UHRF1 promotes proliferation of gastric cancer via mediating tumor suppressor gene hypermethylation.
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.
['Zhou|Lin|L|', 'Shang|Yulong|Y|', "Jin|Zhi'an|Z|", 'Zhang|Wei|W|', 'Lv|Chunlei|C|', 'Zhao|Xiaodi|X|', 'Liu|Yongqiang|Y|', 'Li|Naiyi|N|', 'Liang|Jie|J|']
D000368:Aged D000818:Animals D022762:CCAAT-Enhancer-Binding Proteins D045744:Cell Line, Tumor D019175:DNA Methylation D044127:Epigenesis, Genetic D005260:Female D015972:Gene Expression Regulation, Neoplastic D016147:Genes, Tumor Suppressor D006801:Humans D053208:Kaplan-Meier Estimate D008297:Male D008807:Mice, Inbred BALB C D008819:Mice, Nude D008875:Middle Aged D011379:Prognosis D011401:Promoter Regions, Genetic D013274:Stomach Neoplasms D044767:Ubiquitin-Protein Ligases D023041:Xenograft Model Antitumor Assays
UHRF1 proliferation gastric cancer tumor suppressor gene BRCA, breast cancer CDH4, cadherin 4 CDKN2A, cyclin-dependent kinase inhibitor 2A CDX2, caudal type homeobox 2 DNA methylation DNMT, DNA methyltransferase FOXO, forkhead box O GAPDH, glyceraldehyde 3-phosphate dehydrogenase GC, gastric cancer GO, gene ontology MSP, methylation-specific PCR NC, negative control PBS, phosphate buffered saline PI, propidium iodide PLA, Chinese People's Liberation Army PML, promyelocytic leukemia PPARG,peroxisome proliferator-activated receptor gamma RB, retinoblastoma protein RUNX3, runt-related transcription factor 3 TSG, tumor suppressor gene UHRF1, ubiquitin-like containing PHD ring finger 1 mRNA, messenger RNA qRT-PCR, quantitative reverse transcription–polymerase chain reaction shRNA, short hairpin RNA