DSCAM-AS1 Long Non-Coding RNA Exerts Oncogenic Functions in Endometrial Adenocarcinoma via Activation of a Tumor-Promoting Transcriptome Profile
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 adenocarci...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-07-01
|
| Series: | Biomedicines |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2227-9059/10/7/1727 |
| _version_ | 1797433809416749056 |
|---|---|
| author | Oliver Treeck Florian Weber Juergen Fritsch Maciej Skrzypczak Susanne Schüler-Toprak Christa Buechler Olaf Ortmann |
| author_facet | Oliver Treeck Florian Weber Juergen Fritsch Maciej Skrzypczak Susanne Schüler-Toprak Christa Buechler Olaf Ortmann |
| author_sort | Oliver Treeck |
| collection | DOAJ |
| description | 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) (<i>p</i> < 0.01) and a significant association with shorter overall survival of EC patients (HR = 1.78, <i>p</i> < 0.01). In EC, DSCAM-AS1 was associated with endometrial tumor promotor gene <i>PRL</i> and with expression of ERα and its target genes <i>TFF1</i> and <i>PGR</i>. 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 <i>NOTCH1, PTK2</i> and <i>EGR1</i>. 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. |
| first_indexed | 2024-03-09T10:22:04Z |
| format | Article |
| id | doaj.art-371de88cfdc44447a40ab0b5debc609b |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-09T10:22:04Z |
| publishDate | 2022-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-371de88cfdc44447a40ab0b5debc609b2023-12-01T21:56:26ZengMDPI AGBiomedicines2227-90592022-07-01107172710.3390/biomedicines10071727DSCAM-AS1 Long Non-Coding RNA Exerts Oncogenic Functions in Endometrial Adenocarcinoma via Activation of a Tumor-Promoting Transcriptome ProfileOliver Treeck0Florian Weber1Juergen Fritsch2Maciej Skrzypczak3Susanne Schüler-Toprak4Christa Buechler5Olaf Ortmann6Department of Gynecology and Obstetrics, University Medical Center Regensburg, 93053 Regensburg, GermanyDepartment of Pathology, University Medical Center Regensburg, 93053 Regensburg, GermanyDepartment of Infection Prevention and Infectious Diseases, University Medical Center Regensburg, 93053 Regensburg, GermanySecond Department of Gynecology, Medical University of Lublin, 20-090 Lublin, PolandDepartment of Gynecology and Obstetrics, University Medical Center Regensburg, 93053 Regensburg, GermanyDepartment of Internal Medicine I, University Medical Center Regensburg, 93053 Regensburg, GermanyDepartment of Gynecology and Obstetrics, University Medical Center Regensburg, 93053 Regensburg, GermanyAccumulating 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) (<i>p</i> < 0.01) and a significant association with shorter overall survival of EC patients (HR = 1.78, <i>p</i> < 0.01). In EC, DSCAM-AS1 was associated with endometrial tumor promotor gene <i>PRL</i> and with expression of ERα and its target genes <i>TFF1</i> and <i>PGR</i>. 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 <i>NOTCH1, PTK2</i> and <i>EGR1</i>. 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.https://www.mdpi.com/2227-9059/10/7/1727endometrial adenocarcinomalong non-coding RNADSCAM-AS1transcriptome |
| spellingShingle | Oliver Treeck Florian Weber Juergen Fritsch Maciej Skrzypczak Susanne Schüler-Toprak Christa Buechler Olaf Ortmann DSCAM-AS1 Long Non-Coding RNA Exerts Oncogenic Functions in Endometrial Adenocarcinoma via Activation of a Tumor-Promoting Transcriptome Profile Biomedicines endometrial adenocarcinoma long non-coding RNA DSCAM-AS1 transcriptome |
| title | DSCAM-AS1 Long Non-Coding RNA Exerts Oncogenic Functions in Endometrial Adenocarcinoma via Activation of a Tumor-Promoting Transcriptome Profile |
| title_full | DSCAM-AS1 Long Non-Coding RNA Exerts Oncogenic Functions in Endometrial Adenocarcinoma via Activation of a Tumor-Promoting Transcriptome Profile |
| title_fullStr | DSCAM-AS1 Long Non-Coding RNA Exerts Oncogenic Functions in Endometrial Adenocarcinoma via Activation of a Tumor-Promoting Transcriptome Profile |
| title_full_unstemmed | DSCAM-AS1 Long Non-Coding RNA Exerts Oncogenic Functions in Endometrial Adenocarcinoma via Activation of a Tumor-Promoting Transcriptome Profile |
| title_short | DSCAM-AS1 Long Non-Coding RNA Exerts Oncogenic Functions in Endometrial Adenocarcinoma via Activation of a Tumor-Promoting Transcriptome Profile |
| title_sort | dscam as1 long non coding rna exerts oncogenic functions in endometrial adenocarcinoma via activation of a tumor promoting transcriptome profile |
| topic | endometrial adenocarcinoma long non-coding RNA DSCAM-AS1 transcriptome |
| url | https://www.mdpi.com/2227-9059/10/7/1727 |
| work_keys_str_mv | AT olivertreeck dscamas1longnoncodingrnaexertsoncogenicfunctionsinendometrialadenocarcinomaviaactivationofatumorpromotingtranscriptomeprofile AT florianweber dscamas1longnoncodingrnaexertsoncogenicfunctionsinendometrialadenocarcinomaviaactivationofatumorpromotingtranscriptomeprofile AT juergenfritsch dscamas1longnoncodingrnaexertsoncogenicfunctionsinendometrialadenocarcinomaviaactivationofatumorpromotingtranscriptomeprofile AT maciejskrzypczak dscamas1longnoncodingrnaexertsoncogenicfunctionsinendometrialadenocarcinomaviaactivationofatumorpromotingtranscriptomeprofile AT susanneschulertoprak dscamas1longnoncodingrnaexertsoncogenicfunctionsinendometrialadenocarcinomaviaactivationofatumorpromotingtranscriptomeprofile AT christabuechler dscamas1longnoncodingrnaexertsoncogenicfunctionsinendometrialadenocarcinomaviaactivationofatumorpromotingtranscriptomeprofile AT olafortmann dscamas1longnoncodingrnaexertsoncogenicfunctionsinendometrialadenocarcinomaviaactivationofatumorpromotingtranscriptomeprofile |