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Abstract
Dysregulated expression of long non-coding RNAs (lncRNAs) has been reported in many types of cancers, indicating that it has important regulatory roles in human cancer biology. Recently, lncRNA urothelial cancer-associated 1 (UCA1) was shown to be dysregulated in many cancer types, but the detailed mechanisms remain largely unknown. In our study, we found that upregulated UCA1 is associated with poor prognosis in gastric cancer patients. Further experiments revealed that UCA1 knockdown significantly repressed the proliferation and migration both in vitro and in vivo. Moreover, RNA sequencing (RNA-seq) analysis revealed that UCA1 knockdown preferentially affected genes that are linked to cell proliferation, cell cycle, and cell migration. Mechanistically, UCA1 promotes cell proliferation progression through repressing p21 and Sprouty RTK signaling antagonist 1 (SPRY1) expression by binding to EZH2. We found that UCA1 could mediate the trimethylation of H3K27 in promoters of p21 and SPRY1. To our knowledge, this is the first report showing the global gene profile of downstream targets of UCA1 in the progression of gastric cancer. Collectively, our data reveal the important roles of UCA1 in gastric cancer (GC) oncogenesis.
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1 Department of Anatomy, Histology and Embryology, The Research Center for Bone and Stem Cells, Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China
2 Department of Anatomy, Histology and Embryology, The Research Center for Bone and Stem Cells, Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China
3 The Fourth Clinical Medical College, Nanjing Medical Universtiy, Nanjing, Jiangsu, People’s Republic of China
4 Department of Oncology, Xuzhou Central Hospital, The Xuzhou School of Clinical Medicine of Nanjing Medical University, Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China
5 Department of Clinical Research Center, Nanjing Second Hospital, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, People’s Republic of China
6 Department of General Surgery, Pizhou City People’s Hospital, Pizhou City 221300, Jiangsu Province, China
7 Department of Epidemiology and Biostatistics, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China