Dysregulation of microRNAs (miRNAs or miRs) is implicated in the development of gastric cancer (GC), which is possibly related to their roles in targeting tumor-suppressive or tumor-promoting genes. 本研究旨在确定miR-488在胃癌中的功能和调节机制。首先，对人类GC细胞进行miRNA功能增强或减弱、RNA干扰或过表达的体外恶性评估。同时，在裸鼠模型中评估了肿瘤发生和肝转移情况。结果表明，miR-488升高可以抑制GC（MKN-45和OCUM-1）的细胞增殖、迁移和侵袭，并在体内减少它们的肿瘤发生和肝转移。荧光素酶检测表明，miR-488与HULC结合并抑制其表达。此外，HULC可以增强EZH2-H3K27me3在p53启动子区域的富集，并根据RIP和ChIP-qPCR检测数据表明，通过表观遗传学机制抑制p53表达。此外，验证了HULC可以增强GC的生长和转移性。总体来说，miR-488抑制可导致HULC重新表达，并增强EZH2-H3K27me3在p53启动子区域的富集并抑制p53表达，从而促进GC的生长和转移。©2022年。作者在Springer Nature B.V.的独家许可下发表。

Dysregulation of microRNAs (miRNAs or miRs) is implicated in the development of gastric cancer (GC), which is possibly related to their roles in targeting tumor-suppressive or tumor-promoting genes. Herein, the current study was intended to ascertain the function of miR-488 and its modulatory mechanism in GC. Initially, human GC cells were assayed for their in vitro malignancy after miRNA gain- or loss-of-function and RNA interference or overexpression. Also, tumorigenesis and liver metastasis were evaluated in nude mouse models. Results demonstrated that miR-488 elevation suppressed GC (MKN-45 and OCUM-1) cell proliferation, migration, and invasiveness in vitro and reduced their tumorigenesis and liver metastasis in vivo. The luciferase assay identified that miR-488 bound to HULC and inhibited its expression. Furthermore, HULC could enhance EZH2-H3K27me3 enrichment at the p53 promoter region and epigenetically repress the p53 expression based on the data from RIP- and ChIP-qPCR assay. Additionally, HULC was validated to enhance GC growth and metastasis in vitro and in vivo. Overall, HULC re-expression elicited by miR-488 inhibition can enhance EZH2-H3K27me3 enrichment in the p53 promoter and repress the p53 expression, thus promoting the growth and metastasis of GC.© 2022. The Author(s), under exclusive licence to Springer Nature B.V.