RYBP blocking peptide

The expression of Ring1and YY1 binding protein (RYBP) is reduced in several human cancers, but the molecular mechanism( s) have remained elusive. In this study, we used human hepatocellular carcinoma (HCC) cell lines and tissue specimens to study the mechanism and herein report several new findings. First, we cloned and characterized the basal promoter region of the human RYBP gene. We found that the decreased RYBP expression in HCC tissues was not due to promoter sequence variation/polymorphisms orCpGdinucleotide methylation. Weidentified two transcription factors, KLF4 and Sp1, which directly bind the promoter region of RYBP to induce and suppress RYBP transcription, respectively. We mapped the binding sites of KLF4 and Sp1 on theRYBPpromoter. Studies in vitro showed that KLF4 suppresses whereas Sp1 promotesHCCcell growth through modulating RYBP expression. Deregulated KLF4 and Sp1 contributed to decreasedexpressionofRYBPinHCCtumortissues. Ourstudiesof human HCC tissues indicated that a diminished RYBP level in the tumor (in association with altered KLF4 and Sp1 expression) was statistically associated with a larger tumor size, poorer differentiation, and an increased susceptibility to distant metastasis. These findings help to clarifywhyRYBPis decreased inHCCand indicate that deregulated KLF4, Sp1, and RYBP may lead to a poorer prognosis. Our findings support the idea that RYBP may represent a target for cancer therapy and suggest that it may be useful as a prognostic biomarker for HCC, either alone or in combination with KLF4 and Sp1.