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长链非编码RNA DLGAP1-AS1通过作为微小RNA-628-5p的竞争性内源性RNA并上调星形胶质细胞上调基因1的表达来促进胃癌的侵袭性。

Long Noncoding RNA DLGAP1-AS1 Promotes the Aggressive Behavior of Gastric Cancer by Acting as a ceRNA for microRNA-628-5p and Raising Astrocyte Elevated Gene 1 Expression.

作者信息

Deng Jiying, Zhang Qin, Lu Lianwei, Fan Chunxia

机构信息

Department of General Surgery, Gaomi People's Hospital, Gaomi, Shandong 261500, People's Republic of China.

Department of Neurosurgery, Gaomi People's Hospital, Gaomi, Shandong 261500, People's Republic of China.

出版信息

Cancer Manag Res. 2020 Apr 29;12:2947-2960. doi: 10.2147/CMAR.S246166. eCollection 2020.

DOI:10.2147/CMAR.S246166
PMID:32431541
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7197941/
Abstract

PURPOSE

The long noncoding RNA DLGAP1 antisense RNA 1 (DLGAP1-AS1) plays well-defined roles in the malignant progression of hepatocellular carcinoma. The purpose of this study was to determine whether DLGAP1-AS1 affects the aggressive behavior of gastric cancer (GC).

METHODS

DLGAP1-AS1 expression in GC tissue samples and cell lines was determined by reverse-transcription quantitative PCR. GC cell proliferation, apoptosis, migration, invasion, and tumor growth in vitro as well as in vivo were examined by the Cell Counting Kit-8 assay, flow-cytometric analysis, transwell migration and invasion assays, and xenograft model experiments, respectively.

RESULTS

DLGAP1-AS1 was overexpressed in GC tissue samples and cell lines. Among patients with GC, the increased level of DLGAP1-AS1 correlated with tumor size, TNM stage, lymph node metastasis, distant metastasis, and shorter overall survival. The knockdown of DLGAP1-AS1 suppressed GC cell proliferation, migration, and invasion in vitro, as well as promoted cell apoptosis and hindered tumor growth in vivo. Mechanistically, DLGAP1-AS1 functioned as a competing endogenous RNA for microRNA-628-5p (miR-628-5p) in GC cells, thereby increasing the expression of the miR-628-5p target astrocyte elevated gene 1 (AEG-1). Functionally, the recovery of the miR-628-5p/AEG-1 axis output attenuated the effects of DLGAP1-AS1 knockdown in GC cells.

CONCLUSION

DLGAP1-AS1 is a pleiotropic oncogenic lncRNA in GC. DLGAP1-AS1 plays a pivotal part in the oncogenicity of GC in vitro and in vivo by regulating the miR-628-5p/AEG-1 axis. DLGAP1-AS1, miR-628-5p, and AEG-1 form a regulatory pathway to facilitate GC progression, suggesting this pathway as an effective target for the treatment of GC.

摘要

目的

长链非编码RNA DLGAP1反义RNA 1(DLGAP1-AS1)在肝细胞癌的恶性进展中发挥着明确的作用。本研究旨在确定DLGAP1-AS1是否影响胃癌(GC)的侵袭行为。

方法

通过逆转录定量PCR检测GC组织样本和细胞系中DLGAP1-AS1的表达。分别采用细胞计数试剂盒-8法、流式细胞术分析、Transwell迁移和侵袭实验以及异种移植模型实验检测GC细胞在体外和体内的增殖、凋亡、迁移、侵袭及肿瘤生长情况。

结果

DLGAP1-AS1在GC组织样本和细胞系中高表达。在GC患者中,DLGAP1-AS1水平升高与肿瘤大小、TNM分期、淋巴结转移、远处转移及较短的总生存期相关。敲低DLGAP1-AS1可抑制GC细胞在体外的增殖、迁移和侵袭,并促进细胞凋亡,在体内则抑制肿瘤生长。机制上,DLGAP1-AS1在GC细胞中作为微小RNA-628-5p(miR-628-5p)的竞争性内源性RNA发挥作用,从而增加miR-628-5p靶标星形胶质细胞上调基因1(AEG-1)的表达。功能上,miR-628-5p/AEG-1轴输出的恢复减弱了DLGAP1-AS1敲低对GC细胞的影响。

结论

DLGAP1-AS

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3535/7197941/a3830481a418/CMAR-12-2947-g0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3535/7197941/b8bb2e140172/CMAR-12-2947-g0001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3535/7197941/fd39bd3b7183/CMAR-12-2947-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3535/7197941/daf99d6477b8/CMAR-12-2947-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3535/7197941/a3830481a418/CMAR-12-2947-g0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3535/7197941/b8bb2e140172/CMAR-12-2947-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3535/7197941/85101cfeef87/CMAR-12-2947-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3535/7197941/5eec3ef2e353/CMAR-12-2947-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3535/7197941/96b64f9705fc/CMAR-12-2947-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3535/7197941/fd39bd3b7183/CMAR-12-2947-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3535/7197941/daf99d6477b8/CMAR-12-2947-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3535/7197941/a3830481a418/CMAR-12-2947-g0007.jpg

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