KLF5-Modulated lncRNA NEAT1 Contributes to Tumorigenesis by Acting as a Scaffold for BRG1 to Silence GADD45A in Gastric Cancer.

ABSTRACT: Long noncoding RNAs (lncRNAs), genomic "dark matter," are deeply involved in diverse biological processes. The lncRNA nuclear paraspeckle assembly transcript 1 (NEAT1) is a highly participatory lncRNA; however, its roles in gastric cancer (GC) remain largely unexplored. Here, we demonstrated that the expression of NEAT1 was significantly increased and negatively correlated with prognosis in GC. Subsequent experiments confirmed that KLF5 can induce NEAT1 expression by binding to the NEAT1 promoter region. Further experiments revealed that NEAT1 silencing significantly suppressed cell proliferation both in vitro and in vivo and induced apoptosis. We used mRNA sequencing (mRNA-seq) to identify the preferentially affected genes linked to cell proliferation in cells with NEAT1 knockdown. Mechanistically, NEAT1 bound BRG1 (SMARCA4) directly, modulating H3K27me3 and H3K4me3 in the GADD45A promoter to regulate GADD45A-dependent G2/M cell cycle progression. In addition, BRG1 was significantly upregulated and correlated with outcomes in GC; moreover, it promoted cell proliferation both in vitro and in vivo. Taken together, our data support the importance of NEAT1 in promoting GC tumorigenesis and indicate that NEAT1 might be a diagnostic and therapeutic target in GC.

SUBMITTER: Ma P 

PROVIDER: S-EPMC7533296 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature