SIRT1-mediated downregulation of p27Kip1 is essential for overcoming contact inhibition of Kaposi's sarcoma-associated herpesvirus transformed cells.

ABSTRACT: Kaposi's sarcoma-associated herpesvirus (KSHV) is an oncogenic virus associated with Kaposi's sarcoma (KS), a malignancy commonly found in AIDS patients. Despite intensive studies in the last two decades, the mechanism of KSHV-induced cellular transformation and tumorigenesis remains unclear. In this study, we found that the expression of SIRT1, a metabolic sensor, was upregulated in a variety of KSHV-infected cells. In a model of KSHV-induced cellular transformation, SIRT1 knockdown with shRNAs or knockout by CRISPR/Cas9 gene editing dramatically suppressed cell proliferation and colony formation in soft agar of KSHV-transformed cells by inducing cell cycle arrest and contact inhibition. SIRT1 knockdown or knockout induced the expression of cyclin-dependent kinase inhibitor 1B (p27Kip1).

SUBMITTER: He M 

PROVIDER: S-EPMC5342771 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature