RIF1 promotes human epithelial ovarian cancer growth and progression via activating human telomerase reverse transcriptase expression

Abstract

In this study, we show that RIF1 expression is upregulated in EOC tissues and is closely correlated with clinical stage and prognosis of EOC patients. [...]we have discovered and identified that RIF1 has a novel molecular feature in binding at the promoter of hTERT in EOC cell lines by chromatin immunoprecipitation assay and luciferase reporter assay. Since we have found RIF1 could regulate stemness related gene expression in Fig. 3f, to further confirm whether or not this regulation is dependent on hTERT, we explored whether hTERT knockdown could rescue the effect of RIF1 overexpression. RIF1 has Rap1 binding motif only in the budding yeast and localizes to native (capped) telomeres only in yeasts [42]. [...]the effect of RIF1 on telomere length regulation in yeasts is not conserved in mammalian cells and particularly in human cancer cells. Analysis of clinical samples in this study demonstrated that RIF1 expression was frequently up-regulated in EOC tissues and EOC cell lines compared with normal ovarian tissues and normal ovarian epithelial cell line and its overexpression associated with FIGO Stage (P < 0.001), overall survival (P = 0.0012) and progression-free survival (P < 0.001) of ovarian cancer patients. [...]the expression of RIF1 is positively correlated with hTERT expression in ovarian cancer tissues in two separate gene expression profiles from TCGA database and our own EOC tissue samples.