Long Noncoding RNA RGMB-AS1 Acts as a microRNA-574 Sponge Thereby Enhancing the Aggressiveness of Gastric Cancer via HDAC4 Upregulation

• Main Authors: Wang X, Chen X, Tian Y, Jiang D, Song Y
• Format: Article
• Language: English
• Published: Dove Medical Press 2020-02-01
• Series: OncoTargets and Therapy
• Subjects: tumor therapy; gastric cancer; mir-574; rgmb-as1; histone deacetylase 4
• Online Access: https://www.dovepress.com/long-noncoding-rna-rgmb-as1-acts-as-a-microrna-574-sponge-thereby-enha-peer-reviewed-article-OTT

Xiaodong Wang, Xin Chen, Yueli Tian, Dongqiang Jiang, Ying Song Department of Gastroenterology and Digestive Endoscopy Center, The Second Hospital of Jilin University, Changchun, Jilin 130041, People’s Republic of ChinaCorrespondence: Ying SongDepartment of Gastroenterology and Digestive Endoscopy Center, The Second Hospital of Jilin University, 218 Ziqiang Road, Changchun, Jilin 130041, People’s Republic of ChinaEmail [e-mail]: The long noncoding RNA RGMB-AS1 plays an important part in the genesis and progression of multiple human cancers. Nonetheless, little is known regarding its expression, roles, and mechanisms of action in gastric cancer (GC). This study was aimed at investigating the relationship between RGMB-AS1 and GC and illustrating the mechanisms of action of RGMB-AS1 therein.Methods: RGMB-AS1 expression in GC was measured via reverse-transcription quantitative PCR. A series of experiments including Cell Counting Kit-8 assay, flow-cytometric analysis of apoptosis, Transwell migration and invasion assays, and in vivo tumorigenesis experiment were conducted to test the effects of RGMB-AS1 on the malignant phenotype of GC cells. The molecular events behind the oncogenic actions of RGMB-AS1 in GC were elucidated through subcellular fractionation, RNA immunoprecipitation assay, bioinformatics analysis and luciferase reporter assay.Results: RGMB-AS1 upregulation was confirmed in GC tissues and cell lines. Higher RGMB-AS1 expression was associated with adverse clinical parameters and negatively correlated with patient overall survival. RGMB-AS1 knockdown inhibited GC cell proliferation, facilitated apoptosis, and reduced migration and invasion in vitro. Further experiments revealed that RGMB-AS1 knockdown decreased the tumor growth of GC cells in vivo. Mechanistically, RGMB-AS1 functioned as a competing endogenous RNA upregulating histone deacetylase 4 (HDAC4) by sponging microRNA-574 (miR-574). Rescue experiments indicated that miR-574 inhibition and HDAC4 reintroduction reversed the effects of the RGMB-AS1 knockdown on GC cells.Conclusion: The RGMB-AS1–miR-574–HDAC4 regulatory network contributes to the malignancy of GC, thereby offering a novel target for the diagnosis, prognosis, and/or treatment of GC.Keywords: tumor therapy, gastric cancer, miR-574, RGMB-AS1, histone deacetylase 4