Published online Mar 14, 2019. doi: 10.3748/wjg.v25.i10.1224
Peer-review started: December 11, 2018
First decision: December 28, 2018
Revised: January 27, 2019
Accepted: January 28, 2019
Article in press: January 28, 2019
Published online: March 14, 2019
Gastric cancer (GC) is one of the most common digestive malignancies and remains the second most common cause of cancer-related mortality worldwide. Currently, most patients are diagnosed at an advanced stage, leading to a low cure rate and a low 5-year survival rate. Therefore, it is necessary to further study the molecular mechanism of GC and identify more effective biomarkers for the diagnosis and treatment of GC.
Accumulating studies have indicated that microRNAs (miRNAs) have been associated with almost all known physiological and pathological processes, including cancer. In addition, it is suggested in recent studies that epigenetic modification, especially DNA methylation, is one of many mechanisms of miRNA suppression in human cancer. A greater understanding of these factors will play an important role in early diagnosis and treatment of GC and improvement of prognosis.
To study the potential role and possible regulatory mechanism of microRNA-596 (miR-596) in GC, and whether other targets of miR-596 exist in GC.
In the present study, the levels of miR-596 expression in 55 pairs of GC and normal control tissues and cell lines were initially assessed using quantitative real-time (qRT-PCR). We further examined the relationship between miR-596 expression and clinicopathological factors in 55 GC tissues by Pearson's χ2 test. In addition, peroxiredoxin 1 (PRDX1) expression was analyzed in 55 paired GC and control tissues and cell lines by qRT-PCR. Western blot and luciferase reporter assay were used to detect the effect of miR-596 on PRDX1 expression. Then, the proliferation, metastasis, and invasion of GC cells transfected with miR-596 mimics were analyzed, respectively, by Cell Counting Kit-8 proliferation assay, wound healing assay, and transwell invasion assay. The methylation status of the promoter CpG islands of miR-596 in GC cell lines was detected by methylation-specific PCR. Meanwhile, we treated GC cells with the demethylating agent 5-Aza-2’-deoxycytidine (5-Aza-dC) to confirm whether miR-596 expression could be restarted. Finally, in order to evaluate whether 5-Aza-dC treatment affects GC cell growth, we analyzed the proliferation of GC cells treated with 5-Aza-dC.
Our current study demonstrated that the expression of miR-596 was downregulated in GC cells and GC tissues. The in vitro data further suggested that miR-596 expression was able to inhibit GC cell growth, migration, and invasion. Furthermore, miR-596 expression was regulated by epigenetic mechanisms. Moreover, we identified that PRDX1 is one of the putative target genes of miR-596.
In the present study, we have investigated a suppressive role of microRNA-596 in GC. We reported that miR-596 was downregulated in human specimens of GC and GC cell lines, and that overexpression of miR-596 significantly reduced GC cell proliferation. Moreover, the downregulation of miR-596 in GC cell lines was associated with an increase of miR-596 promoter methylation. We also established that miR-596 controls the expression of PRDX1, which has never been reported before, suggesting that this interaction could play an important role in GC progression.
Our results further emphasize that miR-596 functions as a crucial tumor suppressor that is regulated by epigenetic mechanisms in GC and may offer a promising novel therapeutic approach for GC. Nonetheless, more studies are required to determine the precise mechanism of miR-596 in the progression of GC.