UHRF1 promotes proliferation of gastric cancer via mediating tumor suppressor gene hypermethylation
| Autor: | Chun-Lei Lv, Xiaodi Zhao, Zhi'an Jin, Naiyi Li, Wei Zhang, Lin Zhou, Jie Liang, Yong-Qiang Liu, Yulong Shang |
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| Rok vydání: | 2015 |
| Předmět: |
Male
Cancer Research Tumor suppressor gene Ubiquitin-Protein Ligases Mice Nude Kaplan-Meier Estimate Biology medicine.disease_cause Epigenesis Genetic Downregulation and upregulation Stomach Neoplasms CDKN2A Cell Line Tumor medicine Animals Humans Gene silencing Genes Tumor Suppressor Epigenetics Promoter Regions Genetic Aged Pharmacology Mice Inbred BALB C Cancer DNA Methylation Middle Aged Prognosis medicine.disease Xenograft Model Antitumor Assays Gene Expression Regulation Neoplastic Oncology DNA methylation CCAAT-Enhancer-Binding Proteins Cancer research Molecular Medicine Female Carcinogenesis Research Paper |
| Zdroj: | Cancer Biology & Therapy. 16:1241-1251 |
| ISSN: | 1555-8576 1538-4047 |
| DOI: | 10.1080/15384047.2015.1056411 |
| Popis: | Epigenetic changes play significant roles in cancer development. UHRF1, an epigenetic regulator, has been shown to be overexpressed and to coordinate tumor suppressor gene (TSG) silencing in several cancers. In a previous study, we found that UHRF1 promoted gastric cancer (GC) invasion and metastasis. However, the role and underlying mechanism of UHRF1 in GC carcinogenesis remain largely unknown. In the present study, we investigated UHRF1 expression and function in GC proliferation and explored its downstream regulatory mechanism. The results demonstrated that UHRF1 overexpression was an independent and significant predictor of GC prognosis. Downregulation of UHRF1 suppressed GC proliferation and growth in vitro and in vivo, and UHRF1 upregulation showed opposite effects. Furthermore, downregulation of UHRF1 reactivated 7 TSGs, including CDX2, CDKN2A, RUNX3, FOXO4, PPARG, BRCA1 and PML, via promoter demethylation. These results provide insight into the GC proliferation process, and suggest that targeting UHRF1 represents a new therapeutic approach to block GC development. |
| Databáze: | OpenAIRE |
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