Regulation of microRNA biosynthesis and expression in 2102Ep embryonal carcinoma stem cells is mirrored in ovarian serous adenocarcinoma patients
<p>Abstract</p> <p>Background</p> <p>Tumours with high proportions of differentiated cells are considered to be of a lower grade to those containing high proportions of undifferentiated cells. This property may be linked to the differentiation properties of stem cell-li...
| Main Authors: | , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2009-12-01
|
| Series: | Journal of Ovarian Research |
| Online Access: | http://www.ovarianresearch.com/content/2/1/19 |
| _version_ | 1797964480494174208 |
|---|---|
| author | Gallagher Michael F Flavin Richard J Elbaruni Salah A McInerney Jamie K Smyth Paul C Salley Yvonne M Vencken Sebastian F O'Toole Sharon A Laios Alexandros Lee Mathia YC Denning Karen Li Jinghuan Aherne Sinead T Lao Kai Q Martin Cara M Sheils Orla M O'Leary John J |
| author_facet | Gallagher Michael F Flavin Richard J Elbaruni Salah A McInerney Jamie K Smyth Paul C Salley Yvonne M Vencken Sebastian F O'Toole Sharon A Laios Alexandros Lee Mathia YC Denning Karen Li Jinghuan Aherne Sinead T Lao Kai Q Martin Cara M Sheils Orla M O'Leary John J |
| author_sort | Gallagher Michael F |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Tumours with high proportions of differentiated cells are considered to be of a lower grade to those containing high proportions of undifferentiated cells. This property may be linked to the differentiation properties of stem cell-like populations within malignancies. We aim to identify molecular mechanism associated with the generation of tumours with differing grades from malignant stem cell populations with different differentiation potentials. In this study we assessed microRNA (miRNA) regulation in two populations of malignant Embryonal Carcinoma (EC) stem cell, which differentiate (NTera2) or remain undifferentiated (2102Ep) during tumourigenesis, and compared this to miRNA regulation in ovarian serous carcinoma (OSC) patient samples.</p> <p>Methods</p> <p>miRNA expression was assessed in NTera2 and 2102Ep cells in the undifferentiated and differentiated states and compared to that of OSC samples using miRNA qPCR.</p> <p>Results</p> <p>Our analysis reveals a substantial overlap between miRNA regulation in 2102Ep cells and OSC samples in terms of miRNA biosynthesis and expression of mature miRNAs, particularly those of the miR-17/92 family and clustering to chromosomes 14 and 19. In the undifferentiated state 2102Ep cells expressed mature miRNAs at up to 15,000 fold increased levels despite decreased expression of miRNA biosynthesis genes Drosha and Dicer. 2102Ep cells avoid differentiation, which we show is associated with consistent levels of expression of miRNA biosynthesis genes and mature miRNAs while expression of miRNAs clustering to chromosomes 14 and 19 is deemphasised. OSC patient samples displayed decreased expression of miRNA biosynthesis genes, decreased expression of mature miRNAs and prominent clustering to chromosome 14 but not 19. This indicates that miRNA biosynthesis and levels of miRNA expression, particularly from chromosome 14, are tightly regulated both in progenitor cells and in tumour samples.</p> <p>Conclusion</p> <p>miRNA biosynthesis and expression of mature miRNAs, particularly the miR-17/92 family and those clustering to chromosomes 14 and 19, are highly regulated in both progenitor cells and tumour samples. Strikingly, 2102Ep cells are not simply malfunctioning but respond to differentiation specifically, a mechanism that is highly relevant to OSC samples. Our identification and future manipulation of these miRNAs may facilitate generation of lower grade malignancies from these high-grade cells.</p> |
