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

Treeck, Oliver and Weber, Florian and Fritsch, Juergen and Skrzypczak, Maciej and Schueler-Toprak, Susanne and Buechler, Christa and Ortmann, Olaf (2022) DSCAM-AS1 Long Non-Coding RNA Exerts Oncogenic Functions in Endometrial Adenocarcinoma via Activation of a Tumor-Promoting Transcriptome Profile. BIOMEDICINES, 10 (7): 1727. ISSN , 2227-9059

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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 alpha (ER alpha). 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 ERoc and its target genes TFF1 and PGR. Silencing of this lncRNA by RNAi in two EC cell lines was more efficient in ER alpha-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.

Item Type: Article
Uncontrolled Keywords: CELL LUNG-CANCER; HEPATOCELLULAR-CARCINOMA; EXPRESSION; LNCRNA; PROLIFERATION; PROGRESSION; PROGNOSIS; INTERACTS; ROLES; WNT7A; endometrial adenocarcinoma; long non-coding RNA; DSCAM-AS1; transcriptome
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Frauenheilkunde und Geburtshilfe (Schwerpunkt Frauenheilkunde)
Medicine > Lehrstuhl für Innere Medizin I
Medicine > Lehrstuhl für Pathologie
Depositing User: Dr. Gernot Deinzer
Date Deposited: 14 Nov 2023 13:08
Last Modified: 14 Nov 2023 13:08
URI: https://pred.uni-regensburg.de/id/eprint/56748

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