Chaoyong Liu1, Minghua Ai1, Yan Zhang1, Jie Li1, Chao Xu2. 1. Department of Gastroenterology, First Affiliated Hospital of Yangtze University, No. 8, Hangkong Road, Shashi District, Jingzhou City, 434000, Hubei, China. 2. Department of Gastroenterology, First Affiliated Hospital of Yangtze University, No. 8, Hangkong Road, Shashi District, Jingzhou City, 434000, Hubei, China. xuchao_xucc@163.com.
Abstract
BACKGROUND: LncRNA ubiquitin-like with PHD and RING finger domains 1 (UHRF1) protein associated transcript (UPAT) regulates the progression of many cancers. However, its role in gastric cancer (GC) is less frequently reported. OBJECTIVE: In the context of the promoting effect of lncRNA on modulating GC progression, detailed insights into the role and underlying mechanism of UPAT in GC are the foothold in this study. METHODS: Overall survival was calculated. The mRNA expressions of UPAT and UHRF1 were measured by qRT-PCR, and the protein expressions of UHRF1, Cyclin D1 and cleaved caspase-3 were determined by western blot. Cell viability, growth, migration and invasion were assessed by CCK-8, colony formation, wound healing and Transwell assays, respectively. Apoptosis rate and cell cycle were assayed by flow cytometry. RESULTS: UPAT was overexpressed in GC tissue and cell lines. Decreased UPAT level was associated with higher overall survival. Down-regulation of UPAT diminished cell proliferation, Cyclin D1 expression, and migration and invasion rates, increased apoptosis rate and cleaved caspase-3 expression, and blocked cell cycle in AGS and NCI-N87 cells. UPAT expression in GC was positively correlated with UHRF1 expression. UHRF1 overexpression offset the inhibitory effects of UPAT down-regulation on cell proliferation, migration, invasion and cell cycle, and partially reversed the positive effect of UPAT down-regulation on apoptosis. CONCLUSION: UPAT might positively regulate the progression of GC via interacting with UHRF1. The UHRF1/UPAT axis revealed in the present study may provide a promising approach to intervene in the progression of GC.
BACKGROUND: LncRNA ubiquitin-like with PHD and RING finger domains 1 (UHRF1) protein associated transcript (UPAT) regulates the progression of many cancers. However, its role in gastric cancer (GC) is less frequently reported. OBJECTIVE: In the context of the promoting effect of lncRNA on modulating GC progression, detailed insights into the role and underlying mechanism of UPAT in GC are the foothold in this study. METHODS: Overall survival was calculated. The mRNA expressions of UPAT and UHRF1 were measured by qRT-PCR, and the protein expressions of UHRF1, Cyclin D1 and cleaved caspase-3 were determined by western blot. Cell viability, growth, migration and invasion were assessed by CCK-8, colony formation, wound healing and Transwell assays, respectively. Apoptosis rate and cell cycle were assayed by flow cytometry. RESULTS: UPAT was overexpressed in GC tissue and cell lines. Decreased UPAT level was associated with higher overall survival. Down-regulation of UPAT diminished cell proliferation, Cyclin D1 expression, and migration and invasion rates, increased apoptosis rate and cleaved caspase-3 expression, and blocked cell cycle in AGS and NCI-N87 cells. UPAT expression in GC was positively correlated with UHRF1 expression. UHRF1 overexpression offset the inhibitory effects of UPAT down-regulation on cell proliferation, migration, invasion and cell cycle, and partially reversed the positive effect of UPAT down-regulation on apoptosis. CONCLUSION: UPAT might positively regulate the progression of GC via interacting with UHRF1. The UHRF1/UPAT axis revealed in the present study may provide a promising approach to intervene in the progression of GC.
Authors: Thomas Derrien; Rory Johnson; Giovanni Bussotti; Andrea Tanzer; Sarah Djebali; Hagen Tilgner; Gregory Guernec; David Martin; Angelika Merkel; David G Knowles; Julien Lagarde; Lavanya Veeravalli; Xiaoan Ruan; Yijun Ruan; Timo Lassmann; Piero Carninci; James B Brown; Leonard Lipovich; Jose M Gonzalez; Mark Thomas; Carrie A Davis; Ramin Shiekhattar; Thomas R Gingeras; Tim J Hubbard; Cedric Notredame; Jennifer Harrow; Roderic Guigó Journal: Genome Res Date: 2012-09 Impact factor: 9.043