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pmid:31837602

LncRNA MAGI2-AS3 Is Regulated by BRD4 and Promotes Gastric Cancer Progression via Maintaining ZEB1 Overexpression by Sponging miR-141/200a.

Dandan Li · Jingjie Wang · Meixin Zhang · Xinhui Hu · Jiajun She · Xuemei Qiu · Xudong Zhang · Li Xu · Ying Liu · Shanshan Qin

Molecular therapy. Nucleic acids · 2020 doi:10.1016/j.omtn.2019.11.003

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Experiment

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Data

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Analysis

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Execution

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Record details sci_version · id · kind · revision · content_hash · schema · created_at · updated_at · generator
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title
LncRNA MAGI2-AS3 Is Regulated by BRD4 and Promotes Gastric Cancer Progression via Maintaining ZEB1 Overexpression by Sponging miR-141/200a.
doi
10.1016/j.omtn.2019.11.003
pmid
31837602
authors array · 10 items
[0]
Dandan Li
[1]
Jingjie Wang
[2]
Meixin Zhang
[3]
Xinhui Hu
[4]
Jiajun She
[5]
Xuemei Qiu
[6]
Xudong Zhang
[7]
Li Xu
[8]
Ying Liu
[9]
Shanshan Qin
journal
Molecular therapy. Nucleic acids
year
2020
abstract
Long non-coding RNAs (lncRNAs) play critical roles in tumorigenesis and tumor progression. However, the biological function of most lncRNAs remains unknown in human gastric cancer. This study here aims to explore the unknown function of lncRNA MAGI2-AS3 in gastric cancer. First, bioinformatics analysis showed that lncRNA MAGI2-AS3 was overexpressed in gastric cancer tissues, and the overexpression of MAGI2-AS3 has been shown to be associated with poor prognosis in all three independent gastric cancer cohorts (The Cancer Genome Atlas stomach cancer [TCGA_STAD], GEO: GSE62254 and GSE15459). The multivariate analysis indicated that lncRNA MAGI2-AS3 was an independent prognostic factor for both overall survival and disease-free survival of gastric cancer patients. Moreover, MAGI2-AS3 was identified to be an epithelial-mesenchymal transition (EMT)-related lncRNA and was highly co-expressed with ZEB1/2 in both gastric cancer tissues and normal stomach tissues. Loss-of-function and gain-of-function studies showed that lncRNA MAGI2-AS3 could positively regulate ZEB1 expression and the process of cell migration and invasion in gastric cancer. Subcellular location assay showed that lncRNA MAGI2-AS3 was mainly located in the cytoplasm of gastric cancer cells. Bioinformatics analysis and functional experiments revealed that lncRNA MAGI2-AS3 was negatively correlated with miR-141/200a expression and negatively regulated miR-141/200a-3p expression in gastric cancer. Therefore, we speculate that lncRNA MAGI2-AS3 promotes tumor progression through sponging miR-141/200a and maintaining overexpression of ZEB1 in gastric cancer. Nevertheless, we identified that BRD4 is a transcriptional regulator of lncRNA MAGI2-AS3 in gastric cancer. Additionally, our findings highlight that lncRNA MAGI2-AS3 is an ideal biomarker and could be a potential therapeutic target for gastric cancer.
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Survival curves were calculated using the Kaplan-Meier method, and differences between the curves were analyzed using the log rank test. A Cox proportional hazards model was used for multivariate survival analysis.
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Survival curves were calculated using the Kaplan-Meier method, and differences between the curves were analyzed using the log rank test. A Cox proportional hazards model was used for multivariate survival analysis.
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RNA-seq data of 407 gastric cancer samples, miRNA-seq data of 491 gastric cancer samples, and the correlated clinical information of 443 gastric cancer samples were downloaded from The Cancer Genome Atlas (TCGA) by using SangerBox software (http://sangerbox.com/) developed by ShengXinRen (https://shengxin.ren/).
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The Cox Regression Analysis for Overall Survival (OVS) and Disease-free Survival (DFS) in TCGA Gastric Cancer Cohort
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MAGI2-AS3 Overexpression Predicts Poor Prognosis of Patients from TCGA Gastric Cancer Cohort
