Article: Loss of brain-enriched miR-124 microRNA enhances stem-like traits and invasiveness of glioma cells
| Title | Loss of brain-enriched miR-124 microRNA enhances stem-like traits and invasiveness of glioma cells | ||||||
|---|---|---|---|---|---|---|---|
| Authors | Xia, H1 2 5 Cheung, WKC1 4 Ng, SS1 Jiang, X2 Jiang, S2 Sze, J1 5 Leung, GKK1 Lu, G5 Chan, DTM5 Bian, XW3 Kung, HF3 5 Poon, WS5 Lin, MC1 3 5 | ||||||
| Issue Date | 2012 | ||||||
| Publisher | American Society for Biochemistry and Molecular Biology, Inc. The Journal's web site is located at http://www.jbc.org/ | ||||||
| Citation | Journal Of Biological Chemistry, 2012, v. 287 n. 13, p. 9962-9971 [How to Cite?] DOI: http://dx.doi.org/10.1074/jbc.M111.332627 | ||||||
| Abstract | miR-124 is a brain-enriched microRNA that plays a crucial role in neural development and has been shown to be down-regulated in glioma and medulloblastoma, suggesting its possible involvement in brain tumor progression. Here, we show that miR-124 is down-regulated in a panel of different grades of glioma tissues and in all of the human glioma cell lines we examined. By integrated bioinformatics analysis and experimental confirmation, we identified SNAI2, which is often up-regulated in glioma, as a direct functional target of miR-124. Because SNAI2 has been shown to regulate stem cell functions, we examined the roles of miR-124 and SNAI2 in glioma cell stem-like traits. The results showed that overexpression of miR-124 and knockdown of SNAI2 reduced neurosphere formation, CD133 + cell subpopulation, and stem cell marker (BMI1, Nanog, and Nestin) expression, and these effects could be rescued by re-expression of SNAI2. Furthermore, enhanced miR-124 expression significantly inhibited glioma cell invasion in vitro. Finally, stable overexpression of miR-124 and knockdown of SNAI2 inhibited the tumorigenicity and invasion of glioma cells in vivo. These findings reveal, for the first time, that the tumor suppressor activity of miR-124 could be partly due to its inhibitory effects on glioma stem-like traits and invasiveness through SNAI2. © 2012 by The American Society for Biochemistry and Molecular Biology, Inc. | ||||||
| ISSN | 0021-9258 2011 Impact Factor: 4.773 2011 SCImago Journal Rankings: 0.793 | ||||||
| DOI | http://dx.doi.org/10.1074/jbc.M111.332627 | ||||||
| ISI Accession Number ID | WOS:000302167200028
Funding Information: This work was supported by Grants 467109 and 470911 from the Research Grants Council of the Hong Kong Special Administrative Region, China, and by Grants 2010CB529400 and 2010CB912800 from the National Basic Research Program of China (973 Program). | ||||||
| PubMed Central ID | PMC3322968 | ||||||
| References | References in Scopus |
| dc.contributor.author | Xia, H | ||||||
|---|---|---|---|---|---|---|---|
| dc.contributor.author | Cheung, WKC | ||||||
| dc.contributor.author | Ng, SS | ||||||
| dc.contributor.author | Jiang, X | ||||||
| dc.contributor.author | Jiang, S | ||||||
| dc.contributor.author | Sze, J | ||||||
| dc.contributor.author | Leung, GKK | ||||||
| dc.contributor.author | Lu, G | ||||||
| dc.contributor.author | Chan, DTM | ||||||
| dc.contributor.author | Bian, XW | ||||||
| dc.contributor.author | Kung, HF | ||||||
| dc.contributor.author | Poon, WS | ||||||
| dc.contributor.author | Lin, MC | ||||||
| dc.date.accessioned | 2012-04-24T07:53:12Z | ||||||
| dc.date.available | 2012-04-24T07:53:12Z | ||||||
| dc.date.issued | 2012 | ||||||
