Nan-Hua Chou1, Yi-Hao Lo2, Kuo-Chiang Wang1, Chi-Hsiang Kang1, Chung-Yu Tsai1, Kuo-Wang Tsai3,4,5. 1. Division of General Surgery, Department of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, R.O.C. 2. Department of Family Medicine, Zuoying Branch of Kaohsiung Armed Forces General Hospital, Kaohsiung, Taiwan, R.O.C. 3. Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, R.O.C. kwtsai6733@gmail.com. 4. Department of Chemical Biology, National Pingtung University of Education, Pingtung, Taiwan, R.O.C. 5. Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan, R.O.C.
Abstract
BACKGROUND/AIM: MicroRNAs (miRNAs) are small non-protein-coding RNAs, that can be generated from the 5p or 3p arm of precursor miRNA (pre-miRNA). Differential miRNA arm selection has been reported between tumor and normal tissue in many cancer types; however, the biological function and mechanism of miRNA arm switching in gastric cancer remain unclear. MATERIALS AND METHODS: Profiles of miRNA expression in gastric cancer were obtained from The Cancer Genome Atlas (TCGA). The biological role of miR-193a-5p/-3p in tumor growth and invasive abilities was assessed through a gain-of-function approach. Target genes of miR-193a-3p were identified using bioinformatics and an experimental approach. RESULTS: The expression levels of miR-193a-5p, and not of miR-193a-3p, were significantly decreased in gastric cancer compared to adjacent normal tissues. Ectopic expressions of miR-193a-5p and miR-193a-3p revealed that they both inhibited gastric cancer cell growth, but only miR-193a-3p significantly suppressed cell invasion ability. Using a bioinformatics approach, we identified 18 putative target genes of miR-193a-3p. Both mRNA and protein levels of cyclin D1 (CCND1) and ETS proto-oncogene 1 (ETS1) were significantly decreased in AGS cells transfected with miR-193a-3p mimics. ETS1 or CCND1 knockdown significantly suppressed gastric cancer cell growth, similar to miR-193a-3p overexpression. CONCLUSION: Our results indicated that miR-193a-3p suppressed gastric growth and motility, at least partly, by directly targeting CCND1 and ETS1 expression. Copyright
BACKGROUND/AIM: MicroRNAs (miRNAs) are small non-protein-coding RNAs, that can be generated from the 5p or 3p arm of precursor miRNA (pre-miRNA). Differential miRNA arm selection has been reported between tumor and normal tissue in many cancer types; however, the biological function and mechanism of miRNA arm switching in gastric cancer remain unclear. MATERIALS AND METHODS: Profiles of miRNA expression in gastric cancer were obtained from The Cancer Genome Atlas (TCGA). The biological role of miR-193a-5p/-3p in tumor growth and invasive abilities was assessed through a gain-of-function approach. Target genes of miR-193a-3p were identified using bioinformatics and an experimental approach. RESULTS: The expression levels of miR-193a-5p, and not of miR-193a-3p, were significantly decreased in gastric cancer compared to adjacent normal tissues. Ectopic expressions of miR-193a-5p and miR-193a-3p revealed that they both inhibited gastric cancer cell growth, but only miR-193a-3p significantly suppressed cell invasion ability. Using a bioinformatics approach, we identified 18 putative target genes of miR-193a-3p. Both mRNA and protein levels of cyclin D1 (CCND1) and ETS proto-oncogene 1 (ETS1) were significantly decreased in AGS cells transfected with miR-193a-3p mimics. ETS1 or CCND1 knockdown significantly suppressed gastric cancer cell growth, similar to miR-193a-3p overexpression. CONCLUSION: Our results indicated that miR-193a-3p suppressed gastric growth and motility, at least partly, by directly targeting CCND1 and ETS1 expression. Copyright