Department of Gastrointestinal Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, PR China.
Department of Obstetrics and Gynecology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, PR China.
Gene. 2019 May 15;696:1-9. doi: 10.1016/j.gene.2018.12.079. Epub 2019 Feb 5.
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.
In this study, the exact biological functions and regulation mechanisms of GAS6-AS1 in gastric cancer (GC) was examined.
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.
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.
作为一类非编码 RNA（lncRNAs）的非编码反义（AS）转录本，其功能特征在于在包括肿瘤生物学在内的各种病理生理过程中发挥关键作用。
在这项研究中，检测了 GAS6-AS1 在胃癌（GC）中的确切生物学功能和调控机制。
GAS6-AS1 在 GC 组织中明显上调，且与 GC 患者的晚期（III+IV 期）相关。功能获得和功能丧失实验表明，GAS6-AS1 通过促进进入 S 期，促进体外细胞增殖、迁移和侵袭能力以及体内异种移植肿瘤生长。机制研究表明，GAS6-AS1 可以通过形成 RNA-RNA 双链，在转录或翻译水平上控制其同源 sense 基因 GAS6 的表达，从而诱导 AXL 水平的增加并驱动 AXL 信号通路的激活。
综上所述，我们的研究表明，GAS6-AS1 通过激活其同源 sense 基因 GAS6，显著驱动 GC 的侵袭表型，并为 GAS6-AS1 作为 GC 潜在治疗靶点提供了更全面的认识。
