DSCAM-AS1 Long Non-Coding RNA Exerts Oncogenic Functions in Endometrial Adenocarcinoma via Activation of a Tumor-Promoting Transcriptome Profile

Abstract

Accumulating evidence suggests that lncRNA DSCAM-AS1 acts tumor-promoting in various cancer entities. In breast cancer, DSCAM-AS1 was shown to be the lncRNA being most responsive to induction by estrogen receptor α (ERα). In this study, we examined the function of DSCAM-AS1 in endometrial adenocarcinoma using in silico and different in vitro approaches. Initial analysis of open-source data revealed DSCAM-AS1 overexpression in endometrial cancer (EC) (p < 0.01) and a significant association with shorter overall survival of EC patients (HR = 1.78, p < 0.01). In EC, DSCAM-AS1 was associated with endometrial tumor promotor gene PRL and with expression of ERα and its target genes TFF1 and PGR. Silencing of this lncRNA by RNAi in two EC cell lines was more efficient in ERα-negative HEC-1B cells and reduced their growth and the expression of proliferation activators like NOTCH1, PTK2 and EGR1. DSCAM-AS1 knockdown triggered an anti-tumoral transcriptome response as revealed by Affymetrix microarray analysis, emerging from down-regulation of tumor-promoting genes and induction of tumor-suppressive networks. Finally, several genes regulated upon DSCAM-AS1 silencing in vitro were found to be inversely correlated with this lncRNA in EC tissues. This study clearly suggests an oncogenic function of DSCAM-AS1 in endometrial adenocarcinoma via activation of a tumor-promoting transcriptome profile.

The Promotive and Inhibitory Role of Long Non-Coding RNAs in Endometrial Cancer Course—A Review

“…The overexpression of another lncRNA-DSCAM-AS1 is associated with higher expression levels of the prolactin gene (PRL) and estrogen receptor α (Erα), a more aggressive course of EC, and a shorter survival period of patients. The oncogenic role of DSCAM-AS1 is correlated with the blocking of miR-136-5p actions [ 50 , 51 ]. In other research, it has been shown that VPS9D1-AS1 can contribute to EC progression by binding to miR-520a-5p and promoting the expression of Baculoviral IAP Repeat-Containing 5 (BIRC5).…”

Endocrine nuclear receptors and long non‑coding RNAs reciprocal regulation in cancer (Review)

“…highlighted that DSCAM-AS1 interacts with nuclear ribonucleoprotein (hnRNPL) in BC cells, promoting tumor progression and inducing tamoxifen resistance (49). More recently, Yadav et al (50) demonstrated that progesterone also can induce expression of DSCAM-AS1 and its silencing mimics the effect of progesterone in impeding cell migration and invasion in PR + BC cells.…”

Non-Coding RNAs in Health and Disease: Editorial

“…Additionally, original articles concentrated on different aspects of the biology of ncRNAs. Gargaun et al looked at the possible role of the lncRNA 44s2 and of 45-55 multiexon skipping as therapeutic strategies in Duchenne and Becker muscular dystrophies [6], while Treeck et al identified DSCAM-AS1, a lncRNA with oncogenic roles in endometrial adenocarcinoma, as witnessed by its association with a shorter overall survival of patients affected by this cancer and with the expression of both the endometrial tumor promotor gene prolactin (PRL) and the Estrogen Receptor α (ERα) [7].…”