miR-644a is a tumor cell-intrinsic mediator of sex bias in glioblastoma

Abstract Background Biological sex is an important risk factor for glioblastoma (GBM), with males having a higher incidence and poorer prognosis. The mechanisms for this sex bias are thought to be both tumor intrinsic and tumor extrinsic. MicroRNAs (miRNAs), key posttranscriptional regulators of gen...

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Bibliographic Details
Published in:Neuro-oncology advances 2024-01, Vol.6 (1), p.vdae183
Main Authors: Hong, Ellen S, Wang, Sabrina Z, Ponti, András K, Hajdari, Nicole, Lee, Juyeun, Mulkearns-Hubert, Erin E, Volovetz, Josephine, Kay, Kristen E, Lathia, Justin D, Dhawan, Andrew
Format: Article
Language:English
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Summary:Abstract Background Biological sex is an important risk factor for glioblastoma (GBM), with males having a higher incidence and poorer prognosis. The mechanisms for this sex bias are thought to be both tumor intrinsic and tumor extrinsic. MicroRNAs (miRNAs), key posttranscriptional regulators of gene expression, have been previously linked to sex differences in various cell types and diseases, but their role in the sex bias of GBM remains unknown. Methods We leveraged previously published paired miRNA and mRNA sequencing of 39 GBM patients (22 male, 17 female) to identify sex-biased miRNAs. We further interrogated a separate single-cell RNA-sequencing dataset of 110 GBM patients to examine whether differences in miRNA target gene expression were tumor cell-intrinsic or tumor cell extrinsic. Results were validated in a panel of patient-derived cell models. Results We identified 10 sex-biased miRNAs (padjusted 
ISSN:2632-2498
2632-2498
DOI:10.1093/noajnl/vdae183