Growing evidences illustrated that long non-coding RNAs (lncRNAs) exhibited widespread effects on the progression of human cancers via various mechanisms. Long intergenic non-protein-coding RNA 01446 (LINC01446), a 3484-bp ncRNA, is known to locate at chromosome 7p12.1. However, its biological functions and specific action mechanism in gastric cancer (GC) are still unclear. In our study, LINC01446 was proved to be markedly upregulated in GC tissues relative to the normal tissues, and positively correlated with the poor survival of GC patients. The multivariate Cox regression model showed that LINC01446 functioned as an independent prognostic factor for the survival of GC patients. Functionally, LINC01446 facilitated the proliferation and metastasis of GC cells. Moreover, RNA-seq analysis demonstrated that LINC01446 knockdown primarily regulated the genes relating to the growth and migration of GC. Mechanistically, LINC01446 could widely interact with histone lysine-specific demethylase LSD1 and recruit LSD1 to the Ras-related dexamethasone-induced 1 (RASD1) promoter, thereby suppressing RASD1 transcription. Overall, these findings suggest that LINC01446/LSD1/RASD1 regulatory axis may provide bona fide targets for anti-GC therapies.

越来越多的证据表明，长的非编码RNA（lncRNA）通过各种机制对人类癌症的发展表现出广泛的影响。长的基因间非蛋白质编码RNA 01446（LINC01446）是3484 bp的ncRNA，已知位于染色体7p12.1。然而，其在胃癌（GC）中的生物学功能和特异性作用机制仍不清楚。在我们的研究中，LINC01446被证明在GC组织中相对于正常组织显着上调，并且与GC患者的不良生存率呈正相关。多元Cox回归模型显示LINC01446是GC患者生存的独立预后因素。在功能上，LINC01446促进了GC细胞的增殖和转移。此外，RNA-seq分析表明，LINC01446敲低蛋白主要调控与GC生长和迁移有关的基因。从机理上讲，LINC01446可以与组蛋白赖氨酸特异性脱甲基酶LSD1广泛相​​互作用，并将LSD1募集至Ras相关的地塞米松诱导1（RASD1）启动子，从而抑制RASD1转录。总体而言，这些发现表明LINC01446 / LSD1 / RASD1调控轴可能为抗GC治疗提供真正的靶标。