OPA-interacting protein 5 antisense transcript 1 (OIP5-AS1) plays an important regulatory role in various types of cancers. However, the functional role and regulatory mechanisms of OIP5-AS1 in gastric cancer (GC) remain largely unknown. In this study, we found that the expression of OIP5-AS1 was increased in GC tissues compared with that in adjacent non-cancerous tissues, which was significantly associated with shorter overall survival time of patients. In addition, OIP5-AS1 expression was also increased in GC cell lines including NCI-N87, MKN-45, BGC-823 and SGC-7901, when compared with that in normal gastric epithelial cell line GES-1. Knockdown of OIP5-AS1 markedly suppressed the proliferation and colony formation activities of GC cells, induced G0/G1 arrest and apoptosis of GC cells in vitro, and restrained tumor growth in vivo. Mechanistically, OIP5-AS1 functions as an oncogenic competing endogenous RNA by binding to and sequestering miR-422a to elevate the expression of anoctamin-1. Our study first demonstrated that OIP5-AS1 is a critical and powerful regulator of GC pathogenesis and may represent a novel candidate target for GC therapy.

中文翻译：

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LncRNA OIP5-AS1通过靶向miR-422a / ANO1轴促进胃癌细胞的生长。

与OPA相互作用的蛋白5反义转录本1（OIP5-AS1）在各种类型的癌症中起着重要的调节作用。但是，OIP5-AS1在胃癌（GC）中的功能作用和调节机制仍然未知。在这项研究中，我们发现与相邻的非癌性组织相比，GC组织中OIP5-AS1的表达增加，这与患者总体生存时间的缩短显着相关。另外，与在正常胃上皮细胞系GES-1中相比，在包括NCI-N87，MKN-45，BGC-823和SGC-7901的GC细胞系中，OIP5-AS1的表达也增加了。抑制OIP5-AS1可以显着抑制GC细胞的增殖和集落形成活性，在体外诱导GC细胞的G0 / G1阻滞和凋亡，并在体内抑制肿瘤的生长。从机理上讲，OIP5-AS1通过与miR-422a结合并螯合miR-422a以提高anoctamin-1的表达而起竞争性内源性RNA的作用。我们的研究首次证明，OIP5-AS1是GC发病机制的关键且功能强大的调节剂，可能代表了GC治疗的新候选靶点。