| first_indexed | 2024-04-11T01:45:43Z |
| format | Article |
| id | doaj.art-94d9c4f9b4a74aa886b21e5182b624fd |
| institution | Directory Open Access Journal |
| issn | 1757-2215 |
| language | English |
| last_indexed | 2024-04-11T01:45:43Z |
| publishDate | 2009-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Ovarian Research |
| spelling | doaj.art-94d9c4f9b4a74aa886b21e5182b624fd2023-01-03T07:55:33ZengBMCJournal of Ovarian Research1757-22152009-12-01211910.1186/1757-2215-2-19Regulation of microRNA biosynthesis and expression in 2102Ep embryonal carcinoma stem cells is mirrored in ovarian serous adenocarcinoma patientsGallagher Michael FFlavin Richard JElbaruni Salah AMcInerney Jamie KSmyth Paul CSalley Yvonne MVencken Sebastian FO'Toole Sharon ALaios AlexandrosLee Mathia YCDenning KarenLi JinghuanAherne Sinead TLao Kai QMartin Cara MSheils Orla MO'Leary John J<p>Abstract</p> <p>Background</p> <p>Tumours with high proportions of differentiated cells are considered to be of a lower grade to those containing high proportions of undifferentiated cells. This property may be linked to the differentiation properties of stem cell-like populations within malignancies. We aim to identify molecular mechanism associated with the generation of tumours with differing grades from malignant stem cell populations with different differentiation potentials. In this study we assessed microRNA (miRNA) regulation in two populations of malignant Embryonal Carcinoma (EC) stem cell, which differentiate (NTera2) or remain undifferentiated (2102Ep) during tumourigenesis, and compared this to miRNA regulation in ovarian serous carcinoma (OSC) patient samples.</p> <p>Methods</p> <p>miRNA expression was assessed in NTera2 and 2102Ep cells in the undifferentiated and differentiated states and compared to that of OSC samples using miRNA qPCR.</p> <p>Results</p> <p>Our analysis reveals a substantial overlap between miRNA regulation in 2102Ep cells and OSC samples in terms of miRNA biosynthesis and expression of mature miRNAs, particularly those of the miR-17/92 family and clustering to chromosomes 14 and 19. In the undifferentiated state 2102Ep cells expressed mature miRNAs at up to 15,000 fold increased levels despite decreased expression of miRNA biosynthesis genes Drosha and Dicer. 2102Ep cells avoid differentiation, which we show is associated with consistent levels of expression of miRNA biosynthesis genes and mature miRNAs while expression of miRNAs clustering to chromosomes 14 and 19 is deemphasised. OSC patient samples displayed decreased expression of miRNA biosynthesis genes, decreased expression of mature miRNAs and prominent clustering to chromosome 14 but not 19. This indicates that miRNA biosynthesis and levels of miRNA expression, particularly from chromosome 14, are tightly regulated both in progenitor cells and in tumour samples.</p> <p>Conclusion</p> <p>miRNA biosynthesis and expression of mature miRNAs, particularly the miR-17/92 family and those clustering to chromosomes 14 and 19, are highly regulated in both progenitor cells and tumour samples. Strikingly, 2102Ep cells are not simply malfunctioning but respond to differentiation specifically, a mechanism that is highly relevant to OSC samples. Our identification and future manipulation of these miRNAs may facilitate generation of lower grade malignancies from these high-grade cells.</p>http://www.ovarianresearch.com/content/2/1/19 |
| spellingShingle | Gallagher Michael F Flavin Richard J Elbaruni Salah A McInerney Jamie K Smyth Paul C Salley Yvonne M Vencken Sebastian F O'Toole Sharon A Laios Alexandros Lee Mathia YC Denning Karen Li Jinghuan Aherne Sinead T Lao Kai Q Martin Cara M Sheils Orla M O'Leary John J Regulation of microRNA biosynthesis and expression in 2102Ep embryonal carcinoma stem cells is mirrored in ovarian serous adenocarcinoma patients Journal of Ovarian Research |