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MAGI2-AS3 Overexpression Predicts a Poor Prognosis of Gastric Cancer Patients in the ACRG Cohort
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RNA-seq data of 407 gastric cancer samples, miRNA-seq data of 491 gastric cancer samples, and the correlated clinical information of 443 gastric cancer samples were downloaded from The Cancer Genome Atlas (TCGA) by using SangerBox software (http://sangerbox.com/) developed by ShengXinRen (https://shengxin.ren/).
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ed a comprehensive transcriptome analysis of RNA-seq data from 373 gastric cancer tissues with co
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t available.aP < 0.05. Materials and Methods RNA-Seq Data Analysis of Stomach Cancer in TCGA RNA-
[2]
gastric cancer, we performed a comprehensive transcriptome analysis of RNA-seq data from 373 gastric ca
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-Seq Data Analysis of Stomach Cancer in TCGA RNA-seq data of 407 gastric cancer samples, miRNA-se
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http://www.cbioportal.org/).37 Cell Culture, Transfection, and Treatment The human gastric cancer cell
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0.03% glutamine at 37°C in 5% CO2. For siRNA transfection: the siRNAs were designed and synthesized by
[2]
ncer cells were grown in six-well plates and transfected by Lipofectamine 2000 (Invitrogen) according
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he manufacturer’s instructions. At 48 h post-transfection, cells were harvested for qPCR analysis. For
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(Shanghai, China). All of the gastric cancer cell lines were cultured in DMEM containing 10% fetal bovine serum (F
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). All of the gastric cancer cell lines were cultured in DMEM containing 10% fetal bovine serum (FBS)
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post-transfection, cells were harvested for qPCR analysis. For lncRNA MAGI2-AS3 overexpressio
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d DMSO. After 24 h, cells were harvested for qPCR analysis. Statistical Analysis For gene expr
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Survival curves were calculated using the Kaplan-Meier method, and differences between the curves were analyzed using the log rank test. A Cox proportional hazards model was used for multivariate survival analysis.
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Complete file 
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However, the biological function of most lncRNAs remains unknown in human gastric cancer. This study here aims to explore the unknown function of lncRNA MAGI2-AS3 in gastric cancer. First, bioinformatics analysis showed that lncRNA MAGI2-AS3 was overexpressed in gastric cancer tissues, and the overexpression of MAGI2-AS3 has been shown to be associated with poor prognosis in all three independent gastric cancer cohorts (The Cancer Genome Atlas stomach cancer [TCGA_STAD], GEO: GSE62254 and GSE15459). The multivariate analysis indicated that lncRNA MAGI2-AS3 was an independent prognostic factor for both overall survival and disease-free survival of gastric cancer patients. Moreover, MAGI2-AS3 was identified to be an epithelial-mesenchymal transition (EMT)-related lncRNA and was highly co-expressed with ZEB1/2 in both gastric cancer tissues and normal stomach tissues. Loss-of-function and gain-of-function studies showed that lncRNA MAGI2-AS3 could positively regulate ZEB1 expression and the process of cell migration and invasion in gastric cancer. Subcellular location assay showed that lncRNA MAGI2-AS3 was mainly located in the cytoplasm of gastric cancer cells. Bioinformatics analysis and functional experiments revealed that lncRNA MAGI2-AS3 was negatively correlated with miR-141/200a expression and negatively regulated miR-141/200a-3p expression in gastric cancer. Therefore, we speculate that lncRNA MAGI2-AS3 promotes tumor progression through sponging miR-141/200a and maintaining overexpression of ZEB1 in gastric cancer. Nevertheless, we identified that BRD4 is a transcriptional regulator of lncRNA MAGI2-AS3 in gastric cancer. 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