Targeting Glioma Stem Cells by Functional Inhibition of a Prosurvival OncomiR-138 in Malignant Gliomas
Malignant gliomas are the most aggressive forms of brain tumors, associated with high rates of morbidity and mortality. Recurrence and tumorigenesis are attributed to a subpopulation of tumor-initiating glioma stem cells (GSCs) that are intrinsically resistant to therapy. Initiation and progression...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2012-09-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124712002227 |
| _version_ | 1818141118806622208 |
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| author | Xin Hui Derryn Chan Srikanth Nama Felicia Gopal Pamela Rizk Srinivas Ramasamy Gopinath Sundaram Ghim Siong Ow Ivshina Anna Vladimirovna Vivek Tanavde Johannes Haybaeck Vladimir Kuznetsov Prabha Sampath |
| author_facet | Xin Hui Derryn Chan Srikanth Nama Felicia Gopal Pamela Rizk Srinivas Ramasamy Gopinath Sundaram Ghim Siong Ow Ivshina Anna Vladimirovna Vivek Tanavde Johannes Haybaeck Vladimir Kuznetsov Prabha Sampath |
| author_sort | Xin Hui Derryn Chan |
| collection | DOAJ |
| description | Malignant gliomas are the most aggressive forms of brain tumors, associated with high rates of morbidity and mortality. Recurrence and tumorigenesis are attributed to a subpopulation of tumor-initiating glioma stem cells (GSCs) that are intrinsically resistant to therapy. Initiation and progression of gliomas have been linked to alterations in microRNA expression. Here, we report the identification of microRNA-138 (miR-138) as a molecular signature of GSCs and demonstrate a vital role for miR-138 in promoting growth and survival of bona fide tumor-initiating cells with self-renewal potential. Sequence-specific functional inhibition of miR-138 prevents tumorsphere formation in vitro and impedes tumorigenesis in vivo. We delineate the components of the miR-138 regulatory network by loss-of-function analysis to identify specific regulators of apoptosis. Finally, the higher expression of miR-138 in GSCs compared to non-neoplastic tissue and association with tumor recurrence and survival highlights the clinical significance of miR-138 as a prognostic biomarker and a therapeutic target for treatment of malignant gliomas. |
| first_indexed | 2024-12-11T10:54:48Z |
| format | Article |
| id | doaj.art-33bc9d05229e435b9f03d3d7daec91c4 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-11T10:54:48Z |
| publishDate | 2012-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-33bc9d05229e435b9f03d3d7daec91c42022-12-22T01:10:09ZengElsevierCell Reports2211-12472012-09-012359160210.1016/j.celrep.2012.07.012Targeting Glioma Stem Cells by Functional Inhibition of a Prosurvival OncomiR-138 in Malignant GliomasXin Hui Derryn Chan0Srikanth Nama1Felicia Gopal2Pamela Rizk3Srinivas Ramasamy4Gopinath Sundaram5Ghim Siong Ow6Ivshina Anna Vladimirovna7Vivek Tanavde8Johannes Haybaeck9Vladimir Kuznetsov10Prabha Sampath11Institute of Medical Biology, Agency for Science Technology and Research, Singapore 138648, SingaporeInstitute of Medical Biology, Agency for Science Technology and Research, Singapore 138648, SingaporeInstitute of Medical Biology, Agency for Science Technology and Research, Singapore 138648, SingaporeInstitute of Medical Biology, Agency for Science Technology and Research, Singapore 138648, SingaporeInstitute of Medical Biology, Agency for Science Technology and Research, Singapore 138648, SingaporeInstitute of Medical Biology, Agency for Science Technology and Research, Singapore 138648, SingaporeBioinformatics Institute, Agency for Science Technology and Research, Singapore 138671, SingaporeBioinformatics Institute, Agency for Science Technology and Research, Singapore 138671, SingaporeBioinformatics Institute, Agency for Science Technology and Research, Singapore 138671, SingaporeDepartment of Neuropathology, Medical University of Graz, 8036 Graz, AustriaBioinformatics Institute, Agency for Science Technology and Research, Singapore 138671, SingaporeInstitute of Medical Biology, Agency for Science Technology and Research, Singapore 138648, SingaporeMalignant gliomas are the most aggressive forms of brain tumors, associated with high rates of morbidity and mortality. Recurrence and tumorigenesis are attributed to a subpopulation of tumor-initiating glioma stem cells (GSCs) that are intrinsically resistant to therapy. Initiation and progression of gliomas have been linked to alterations in microRNA expression. Here, we report the identification of microRNA-138 (miR-138) as a molecular signature of GSCs and demonstrate a vital role for miR-138 in promoting growth and survival of bona fide tumor-initiating cells with self-renewal potential. Sequence-specific functional inhibition of miR-138 prevents tumorsphere formation in vitro and impedes tumorigenesis in vivo. We delineate the components of the miR-138 regulatory network by loss-of-function analysis to identify specific regulators of apoptosis. Finally, the higher expression of miR-138 in GSCs compared to non-neoplastic tissue and association with tumor recurrence and survival highlights the clinical significance of miR-138 as a prognostic biomarker and a therapeutic target for treatment of malignant gliomas.http://www.sciencedirect.com/science/article/pii/S2211124712002227 |
| spellingShingle | Xin Hui Derryn Chan Srikanth Nama Felicia Gopal Pamela Rizk Srinivas Ramasamy Gopinath Sundaram Ghim Siong Ow Ivshina Anna Vladimirovna Vivek Tanavde Johannes Haybaeck Vladimir Kuznetsov Prabha Sampath Targeting Glioma Stem Cells by Functional Inhibition of a Prosurvival OncomiR-138 in Malignant Gliomas Cell Reports |
| title | Targeting Glioma Stem Cells by Functional Inhibition of a Prosurvival OncomiR-138 in Malignant Gliomas |
| title_full | Targeting Glioma Stem Cells by Functional Inhibition of a Prosurvival OncomiR-138 in Malignant Gliomas |
| title_fullStr | Targeting Glioma Stem Cells by Functional Inhibition of a Prosurvival OncomiR-138 in Malignant Gliomas |
| title_full_unstemmed | Targeting Glioma Stem Cells by Functional Inhibition of a Prosurvival OncomiR-138 in Malignant Gliomas |
| title_short | Targeting Glioma Stem Cells by Functional Inhibition of a Prosurvival OncomiR-138 in Malignant Gliomas |
| title_sort | targeting glioma stem cells by functional inhibition of a prosurvival oncomir 138 in malignant gliomas |
| url | http://www.sciencedirect.com/science/article/pii/S2211124712002227 |
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