Despite the decreased incidence of GC, it is still a major human health concern. Exploration of pathogenic molecular mechanisms underlying GC is still needed for early detection of GC and decline its mortality rates [30]. Since lncRNAs are involved in gene regulation, they have received increasing attention recently [21]. Additionally, aberrant expression of lncRNAs is associated with the development and progression of numerous cancers, including GC [21, 24].
Accordingly, to study the association of DLGAP1-AS2 with gastric tumorigenesis, we first analyzed microarray expression datasets from the GEO database to evaluate the DLGAP1-AS2 expression level in GC and normal tissues. DLGAP1-AS2 expression was found to be elevated in GC cases compared to normal samples. Also, the qPCR analysis data revealed that DLGAP1-AS2 was significantly upregulated in GC tissue specimens compared to paired normal samples. Another layer of confirmation came from analyzing the TCGA-STAD dataset. An interesting and unexpected finding was the negative correlation between DLGAP1-AS2 expression level and the patients' age, which is controversial and needs further investigation. Also, the relative expression level of DLGAP1-AS2 in GC tissue samples was significantly correlated with lymphatic and vascular invasion. Therefore, our findings indicate that the DLGAP1-AS2 overexpression might be associated with GC progression and metastasis and suggest the possible oncogenic role of DLGAP1-AS2 in GC as well.
Additionally, further analysis DLGAP1-AS2 expression in other prevalent malignancies using TCGA, illustrated this lncRNA is also upregulated in breast, colorectal, and prostate cancer specimens compared to normal samples, indicating a promising role of DLGAP1-AS2 as an oncogene through tumorigenesis of human cancers. In line with our findings, Liu et al. observed the up-regulation of DLGAP1-AS2 in CCA cell lines. Additionally, they found that DLGAP1-AS2 contributes to CCA progression by modulating the miR-505/GALNT10 cascade [28]. Recently the overexpression of DLGAP1-AS2 and down-regulation of miR-154-5P was observed in patients with HCC. Further investigations identified that DLGAP1-AS2 knockdown in HCC cells resulted in decreased methylation and overexpression of miR-154-5p, consequently inhibition of HCC cell invasion and migration. Therefore, these findings provided clues that DLGAP1-AS2 might play a role as an oncogene in HCC [27]. Miao et al. found that DLGAP1-AS2 was overexpressed in glioma patients. They revealed that DLGAP1-AS2 depletion in glioma cells promoted cell apoptosis and inhibited cell proliferation as well as cell migration, which consequently attenuated the progression of glioma. Also, YAP1 expression was downregulated in these cells. Thereby, YAP1 was considered a downstream target of DLGAP1-AS2 and appears to play a biological role in glioma progression. These findings thus support the view that DLGAP1-AS2 might function as an oncogene in glioma progression [26]. Several lines of evidence from different studies have identified YAP1 as an oncogene in numerous cancers. Besides, overexpression of YAP1 has been identified in GC. Further investigations have revealed that up-regulation of YAP1 could promote cell proliferation, growth, and migration in GC and associates with the progression and lymph node metastasis of GC as well. Consequently, these findings demonstrate that YAP1 functions as an oncogene in GC [31–35].
It is noteworthy that we found a significant correlation between DLGAP1-AS2 and YAP1 expression in TCGA dataset by Pearson’s correlation analysis. According to the previous studies and the correlation between DLGAP1-AS2 and YAP1 expression, YAP1 might be the downstream target of DLGAP1-AS2 in GC progression and invasion. Further investigations are required to identify the molecular mechanisms by which DLGAP1-AS2 contributes to the GC progression. According to the ROC curve analysis, DLGAP1-AS2 overexpression may be suggested as a potential diagnostic target for discriminating GC and normal cases (p < 0. 0001, AUC = 0.8920).