Gastric cancer (GC) is one of the most common malignancies of the digestive system worldwide. Multiple long noncoding RNAs (lncRNAs) participate in the regulation of GC development and metastasis. In this study, we aimed to elucidate the expression and function of lncRNA IGFL2-AS1 in GC. We found that IGFL2-AS1 was highly expressed in GC tissues and cell lines. Knockdown of IGFL2-AS1 suppressed GC cell proliferation, migration, and invasion in vitro. Furthermore, we identified that IGFL2-AS1 exerted its function as a molecular sponge of miR-802. MiR-802 was demonstrated to be a tumor suppressor, and overexpression of miR-802 suppressed GC cell growth, migration, and invasion. Mechanistically, we revealed that the cAMP-regulated phosphoprotein 19 (ARPP19) was a direct target of miR-802 and could reverse the inhibitory function of miR-802. Moreover, our results confirmed that knockdown of IGFL2-AS1 inhibited GC tumor development in an in vivo GC tumor xenograft model. In summary, our data suggest that the IGFL2-AS1/miR-802/ARPP19 axis plays a critical role in the progression and metastasis of GC. Therapies targeting the IGFL2-AS1/miR-802/ARPP19 axis can potentially improve GC treatment.

中文翻译：

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LncRNA IGFL2-AS1通过竞争性结合miR-802在胃癌中作为ceRNA调控ARPP19。

胃癌（GC）是全世界消化系统最常见的恶性肿瘤之一。多个长的非编码RNA（lncRNA）参与GC发育和转移的调节。在这项研究中，我们旨在阐明lncRNA IGFL2-AS1在GC中的表达和功能。我们发现IGFL2-AS1在GC组织和细胞系中高表达。击倒IGFL2-AS1抑制了体外GC细胞的增殖，迁移和侵袭。此外，我们发现IGFL2-AS1发挥了miR-802分子海绵的功能。已证明MiR-802是一种肿瘤抑制因子，miR-802的过表达抑制了GC细胞的生长，迁移和侵袭。从机理上讲，我们发现cAMP调节的磷蛋白19（ARPP19）是miR-802的直接靶标，并且可以逆转miR-802的抑制功能。此外，我们的结果证实，在体内GC肿瘤异种移植模型中，IGFL2-AS1的敲低抑制了GC肿瘤的发展。总之，我们的数据表明IGFL2-AS1 / miR-802 / ARPP19轴在GC的进展和转移中起着至关重要的作用。针对IGFL2-AS1 / miR-802 / ARPP19轴的疗法可能会改善GC治疗。