Prognostic value of NUSAP1 in progression and expansion of glioblastoma multiforme

Abstract

Nucleolar and spindle-associated protein (NUSAP1) is a microtubule and chromatin-binding protein that stabilizes microtubules to prevent depolymerization, maintains spindle integrity. NUSAP1 could cross-link spindles into aster-like structures, networks and fibers. It has also been found to play roles in progression of several cancers. However, the potential correlation between NUSAP1 and clinical outcome in patients with glioblastoma multiforme (GBM) remains largely unknown. In the current study, we demonstrated that NUSAP1 was significantly up-regulated in GBM tissues compared with adult non-tumor brain tissues both in a validated cohort and a TCGA cohort. In addition, Kaplan-Meier analysis indicated that patients with high NUSAP1 expression had significantly lower OS (P = 0.0027). Additionally, in the TCGA cohort, NUSAP1 expression was relatively lower in GBM patients within the neural and mesenchymal subtypes compared to other subtypes, and associated with the status of several genetic aberrations such as PTEN deletion and wild type IDH1. The present study provides new insights and evidence that NUSAP1 over-expression was significantly correlated with progression and prognosis of GBM. Furthermore, knockdown of NUSAP1 revealed its regulation on G2/M progression and cell proliferation (both in vitro and in vivo). These data demonstrate that NUSAP1 could serve as a novel prognostic biomarker and a potential therapeutic target for GBM.

Downregulation of NUSAP1 suppresses cell proliferation, migration, and invasion via inhibiting mTORC1 signalling pathway in gastric cancer

“…Okamoto et al revealed high NUSAP1 expression was related to more advanced T stage and inhibiting NUSAP1 resulted in the suppression of cell proliferation in Oral Squamous Cell Carcinoma (OSCC). Similar biological functions of NUSAP1 were also observed in other malignancies, including breast cancer, hepatocellular carcinoma (HCC), glioblastoma multiforme (GBM), colorectal cancer, astrocytoma, glioma, renal cell carcinoma, and prostate cancer . And previous studies also reported downregulating NUSAP1 could enhance the susceptibility to epirubicin in invasive breast cancer and the anti‐tumour effect of paclitaxel in OSCC .…”

“…And previous studies also reported downregulating NUSAP1 could enhance the susceptibility to epirubicin in invasive breast cancer and the anti‐tumour effect of paclitaxel in OSCC . In addition, high NUSAP1 expression predicted shorter survival in breast cancer, HCC, GBM, colon cancer, and glioma . However, the role of NUSAP1 in GC remains undetermined.…”

NUSAP1 and KIAA0101 downregulation by neo-adjuvant therapy is associated with better outcome and survival in breast cancer.

“…NUSAP1 overexpression has been described in bladder, cervix, colon, glioblastoma, liver, lung, oral squamous cell carcinoma, prostrate, kidney, and breast [24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39] cancers. Multiple studies have correlated its over-expression with a poor prognosis [22,28,30,32,36,37,40,41]. Zhang et al [37] demonstrated that down-regulation of NUSAP1 suppressed proliferation, migration and invasion of MCF7 cells by disturbing the regulation of CDK1 and DLGAP5, and reported increased susceptibility to epirubicin [37].…”

NUSAP1 potentiates chemoresistance in glioblastoma through its SAP domain to stabilize ATR

“…21 NUSAP1 is also highly expressed in astrocytoma. 20,30,31 Despite the extensive study of NUSAP1, whether NUSAP1 participates in DNA damage as well as chemotherapeutic resistance in GBM remains unclear; herein, the role of NUSAP1 in GBM was investigated. This study indicates that NUSAP1 acts as a tumor-related gene in GBM, and that NUSAP1 inhibits cell proliferation and induces apoptosis and DNA damage in GBM.…”