RIF1 promotes human epithelial ovarian cancer growth and progression via activating human telomerase reverse transcriptase expression
Abstract 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...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2018-08-01
|
| Series: | Journal of Experimental & Clinical Cancer Research |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13046-018-0854-8 |
| _version_ | 1828898626089254912 |
|---|---|
| author | Yong-Bin Liu Ying Mei Jing Long Yu Zhang Dong-Li Hu Hong-Hao Zhou |
| author_facet | Yong-Bin Liu Ying Mei Jing Long Yu Zhang Dong-Li Hu Hong-Hao Zhou |
| author_sort | Yong-Bin Liu |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-12-13T15:18:40Z |
| format | Article |
| id | doaj.art-d6fa6ab33280410bb774cc7665f709dd |
| institution | Directory Open Access Journal |
| issn | 1756-9966 |
| language | English |
| last_indexed | 2024-12-13T15:18:40Z |
| publishDate | 2018-08-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Experimental & Clinical Cancer Research |
| spelling | doaj.art-d6fa6ab33280410bb774cc7665f709dd2022-12-21T23:40:38ZengBMCJournal of Experimental & Clinical Cancer Research1756-99662018-08-0137111510.1186/s13046-018-0854-8RIF1 promotes human epithelial ovarian cancer growth and progression via activating human telomerase reverse transcriptase expressionYong-Bin Liu0Ying Mei1Jing Long2Yu Zhang3Dong-Li Hu4Hong-Hao Zhou5Department of Clinical Pharmacology, Xiangya Hospital, Central South UniversityDepartment of Clinical Pharmacology, Xiangya Hospital, Central South UniversityDepartment of Obstetrics & Gynecology, Xiangya Hospital, Central South UniversityDepartment of Obstetrics & Gynecology, Xiangya Hospital, Central South UniversityDepartment of Clinical Pharmacology, Xiangya Hospital, Central South UniversityDepartment of Clinical Pharmacology, Xiangya Hospital, Central South UniversityAbstract 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.http://link.springer.com/article/10.1186/s13046-018-0854-8Ovarian cancerRIF1Telomerase reverse transcriptasehTERT |
| spellingShingle | Yong-Bin Liu Ying Mei Jing Long Yu Zhang Dong-Li Hu Hong-Hao Zhou RIF1 promotes human epithelial ovarian cancer growth and progression via activating human telomerase reverse transcriptase expression Journal of Experimental & Clinical Cancer Research Ovarian cancer RIF1 Telomerase reverse transcriptase hTERT |
| 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 | Ovarian cancer RIF1 Telomerase reverse transcriptase hTERT |
| url | http://link.springer.com/article/10.1186/s13046-018-0854-8 |
| work_keys_str_mv | AT yongbinliu rif1promoteshumanepithelialovariancancergrowthandprogressionviaactivatinghumantelomerasereversetranscriptaseexpression AT yingmei rif1promoteshumanepithelialovariancancergrowthandprogressionviaactivatinghumantelomerasereversetranscriptaseexpression AT jinglong rif1promoteshumanepithelialovariancancergrowthandprogressionviaactivatinghumantelomerasereversetranscriptaseexpression AT yuzhang rif1promoteshumanepithelialovariancancergrowthandprogressionviaactivatinghumantelomerasereversetranscriptaseexpression AT donglihu rif1promoteshumanepithelialovariancancergrowthandprogressionviaactivatinghumantelomerasereversetranscriptaseexpression AT honghaozhou rif1promoteshumanepithelialovariancancergrowthandprogressionviaactivatinghumantelomerasereversetranscriptaseexpression |