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

Bibliographic Details
Title: KLF5-Modulated lncRNA NEAT1 Contributes to Tumorigenesis by Acting as a Scaffold for BRG1 to Silence GADD45A in Gastric Cancer
Authors: Pei Ma, Yutian Pan, Fan Yang, Yuan Fang, Weitao Liu, Chenhui Zhao, Tao Yu, Mengyan Xie, Xingming Jing, Xi Wu, Chongqi Sun, Wei Li, Tongpeng Xu, Yongqian Shu
Source: Molecular Therapy: Nucleic Acids, Vol 22, Iss , Pp 382-395 (2020)
Publisher Information: Elsevier, 2020.
Publication Year: 2020
Collection: LCC:Therapeutics. Pharmacology
Subject Terms: NEAT1, tumorigenesis, prognosis, gastric cancer, epigenetics, Therapeutics. Pharmacology, RM1-950
More Details: 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.
Document Type: article
File Description: electronic resource
Language: English
ISSN: 2162-2531
Relation: http://www.sciencedirect.com/science/article/pii/S2162253120302742; https://doaj.org/toc/2162-2531
DOI: 10.1016/j.omtn.2020.09.003
Access URL: https://doaj.org/article/88700aba02ce4dffae02991d168a3038
Accession Number: edsdoj.88700aba02ce4dffae02991d168a3038
Database: Directory of Open Access Journals
More Details
ISSN:21622531
DOI:10.1016/j.omtn.2020.09.003
Published in:Molecular Therapy: Nucleic Acids
Language:English