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RIF1 promotes human epithelial ovarian cancer growth and progression via activating human telomerase reverse transcriptase expression
BACKGROUND: Human telomerase reverse transcriptase (hTERT) is highly expressed in over 80% of tumors, including human 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 identif...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6091081/ https://www.ncbi.nlm.nih.gov/pubmed/30075819 http://dx.doi.org/10.1186/s13046-018-0854-8 |
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author | Liu, Yong-Bin Mei, Ying Long, Jing Zhang, Yu Hu, Dong-Li Zhou, Hong-Hao |
author_facet | Liu, Yong-Bin Mei, Ying Long, Jing Zhang, Yu Hu, Dong-Li Zhou, Hong-Hao |
author_sort | Liu, Yong-Bin |
collection | PubMed |
description | BACKGROUND: Human telomerase reverse transcriptase (hTERT) is highly expressed in over 80% of tumors, including human 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 target that modulate hTERT signaling and EOC growth. METHODS: RIF1 expression in ovarian cancer, benign and normal ovarian tissues was examined by immunohistochemistry. The biological role of RIF1 was revealed by MTS, colony formation and sphere formation assays. Luciferase reporter assay and chromatin immunoprecipitation (CHIP) assay were used to verify RIF1 as a novel hTERT promoter-binding protein in EOC cells. The role of RIF1 on tumorigenesis in vivo was detected by the xenograft model. RESULTS: RIF1 expression is upregulated in EOC tissues and is closely correlated with FIGO stage and prognosis of EOC 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 in xenograft model. RIF1 overexpression had the opposite effect. Luciferase reporter assay and ChIP assay verified RIF1 directly bound to hTERT promoter to upregulate its expression. The rescue experiments suggested hTERT overexpression 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 potential therapeutic target for EOC patients. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13046-018-0854-8) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-6091081 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-60910812018-08-20 RIF1 promotes human epithelial ovarian cancer growth and progression via activating human telomerase reverse transcriptase expression Liu, Yong-Bin Mei, Ying Long, Jing Zhang, Yu Hu, Dong-Li Zhou, Hong-Hao J Exp Clin Cancer Res Research BACKGROUND: Human telomerase reverse transcriptase (hTERT) is highly expressed in over 80% of tumors, including human 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 target that modulate hTERT signaling and EOC growth. METHODS: RIF1 expression in ovarian cancer, benign and normal ovarian tissues was examined by immunohistochemistry. The biological role of RIF1 was revealed by MTS, colony formation and sphere formation assays. Luciferase reporter assay and chromatin immunoprecipitation (CHIP) assay were used to verify RIF1 as a novel hTERT promoter-binding protein in EOC cells. The role of RIF1 on tumorigenesis in vivo was detected by the xenograft model. RESULTS: RIF1 expression is upregulated in EOC tissues and is closely correlated with FIGO stage and prognosis of EOC 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 in xenograft model. RIF1 overexpression had the opposite effect. Luciferase reporter assay and ChIP assay verified RIF1 directly bound to hTERT promoter to upregulate its expression. The rescue experiments suggested hTERT overexpression 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 potential therapeutic target for EOC patients. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13046-018-0854-8) contains supplementary material, which is available to authorized users. BioMed Central 2018-08-03 /pmc/articles/PMC6091081/ /pubmed/30075819 http://dx.doi.org/10.1186/s13046-018-0854-8 Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Liu, Yong-Bin Mei, Ying Long, Jing Zhang, Yu Hu, Dong-Li Zhou, Hong-Hao RIF1 promotes human epithelial ovarian cancer growth and progression via activating human telomerase reverse transcriptase expression |
title | RIF1 promotes human epithelial ovarian cancer growth and progression via activating human telomerase reverse transcriptase expression |
title_full | RIF1 promotes human epithelial ovarian cancer growth and progression via activating human telomerase reverse transcriptase expression |
title_fullStr | RIF1 promotes human epithelial ovarian cancer growth and progression via activating human telomerase reverse transcriptase expression |
title_full_unstemmed | RIF1 promotes human epithelial ovarian cancer growth and progression via activating human telomerase reverse transcriptase expression |
title_short | RIF1 promotes human epithelial ovarian cancer growth and progression via activating human telomerase reverse transcriptase expression |
title_sort | rif1 promotes human epithelial ovarian cancer growth and progression via activating human telomerase reverse transcriptase expression |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6091081/ https://www.ncbi.nlm.nih.gov/pubmed/30075819 http://dx.doi.org/10.1186/s13046-018-0854-8 |
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