal level. Sustained and elevated expression of RPS27a in the mouse liver and its moderate expression in cell culture in the presence of HBx suggested an indirect role of RPS27a in hepatocarcinogenesis. Nevertheless, a remarkable change in the intracellular distribution of ubiquitin from cytoplasm to late-endosomal lysosomes, and of CEP from nucleoli to the perinucleolar region/nuclear foci, was observed in the presence of HBx. RPS27a accelerated the progression of the cell cycle and cooperated with HBx in this process. Further, the knockdown of RPS27a expression by RNA interference in an HBx microenvironment led to retarded cell-cycle progression and reduced cell size. Thus, these results suggest strongly that RPS27a could be an effector of HBx-mediated hepatocarcinogenesis. INTRODUCTIONChronic infection by hepatitis B virus (HBV) is a major public-health threat worldwide because of its reported association with cirrhosis, and more ominously hepatocellular carcinoma (HCC) (McMahon, 2009;Yang & Roberts, 2010). The oncogenic mechanisms of HBV have now begun to be elucidated. Multiple direct and indirect processes are involved in establishing HBV-related HCC (Kremsdorf et al., 2006). Integration of the HBV genome may stimulate tumorigenesis through either the cisactivation of cellular genes, such as the myc family of genes in woodchucks (Fourel et al., 1990), or transactivation by the viral X protein or HBx (Caselmann, 1996). HBx has been studied extensively for its role in HCC. It is a pleiotropic trans-activator that can stimulate a wide range of viral and cellular promoters (reviewed by Benhenda et al., 2009;Kumar & Sarkar, 2004). The oncogenic potential of HBx is evident from its ability to modulate tumorigenic signalling pathways (reviewed by Benhenda et al., 2009;Bouchard & Schneider, 2004), upregulate the expression of cellular oncogenes such as c-myc and c-jun (Caselmann, 1996) and functionally inactivate the tumour-suppressor protein p53 (Ueda et al., 1995). Besides, HBx can transform immortalized cells in vitro (Höhne et al., 1990; Shirakata et al., 1989) and induce liver-specific tumours in transgenic mouse models (reviewed by Kumar, 2008). There is constitutive activation of selected signalling pathways that promote cell growth and survival (Chemin & Zoulim, 2009).Although HBx stimulates a number...

Hepatocellular carcinoma (HCC) is the third leading malignancy worldwide, causing mortality in children and adults. AEG-1 is functioned as a scaffold protein for the proper assembly of RNA-induced silencing complex (RISC) to optimize or increase its activity. The increased activity of oncogenic miRNAs leads to the degradation of target tumor suppressor genes. miR-221 is an oncogenic miRNA, that plays a seminal role in carcinogenesis regulation of HCC. However, the molecular mechanism and biological functions of the miR-221/AEG-1 axis have not been investigated extensively in HCC. Here, the expression of miR-221/AEG-1 and their target/associate genes was analyzed by qRT-PCR and Western blot. The role of the miR-221/AEG-1 axis in HCC was evaluated by proliferation assay, migration assay, invasion assay, and flow cytometry analysis. The expression level of miR-221 decreased in AEG-1 siRNA transfected HCC cells. On the other hand, there were no significant expression changes of AEG-1 in miR-221 mimic and miR-221 inhibitor transfected HCC cells and inhibition of miR-221/AEG-1 axis decreased cell proliferation, invasion, migration, and angiogenesis and induced apoptosis, cell cycle arrest by upregulating p57, p53, PTEN, and RB and downregulating LSF, MMP9, OPN, Bcl-2, PI3K, AKT, and LC3A in HCC cells. Furthermore, these findings suggest that the miR-221/AEG-1 axis plays a seminal oncogenic role by modulating PTEN/PI3K/AKT signaling pathway in HCC. In conclusion, the miR-221/AEG-1 axis may serve as a potential target for therapeutics, diagnostics, and prognostics of HCC.