Peichen Zhang1, Qiantong Dong1, Hua Zhu2, Shi Li3, Lingyan Shi4, Xiangjian Chen5. 1. Department of Gastrointestinal Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, PR China. 2. Department of Obstetrics and Gynecology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, PR China. 3. Department of Urology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, PR China. 4. Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, PR China. Electronic address: shilingyan@wmu.edu.cn. 5. Department of Gastrointestinal Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, PR China. Electronic address: wz1370666@126.com.
Abstract
OBJECTIVE: As one broader class of non-coding RNAs (lncRNAs), non-coding antisense (AS) transcripts are functionally characterized to play pivotal roles in various pathophysiological processes, including tumor biology. METHODS: In this study, the exact biological functions and regulation mechanisms of GAS6-AS1 in gastric cancer (GC) was examined. RESULTS: The expression of GAS6-AS1 was markedly upregulated in GC tissues and is associated with advanced stage (III + IV) of GC patients. Gain-of-function and loss-of-function experiments showed that GAS6-AS1 promoted cell proliferation, migration, invasion ability in vitro and xenograft tumor growth in vivo by promoting entry into S-phase. The mechanistic investigations showed that GAS6-AS1 can control the expression of its cognate sense gene GAS6 at the transcriptional or translational levels by forming a RNA-RNA duplex, consequently inducing an increase of AXL level and driveling AXL signaling pathway activation. CONCLUSIONS: Taken together, our studies indicate that GAS6-AS1 significantly driving the aggressive phenotype in GC through activating its cognate sense gene GAS6, and provides a more complete understanding of GAS6-AS1 as a potential therapeutic target for GC.
OBJECTIVE: As one broader class of non-coding RNAs (lncRNAs), non-coding antisense (AS) transcripts are functionally characterized to play pivotal roles in various pathophysiological processes, including tumor biology. METHODS: In this study, the exact biological functions and regulation mechanisms of GAS6-AS1 in gastric cancer (GC) was examined. RESULTS: The expression of GAS6-AS1 was markedly upregulated in GC tissues and is associated with advanced stage (III + IV) of GC patients. Gain-of-function and loss-of-function experiments showed that GAS6-AS1 promoted cell proliferation, migration, invasion ability in vitro and xenograft tumor growth in vivo by promoting entry into S-phase. The mechanistic investigations showed that GAS6-AS1 can control the expression of its cognate sense gene GAS6 at the transcriptional or translational levels by forming a RNA-RNA duplex, consequently inducing an increase of AXL level and driveling AXL signaling pathway activation. CONCLUSIONS: Taken together, our studies indicate that GAS6-AS1 significantly driving the aggressive phenotype in GC through activating its cognate sense gene GAS6, and provides a more complete understanding of GAS6-AS1 as a potential therapeutic target for GC.
Authors: Jie Chai; Jianbo Zhang; Dali Han; Wei Dong; Li Han; Lei Zou; Bin Feng; Baosheng Li; Wanli Ma Journal: Oncol Lett Date: 2020-05-21 Impact factor: 2.967
Authors: Carlo Smirne; Cristina Rigamonti; Carla De Benedittis; Pier Paolo Sainaghi; Mattia Bellan; Michela Emma Burlone; Luigi Mario Castello; Gian Carlo Avanzi Journal: Dis Markers Date: 2019-09-08 Impact factor: 3.434