DSCAM-AS1 Long Non-Coding RNA Exerts Oncogenic Functions in Endometrial Adenocarcinoma via Activation of a
Oliver Treeck1, Florian Weber2, Juergen Fritsch3
1Department of Gynecology and Obstetrics, University Medical Center Regensburg, 93053 Regensburg, Germany.
Biomedicines
|July 27, 2022
Summary
Long non-coding RNA DSCAM-AS1 promotes endometrial cancer (EC) by activating oncogenic gene expression. Silencing DSCAM-AS1 inhibits EC cell growth and triggers anti-tumoral gene networks, suggesting its potential as a therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Long non-coding RNA DSCAM-AS1 is implicated as a tumor promoter in various cancers.
- DSCAM-AS1 is notably responsive to estrogen receptor alpha (ERα) induction in breast cancer.
- Its role in endometrial adenocarcinoma (EC) requires further investigation.
Purpose of the Study:
- To investigate the function of DSCAM-AS1 in endometrial adenocarcinoma.
- To analyze the association of DSCAM-AS1 with clinical outcomes and molecular markers in EC.
- To elucidate the molecular mechanisms underlying DSCAM-AS1's role in EC progression.
Main Methods:
- In silico analysis of open-source data for DSCAM-AS1 expression and patient survival.
- In vitro studies involving RNA interference (RNAi) to silence DSCAM-AS1 in EC cell lines.
- Affymetrix microarray analysis to assess transcriptome-wide changes upon DSCAM-AS1 knockdown.
Main Results:
- DSCAM-AS1 was overexpressed in EC tissues and associated with shorter overall survival.
- DSCAM-AS1 expression correlated with tumor promoter gene PRL, ERα, and its target genes TFF1 and PGR in EC.
- Silencing DSCAM-AS1 reduced EC cell growth and expression of proliferation activators (NOTCH1, PTK2, EGR1), particularly in ERα-negative cells.
- Microarray analysis revealed DSCAM-AS1 knockdown induced an anti-tumoral transcriptome, downregulating oncogenes and upregulating tumor suppressors.
- Genes regulated by DSCAM-AS1 silencing in vitro showed inverse correlation with DSCAM-AS1 levels in EC tissues.
Conclusions:
- DSCAM-AS1 exhibits an oncogenic function in endometrial adenocarcinoma.
- DSCAM-AS1 promotes EC by activating a tumor-promoting transcriptome profile.
- DSCAM-AS1 represents a potential therapeutic target for endometrial cancer.
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