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  • br Summary It is well accepted that


    Summary It is well-accepted that tumorigenesis including viral tumorigenesis including ten important hallmarks: evading growth suppressors, activating invasion & metastasis, genome instability & mutation, inducing angiogenesis, enabling replicative immortality, sustaining proliferative signaling, resisting cell death, reregulating cellular energetics, avoiding immune destruction, and tumor promoting inflammation [3]. As we discussed in previous sections, mitochondria were reported involved in at least seven of them in 5 common oncoviruses covered in this review (Fig. 1). Mitochondria are ubiquitous organelles in eukaryotic Spectinomycin whose primary role is to generate energy supplies in the form of ATP through oxidative phosphorylation. Recent studies have also shown that mitochondria play a central role in modulating cell growth, host immune response and apoptosis [105], [106], [107]. They are in essence the major cellular hub for bioenergetics, biosynthesis and signal transduction. Human viral oncogenesis often involves persistent infections and overcoming resistance by the host's immune reactions. Taking control of mitochondria and then integrating mitochondrial pathways are the central goals to achieve, first for viral survival and replication and ultimately for viral oncogenesis. We have discussed viral-mitochondrial interactions with 5 major oncoviruses as summarized in Fig. 2. Such interactions certainly go beyond these common viruses. With human T lymphotropic virus type 1 (HTLV-1), p13II protein targets the mitochondrial inner membrane where it produces a membrane potential-dependent influx of potassium, leading to mitochondrial swelling and fragmentation, and altered mitochondrial calcium uptake [108]. The C-terminal peptides of F1L protein from vaccinia virus (VACV or VV) bind to mitochondria and interfere with apoptosis by inhibiting the loss of MMP [109] and inhibiting apoptosis [110]. The vMIA protein of Cytomegalovirus (CMV) binds Bax to form a vMIA-Bax complex which blocks Bax-mediated mitochondrial membrane permeabilization [111]. The UL12.5 protein of Herpes simplex virus-1 (HSV-1) targets onto mitochondria to induce the rapid and complete degradation of host mitochondrial DNA [112].
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    Introduction Hepatocellular carcinoma (HCC) is actually the sixth cause of cancer-related death in the world and it is estimated to become the third cause in Western countries by 2030, despite the reducing incidence of chronic hepatitis infections [1]. The explanation for this unexpected increase of incidence may be found in the significant change in the field of liver cancer epidemiology. In fact, an increasing number of HCCs develop on liver metabolic disorders including Non Alcoholic Fatty Liver Disease (NAFLD) and Nonalcoholic Steatohepatitis (NASH), which are becoming the new precancerous conditions, in addition to the traditionally known virus-induced cirrhosis. Therefore, metabolic risk factors commonly associated to NAFLD or NASH, including diabetes mellitus type II, obesity and metabolic syndrome are becoming emerging risk factors for HCC. This is based upon epidemiological evidence showing the significant relationship of these conditions with incidence of HCC, regardless of the common risk factors such as chronic hepatitis or alcohol abuse. Therefore, it is not surprising the growing scientific interest during the last few years on the oncogenic mechanisms underlying the transition from liver metabolic disorders to HCC involving these new metabolic risk factors. This review focuses on the pathogenic role of the emerging factors involved in the transition from steatosis to HCC. These factors include insulin resistance, inflammation, lipid and bile acids metabolism and the gut microbiota. A better understanding of the impact of these factors on the liver microenvironment may have potential benefit on the management of liver disease.