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m6A RNA Methylation Regulates the Self-Renewal and Tumorigenesis of Glioblastoma Stem Cells
Open accessAbstract
RNA modifications play critical roles in important biological processes. However, the functions of N 6 -methyladenosine (m 6 A) mRNA modification in cancer biology and cancer stem cells remain largely unknown. Here, we show that m 6 A mRNA modification is critical for glioblastoma stem cell (GSC) self-renewal and tumorigenesis. Knockdown of METTL3 or METTL14, key components of the RNA methyltransferase complex, dramatically promotes human GSC growth, self-renewal, and tumorigenesis. In contrast, overexpression of METTL3 or inhibition of the RNA demethylase FTO suppresses GSC growth and self-renewal. Moreover, inhibition of FTO suppresses tumor progression and prolongs lifespan of GSC-grafted mice substantially. m 6 A sequencing reveals that knockdown of METTL3 or METTL14 induced changes in mRNA m 6 A enrichment and altered mRNA expression of genes (e.g., ADAM19 ) with critical biological functions in GSCs. In summary, this study identifies the m 6 A mRNA methylation machinery as promising therapeutic targets for glioblastoma.
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Metadata
- Authors
- Cui, Q., Shi, H., Ye, P., Li, L., Qu, Q., Sun, G., Sun, G., Lu, Z., Huang, Y., Yang, C.-G., Riggs, A. D., He, C., & Shi, Y.
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2017-03
- Volume
- 18
- Issue
- 11
- Pages
- 2622-2634
- ISSN
- 2211-1247 (ISSN-L)
- OpenAlex
- W2600862208
- Cited by
- 1,252
- References
- 57
- FWCI
- 40.18
- Type
- journal article
- Language
- en
- Open access
- gold
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