Published online Oct 15, 2019. doi: 10.4251/wjgo.v11.i10.842
Peer-review started: May 7, 2019
First decision: June 4, 2019
Revised: June 19, 2019
Accepted: July 26, 2019
Article in press: July 28, 2019
Published online: October 15, 2019
Gastric cancer (GC) is a common type of malignant tumor with poor prognosis and presents a serious threat to human health. In February 2018 , the latest statistics from the Chinese National Cancer Center showed that although the overall incidence of GC is declining, it remains second in terms of incidence among all malignancies in China, just below lung cancer. At present, there is no efficient early diagnosis and curative treatment strategy for GC. As precision medicine is the future direction in cancer therapy, it is important to identify an early diagnostic or therapeutic biomarker of GC.
To explore the expression pattern, biological function and potential mechanism of miRNA (miR)-320a in GC, and to determine whether miR-320a functions as an early diagnostic or therapeutic biomarker in GCaccording to its expression and biological functions.
miR-320a mimic and inhibitor were transfected into GC cells for bidirectional regulation of the expression level of miR-320a. The effect of miR-320a on cell viability, migration, invasion and apoptosis was determined through a series of functional experiments. These results would provide scientific evidence for clinical treatment of GC.
Quantitative real-time polymerase chain reaction (PCR) and Western blotting were performed to determine the levels of related factors. Methylation-specific PCR was applied for analysis of methylation status of the miR-320a promoter CpG islands in GC cell lines and tissues. CCK8, flow cytometry, Transwell invasion and wound healing assays were performed to determine the effect of miR-320a on cell behavior. Dual luciferase assay was performed to identify whether pre-B-cell leukemia homeobox (PBX) 3 was the target gene of miR-320a. TargetScanHuman7.1, miRDB, microrna.org and MethPrimer were used for bioinformatics analysis. Student’s t test (two-tailed) and analysis of variance (ANOVA) were used for statistical analysis.
miR-320a was downregulated in GC, and its expression deficiency was partly due to hypermethylation of the promoter CpG islands. miR-320a overexpression inhibited cell viability, migration and invasion, and induced apoptosis through targeting PBX3 in GC cells. miR-320a functioned as a tumor suppressor in vitro. However, its biological effect in a preclinical model should be further determined.
miR-320a was downregulated in GC tissues and cells, and its abnormal expression was related to GC cell behavior. We confirmed that miR-320a overexpression inhibited cell viability, migration and invasion, and induced apoptosis in GC cells. miR-320a deficiency showed the opposite results. Consistent with previous research, miR-320a functioned as a tumor suppressor. miR-320a could be a biomarker for GC diagnosis and treatment. We found that miR-320a downregulation in GC was due to the elevated methylation level of the miR-320a promoter CpG islands. The elevation was partly reversed by 5-Aza-2’-deoxycytidine and trichostatin A. In addition, PBX3 was firstly identified as the target gene of miR-320a in GC.
For future research, we will focus on the related signaling pathways through which miR-320a regulates GC cell biological behaviors. Screening for related signaling pathways of GC will be performed using the Cancer Genome Atlas database, followed by related factor detection using Western blotting and quantitative real-time PCR. Activator and inhibitor for target signaling will be applied to GC cells, and cell viability, cell cycle, cell migration, invasion and apoptosis will be determined.