RIF1 promotes human epithelial ovarian cancer growth and progression via activating human telomerase reverse transcriptase expression
research target：RIF1、epithelial ovarian cancer
Periodicals：J Exp Clin Cancer Res
IF：6.217
Cooperative Unit：Department of Clinical Pharmacology, Xiangya Hospital, Central South University
Time of publication：August，2018
Summary
Background: Human telomerase reverse transcriptase (hTERT) is highly expressed in over 80% of tumors, includinghuman epithelial ovarian cancer (EOC). However, the mechanisms through which hTERT is up-regulated in EOC and promotes tumor progression remain unclear. The aim of this study is to identify RIF1 as a novel molecular targetthat modulate hTERT signaling and EOC growth.
Methods: RIF1 expression in ovarian cancer, benign and normal ovarian tissues was examined byimmunohistochemistry. The biological role of RIF1 was revealed by MTS, colony formation and sphere formationassays. Luciferase reporter assay and chromatin immunoprecipitation (CHIP) assay were used to verify RIF1 as anovel hTERT promoter-binding protein in EOC cells. The role of RIF1 on tumorigenesis in vivo was detected by thexenograft model.
Results: RIF1 expression is upregulated in EOC tissues and is closely correlated with FIGO stage and prognosis ofEOC patients. Functionally, RIF1 knockdown suppressed the expression and promoter activity of hTERT and consequently inhibited the growth and CSC-like traits of EOC cells. RIF1 knockdown also inhibited tumorigenesis inxenograft model. RIF1 overexpression had the opposite effect. Luciferase reporter assay and ChIP assay verified RIF1directly bound to hTERT promoter to upregulate its expression. The rescue experiments suggested hTERToverexpression rescued the inhibition of EOC cell growth and CSC-like traits mediated by RIF1 knockdown.Consistently, hTERT knockdown abrogated the RIF1-induced promotion of EOC cell growth and CSC-like traits.
Conclusions: RIF1 promotes EOC progression by activating hTERT and the RIF1/hTERT pathway may be a potentialtherapeutic target for EOC patients.
