Yongchao Liu1, Lu Yin2, Chunqiu Chen2, Xiangyu Zhang3, Sheng Wang4. 1. Department of Critical Care Medicine, Shanghai Tenth People's Hospital, Tongji University, Shanghai, China. 2. Center for Diffcult and Complicated Abdominal Surgery, Shanghai Tenth People's Hospital, Tongji University, Shanghai, China. 3. Department of Critical Care Medicine, Shanghai Tenth People's Hospital, Tongji University, Shanghai, China. Electronic address: xiangyu62@126.com. 4. Department of Critical Care Medicine, Shanghai Tenth People's Hospital, Tongji University, Shanghai, China. Electronic address: wangsheng@tongji.edu.cn.
Abstract
BACKGROUND: The rapid progress of gastric cancer (GC) is mainly due to metastasis. Long non-coding RNA (lncRNA) GAS5 has been identified as a tumor suppressor in numerous cancers, and its downregulation in GC has already been reported. AIMS: In this study, we planned to investigate the role of GAS5 in GC metastasis. METHODS: Gene expressions were detected by qRT-PCR. ISH staining was applied to assess GAS5 level in clinical tissues. Gain-of-function assays were conducted to evaluate the function of GAS5 in GC metastasis. RNA pull down, RIP and cycloheximide assays were performed to confirm the relationship between GAS5 and p53 protein. RESULTS: GAS5 expression was markedly decreased in GC tissues and cell lines, and its low expression was strongly related to GC metastasis and unsatisfactory prognosis. GAS5 overexpression repressed GC cell migration and invasion by targeting p53. Intriguingly, GAS5 relied on the exon 12 to interact with and stabilize p53 protein. CONCLUSION: Our data implied that GAS5 is a suppressor in GC metastasis via modulating p53 signaling, suggesting GAS5 as a potential therapeutic target for GC, especially for patients with metastasis.
BACKGROUND: The rapid progress of gastric cancer (GC) is mainly due to metastasis. Long non-coding RNA (lncRNA) GAS5 has been identified as a tumor suppressor in numerous cancers, and its downregulation in GC has already been reported. AIMS: In this study, we planned to investigate the role of GAS5 in GC metastasis. METHODS: Gene expressions were detected by qRT-PCR. ISH staining was applied to assess GAS5 level in clinical tissues. Gain-of-function assays were conducted to evaluate the function of GAS5 in GC metastasis. RNA pull down, RIP and cycloheximide assays were performed to confirm the relationship between GAS5 and p53 protein. RESULTS:GAS5 expression was markedly decreased in GC tissues and cell lines, and its low expression was strongly related to GC metastasis and unsatisfactory prognosis. GAS5 overexpression repressed GC cell migration and invasion by targeting p53. Intriguingly, GAS5 relied on the exon 12 to interact with and stabilize p53 protein. CONCLUSION: Our data implied that GAS5 is a suppressor in GC metastasis via modulating p53 signaling, suggesting GAS5 as a potential therapeutic target for GC, especially for patients with metastasis.