| dc.description.abstract | miR-124 is a brain-enriched microRNA that plays a crucial role in neural development and has been shown to be down-regulated in glioma and medulloblastoma, suggesting its possible involvement in brain tumor progression. Here, we show that miR-124 is down-regulated in a panel of different grades of glioma tissues and in all of the human glioma cell lines we examined. By integrated bioinformatics analysis and experimental confirmation, we identified SNAI2, which is often up-regulated in glioma, as a direct functional target of miR-124. Because SNAI2 has been shown to regulate stem cell functions, we examined the roles of miR-124 and SNAI2 in glioma cell stem-like traits. The results showed that overexpression of miR-124 and knockdown of SNAI2 reduced neurosphere formation, CD133 + cell subpopulation, and stem cell marker (BMI1, Nanog, and Nestin) expression, and these effects could be rescued by re-expression of SNAI2. Furthermore, enhanced miR-124 expression significantly inhibited glioma cell invasion in vitro. Finally, stable overexpression of miR-124 and knockdown of SNAI2 inhibited the tumorigenicity and invasion of glioma cells in vivo. These findings reveal, for the first time, that the tumor suppressor activity of miR-124 could be partly due to its inhibitory effects on glioma stem-like traits and invasiveness through SNAI2. © 2012 by The American Society for Biochemistry and Molecular Biology, Inc. | ||||||
| dc.description.nature | Link_to_subscribed_fulltext | ||||||
| dc.identifier.citation | Journal Of Biological Chemistry, 2012, v. 287 n. 13, p. 9962-9971 [How to Cite?] DOI: http://dx.doi.org/10.1074/jbc.M111.332627 | ||||||
| dc.identifier.doi | http://dx.doi.org/10.1074/jbc.M111.332627 | ||||||
| dc.identifier.epage | 9971 | ||||||
| dc.identifier.hkuros | 199190 | ||||||
| dc.identifier.isi | WOS:000302167200028
Funding Information: This work was supported by Grants 467109 and 470911 from the Research Grants Council of the Hong Kong Special Administrative Region, China, and by Grants 2010CB529400 and 2010CB912800 from the National Basic Research Program of China (973 Program). | ||||||
| dc.identifier.issn | 0021-9258 2011 Impact Factor: 4.773 2011 SCImago Journal Rankings: 0.793 | ||||||
| dc.identifier.issue | 13 | ||||||
| dc.identifier.pmcid | PMC3322968 | ||||||
| dc.identifier.pmid | 22253443 | ||||||
| dc.identifier.scopus | eid_2-s2.0-84858992906 | ||||||
| dc.identifier.spage | 9962 | ||||||
| dc.identifier.uri | http://hdl.handle.net/10722/146425 | ||||||
| dc.identifier.volume | 287 | ||||||
| dc.language | eng | ||||||
| dc.publisher | American Society for Biochemistry and Molecular Biology, Inc. The Journal's web site is located at http://www.jbc.org/ | ||||||
| dc.publisher.place | United States | ||||||
| dc.relation.ispartof | Journal of Biological Chemistry | ||||||
| dc.relation.references | References in Scopus | ||||||
| dc.rights | Journal of Biological Chemistry. Copyright © American Society for Biochemistry and Molecular Biology, Inc. | ||||||
| dc.subject.mesh | Antigens, Differentiation - genetics - metabolism | ||||||
| dc.subject.mesh | Gene Expression Regulation, Neoplastic | ||||||
| dc.subject.mesh | Genes, Tumor Suppressor | ||||||
| dc.subject.mesh | Glioma - genetics - metabolism - pathology | ||||||
| dc.subject.mesh | MicroRNAs - biosynthesis - genetics | ||||||
| dc.title | Loss of brain-enriched miR-124 microRNA enhances stem-like traits and invasiveness of glioma cells | ||||||
| dc.type | Article |
Author Affiliations
- The University of Hong Kong
- Sun Yat-Sen University
- Southwestern Hospital Chongqing
- Yale University School of Medicine
- Chinese University of Hong Kong