Role of microRNA-26b in the development of Hepatitis C Virus associated diffuse large B-cell lymphomas

• Applicant: Dr. Jan Peveling-Oberhag
• Subject Area: Gastroenterology ; Hematology, Oncology ; Cell Biology
• Term: from 2014 to 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 252646706

Chronic hepatitis C virus (HCV) infection is associated with an increased risk to develop malignant lymphoma. Complete remission of HCV associated lymphoma can be achieved using antiviral therapy only. The molecular pathogenesis of this viral cancer-induction remains elusive.MicroRNAs (miRNAs) function as important regulators of various cell functions; e.g. proliferation, apoptosis and cancerogenesis. In previous works the author could already show that miRNAs might be involved in the pathogenesis of HCV-induced lymphomagenesis. A decreased expression of miR-26b, a miRNA known to have tumor suppressive properties, was identified in splenic marginal zone lymphomas (SMZL) arising in HCV positive patients.Aims of this project are the expression analysis of miR-26b in various HCV-associated lymphomas as well as functional studies in vitro and in vivo to gain insight into the molecular pathogenesis of a potential miR-26b-mediated lymphomagenesis. The working plan includes the expression analysis of miR-26b in primary tumor tissue of different lymphoma subtypes in patients with- and without chronic HCV infection. Furthermore, with the use of lentiviral transduction, the effect of an increased expression of miR-26b on lymphoma cell lines will be investigated. Moreover, it is planned to study the interaction of HCV and miR-26b in lymphoma development using a mouse model with constitutive expression of the complete HCV genome in murine B-cells (RZCD19Cre mouse). The potential discovery of pathomechanisms in HCV associated lymphomagenesis may offer the opportunity to develop novel specific cancer therapies. Such tumor therapies are especially needed in the treatment of HCV associated lymphoma subtypes with high malignancy, such as diffuse large B-cell lymphoma. The planed studies, the establishing of the mentioned mouse model and numerous parallels with the pathogenesis of other tumor diseases with viral etiology offer the opportunity to initiate follow-up projects in the future.

• DFG Programme: Research Grants