This study explored the interplay between DLGAP1-AS2 and the axis of miR-503/cyclin D1 in NSCLC. The results showed that DLGAP1-AS2 was overexpressed in NSCLC and promoted NSCLC cell proliferation by upregulating cyclin D1 by sponging miR-503.
The functionality of DLGAP1-AS2 has only been analyzed in glioma [
13]. It was observed that DLGAP1-AS2 was overexpressed in glioma and upregulated YAP1 to promote glioma cell proliferation and metastasis [
13]. However, the involvement of DLGAP1-AS2 in other cancers remains unclear. In this study, we showed that DLGAP1-AS2 was significantly overexpressed in NSCLC, and DLGAP1-AS2 overexpression increased the proliferation rate of NSCLC cells, indicating DLGAP1-AS2 overexpression in NSCLC may play oncogenic roles by enhancing cancer cell proliferation.
Despite the efforts made on NSCLC treatment, the overall survival of NSCLC patients remains poor [
17,
18]. We found that high DLGAP1-AS2 expression levels were closely correlated with the poor survival of NSCLC patients. Therefore, measuring DLGAP1-AS2 expression levels in cancer tissues might provide guidance for developing personalized therapy, thereby improving patients’ survival. However, clinical trials are needed to verify our hypothesis.
MiR-503 plays different roles in different types of cancers [
14,
19]. For instance, miR-503 is overexpressed in colorectal cancer and promotes cancer progression [
19]. Cyclin D1, a target of miR-503 plays a critical role in various cancers. Jiang et al. found that miR-503 downregulation promotes proliferation, migration, and invasion of esophageal squamous cell carcinoma (ESCC) cells by targeting cyclin D1 [
14]; Long et al. found that miR-503 inhibits human breast cancer cell proliferation by suppressing cyclin D1 expression (
20); Xu et al. [
21] found that miR-503 suppresses endometrioid endometrial cancer cell proliferation and cycle progression by negatively regulating cyclin D1. However, the role of miR-503 by targeting cyclin D1 is unclear in NSCLC. Therefore, in this study, we chose cyclin D1 as a potential target and showed that miR-503 might also target cyclin D1 in NSCLC cells to decrease cell proliferation. We found DLGAP1-AS2 directly interacts with miR-503 to regulate the cyclin D1 expression but has no effect on miR-503 expression. A similar phenomenon has been found in other lncRNAs. Yang et al. [
22] showed that lncRNA MIR31HG functions as a miR-193b sponge but has no significant effects on miR-193b level following MIR31HG knockdown or overexpression. Yang et al. also showed that miR-193b overexpression suppresses MIR31HG expression and function, suggesting that MIR31HG is a target of miR-193b. However, in our study, miR-503 overexpression has no effect on DLGAP1-AS2 expression, suggesting that DLGAP1-AS2 is unlikely a target of miR-503. Therefore, miR503 overexpression inhibits H2170 cell proliferation by downregulating cyclin D1 expression, and DLGAP1-AS2 overexpression may act as a 'sponge' by competing for miR-503 binding to upregulate cyclin D1 expression, thereby promoting H2170 cell proliferation. Overall, our study showed that DLGAP1-AS2 overexpression reduces the effects of miR-503 overexpression on cyclin D1 expression and cell proliferation. Therefore, DLGAP1-AS2 may sponge miR-503 in NSCLC.