Drug Design, Development and Therapy (Oct 2021)
Translational Regulation in Hepatocellular Carcinogenesis
Abstract
Suzana Bracic Tomazic,1,2,* Christoph Schatz,3,* Johannes Haybaeck3,4 1Department of Pathology, Hospital Graz II, Graz, 8020, Austria; 2Faculty of Medicine, University of Maribor, Maribor, 2000, Slovenia; 3Institute of Pathology, Neuropathology and Molecular Pathology, Medical University of Innsbruck, Innsbruck, 6020, Austria; 4Diagnostic & Research Center for Molecular BioMedicine, Institute of Pathology, Medical University Graz, Graz, 8010, Austria*These authors contributed equally to this workCorrespondence: Johannes HaybaeckInstitute of Pathology, Neuropathology and Molecular Pathology, Medical University of Innsbruck, Müllerstraße 44, Innsbruck, 6020, AustriaTel +43 512 9003 71300Fax +43 512 9003 73301Email [email protected]: The mortality of hepatocellular carcinoma (HCC) is distributed unevenly worldwide. One of the major causes is hepatitis B or hepatitis C virus infection and the development and progression of liver cirrhosis. The carcinogenesis of HCC is among others regulated via the mTOR (mechanistic target of rapamycin) signaling pathway and represents a possible method of targeted treatment. The aim of our article was to address the most recent clinical advances and findings of basic studies on the mTOR signaling pathway and the involved factors. Risk factors play a key role in dysregulation of the signaling pathway, where both mTORCs are upregulated and protein synthesis is altered. eIFs and, to a lesser extent, eEFs play an essential role in this process. Whether the factor will be upregulated or downregulated, among others, depends on hepatitis B/C virus infection. The amount of a particular factor in a patient sample lets us know whether HCC recurrence will occur, what is the likelihood of chemoresistance, and what outcome is predicted for patients with an increased value. Our analysis shows that in addition to mTOR, eIF3, eIF4, and eIF5 play an important role, as they can serve as biomarkers for non- and virus-related HCC.Keywords: mTOR, virus related HCC, non-virus related HCC, cancer, translation initiation, liver
