MicroRNA-320a suppresses tumor progression by targeting PBX3 in gastric cancer and is downregulated by DNA methylation

• Published in: World journal of gastrointestinal oncology Vol. 11; no. 10; pp. 842 - 856
• Main Authors: Li, Yong-Shuang, Zou, Ying, Dai, Dong-Qiu
• Format: Journal Article
• Language: English
• Published: Baishideng Publishing Group Inc 15.10.2019
• Subjects: Basic Study
• ISSN: 1948-5204; 1948-5204
• DOI: 10.4251/wjgo.v11.i10.842

BACKGROUNDEctopic expression of miRNAs promotes tumor development and progression. miRNA (miR)-320a is downregulated in many cancers, including gastric cancer (GC). However, the mechanism underlying its downregulation and the role of miR-320a in GC are unknown. AIMTo determine expression and biological functions of miR-320a in GC and investigate the underlying molecular mechanisms. METHODSQuantitative real-time polymerase chain reaction (PCR) was used to determine expression of miR-320a in GC cell lines and tissues. TargetScanHuman7.1, miRDB, and microRNA.org were used to predict the possible targets of miR-320a, and a dual luciferase assay was used to confirm the findings. Western blotting was used to detect the protein levels of pre-B-cell leukemia homeobox 3 (PBX3) in GC cells and tissue samples. Cell Counting Kit-8 proliferation, Transwell, wound healing, and apoptosis assays were performed to analyze the biological functions of miR-320a in GC cells. Methylation-specific PCR was used to analyze the methylation level of the miR-320a promoter CpG islands. 5-Aza-2'-deoxycytidine (5-Aza-CdR) and trichostatin A (TSA) were used to treat GC cells. RESULTSmiR-320a expression was lower in GC cell lines and tissues than in the normal gastric mucosa cell line GES-1 and matched adjacent normal tissues. miR-320a overexpression suppressed GC cell proliferation, invasion and migration, and induced apoptosis. PBX3 was a target of miR-320a in GC. The methylation level of the miR-320a promoter CpG islands was elevated and this was partly reversed by 5-Aza-CdR and TSA. CONCLUSIONmiR-320a acts as a tumor suppressor and inhibits malignant behavior of GC cells, partly by targeting PBX3. DNA methylation is an important mechanism associated with low expression of miR-320a.