Journal
NEURO-ONCOLOGY
Volume 21, Issue 6, Pages 742-754Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/neuonc/noz038
Keywords
chromatin conformation remodeling; glioma; malignance; prognostic biomarker; SND1
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Funding
- National Natural Science Foundation of China [81672592, 81502166, 81872061]
- Program of Science and Technology of Tianjin Municipality [16JCQNJC13400, 17JCYBJC27100]
- Program of Tianjin Municipal Health Bureau [15KJ147]
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Background Upregulation of staphylococcal nuclease domain-containing protein 1 (SND1) is a common phenomenon in different human malignant tissues. However, little information is available on the underlying mechanisms through which SND1 affects glioma cell proliferation and invasion. Methods SND1, Ras homolog family member A (RhoA), and marker of proliferation Ki-67 (MKI67) were analyzed in 187 gliomas by immunostaining. The correlation between those markers and patients' prognoses was assessed using the Kaplan-Meier estimator. Gene Ontology, chromatin immunoprecipitation, electrophoretic mobility shift assay, and chromosome conformation capture were applied to identify SND1-activated target genes. We also used MTT, colony formation, transwell and orthotopic implantation assays to investigate SND1 function in glioma cell proliferative and invasive activity. Results We identified SND1 and RhoA as independent predictors of poor prognosis in glioma patients. SND1 knockdown significantly suppressed the proliferation and invasion of glioma cells. Mechanistically, we discovered that SND1 facilitated malignant glioma phenotypes by epigenetically inducing chromatin topological interaction, which activated downstream RhoA transcription. RhoA sequentially regulated expression of CCND1, CCNE1, CDK4, and CDKN1B and accelerated G1/S phase transition in glioma cell proliferation. Conclusions Our findings identify SND1 as a novel chromatin architectural modifier and promising prognostic indicator for glioma classification and treatment.
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