The novel chromatin architectural regulator SND1 promotes glioma proliferation and invasion and predicts the prognosis of patients

Abstract

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. Key Points 1. SND1 is an independent predictor for golima prognosis. 2. SND1 is a novel chromatin architectural modifier and facilitates proliferation, migration and invasion of glioma cells. Glioma has the highest incidence among primary brain tumors. 1 The high-grade malignant glioblastoma (GBM) is easy to relapse and is lethal. Due to the diverse intragroup survival, variations exist among individual patients, 2,3 current glioma histopathology diagnostic criteria has deficiency on comprehensive evaluation of glioma prognosis. 4 Therefore, exploring

Splicing Machinery is Dysregulated in Pituitary Neuroendocrine Tumors and is Associated with Aggressiveness Features

“…Nonetheless, the clear alteration of these spliceosome components found in our global cohort of NFPTs has also been observed in other tumor pathologies. Specifically, SRSF9 and SND1 have been found overexpressed in several tumor pathologies, such as breast cancer, bladder cancer, glioblastoma, melanoma, or hepatocellular carcinoma, where they have been associated with an increase in cell proliferation, invasion and poor prognosis [47,48,49,50,51]. The fact that these SFs were downregulated in NFPTs, in contrast with the overexpression observed in other pathologies, may be likely reflect the complexity, heterogeneity, and limited functional deployment of these tumors.…”

<p>LncRNA LINC00665 Promotes Prostate Cancer Progression via miR-1224-5p/SND1 Axis</p>

“…A recent study reported that SND1 overexpression promotes growth and metastasis of glioma cells. 35 Besides, other works also indicated that SND1 upregulation contributes to tumorigenesis, such as osteosarcoma, hepatocellular carcinoma and breast cancer. [36][37][38] Our data indicated that SND1 expression was upregulated in PC tissues.…”

The diagnostic and prognostic role of RhoA in hepatocellular carcinoma

“…Breast cancer samples with phosphorylated RhoA (P-RhoA) were associated with poorer prognosis [27]. Lin Yu demonstrated that SND1 (Staphylococcal nuclease domain-containing protein 1) and RhoA were independent predictors of poor prognosis in glioma patients [28]. Our results suggested only a relationship between gender and RhoA gene expression.…”