Role of hcv core protein in expression of the human telomerase reverse transcriptase (HTERT)‎ gene in hepatoma cell lines

Abstract EN

Hepatitis C virus is an oncogenic virus although the mechanisms responsible for this behavior are not clear.

Malignant transformation from mortal, normal cells to immortal, cancer cells is usually associated with activation of telomerase and subsequent telomere maintenance.

A major mechanism to regulate telomerase activity in human cells is transcriptional control of the human telomerase reverse transcriptase (h TERT) gene.

The aim of this study was to investigate the effects of HCV core protein on the regulation of Telomerase expression in human hepatoma cell lines.

Transient transfection and luciferase assay were used to evaluate h TERT promoter activity in cells cotransfected with Luciferase reporter plasmids carrying different regions of h TERT promoter and expression plasmids of HCV core proteins.

Reverse transcription-polymerase chain reaction (RT-PCR) and Immunofluorescence staining were used to analyze the expression of HCV core proteins.

H TERT promoter activity was increased about 4 folds in HCV core protein expressing cells (p CMV-Core) compared to vector-only controls.

By indirect immunofluorescence analysis, the core which was translated as a full-length protein of 191 amino acids (aa) was located in the cytoplasm.

While the cores designed to be truncated as a polypeptide of 173 aa and 151 aa were detected more in the nucleus.

Reporter assays with mutant fragments of the h TERT promoter further revealed that the h TERT promoter fragment (-86--46) contains an element that mediates HCV core protein-dependent expression of h TERT and its activation by HCV core protein is independent on Sp1.

It's concluded that hepatitis C virus core protein activation of h TERT promoter independent on Sp1 may contribute to HCV induced malignant transformation.