| title | Regulation of microRNA biosynthesis and expression in 2102Ep embryonal carcinoma stem cells is mirrored in ovarian serous adenocarcinoma patients |
| title_full | Regulation of microRNA biosynthesis and expression in 2102Ep embryonal carcinoma stem cells is mirrored in ovarian serous adenocarcinoma patients |
| title_fullStr | Regulation of microRNA biosynthesis and expression in 2102Ep embryonal carcinoma stem cells is mirrored in ovarian serous adenocarcinoma patients |
| title_full_unstemmed | Regulation of microRNA biosynthesis and expression in 2102Ep embryonal carcinoma stem cells is mirrored in ovarian serous adenocarcinoma patients |
| title_short | Regulation of microRNA biosynthesis and expression in 2102Ep embryonal carcinoma stem cells is mirrored in ovarian serous adenocarcinoma patients |
| title_sort | regulation of microrna biosynthesis and expression in 2102ep embryonal carcinoma stem cells is mirrored in ovarian serous adenocarcinoma patients |
| url | http://www.ovarianresearch.com/content/2/1/19 |
| work_keys_str_mv | AT gallaghermichaelf regulationofmicrornabiosynthesisandexpressionin2102epembryonalcarcinomastemcellsismirroredinovarianserousadenocarcinomapatients AT flavinrichardj regulationofmicrornabiosynthesisandexpressionin2102epembryonalcarcinomastemcellsismirroredinovarianserousadenocarcinomapatients AT elbarunisalaha regulationofmicrornabiosynthesisandexpressionin2102epembryonalcarcinomastemcellsismirroredinovarianserousadenocarcinomapatients AT mcinerneyjamiek regulationofmicrornabiosynthesisandexpressionin2102epembryonalcarcinomastemcellsismirroredinovarianserousadenocarcinomapatients AT smythpaulc regulationofmicrornabiosynthesisandexpressionin2102epembryonalcarcinomastemcellsismirroredinovarianserousadenocarcinomapatients AT salleyyvonnem regulationofmicrornabiosynthesisandexpressionin2102epembryonalcarcinomastemcellsismirroredinovarianserousadenocarcinomapatients AT venckensebastianf regulationofmicrornabiosynthesisandexpressionin2102epembryonalcarcinomastemcellsismirroredinovarianserousadenocarcinomapatients AT otoolesharona regulationofmicrornabiosynthesisandexpressionin2102epembryonalcarcinomastemcellsismirroredinovarianserousadenocarcinomapatients AT laiosalexandros regulationofmicrornabiosynthesisandexpressionin2102epembryonalcarcinomastemcellsismirroredinovarianserousadenocarcinomapatients AT leemathiayc regulationofmicrornabiosynthesisandexpressionin2102epembryonalcarcinomastemcellsismirroredinovarianserousadenocarcinomapatients AT denningkaren regulationofmicrornabiosynthesisandexpressionin2102epembryonalcarcinomastemcellsismirroredinovarianserousadenocarcinomapatients AT lijinghuan regulationofmicrornabiosynthesisandexpressionin2102epembryonalcarcinomastemcellsismirroredinovarianserousadenocarcinomapatients AT ahernesineadt regulationofmicrornabiosynthesisandexpressionin2102epembryonalcarcinomastemcellsismirroredinovarianserousadenocarcinomapatients AT laokaiq regulationofmicrornabiosynthesisandexpressionin2102epembryonalcarcinomastemcellsismirroredinovarianserousadenocarcinomapatients AT martincaram regulationofmicrornabiosynthesisandexpressionin2102epembryonalcarcinomastemcellsismirroredinovarianserousadenocarcinomapatients AT sheilsorlam regulationofmicrornabiosynthesisandexpressionin2102epembryonalcarcinomastemcellsismirroredinovarianserousadenocarcinomapatients AT olearyjohnj regulationofmicrornabiosynthesisandexpressionin2102epembryonalcarcinomastemcellsismirroredinovarianserousadenocarcinomapatients |