Nucleolar and spindle‐associated protein 1 is a tumor grade correlated prognosis marker for glioma patients

Zhu, Tao; Xie, Ping; Gao, Yuanfeng; Huang, Ma-Sha; Li, Xi; Zhang, Wei; Zhou, Hong‐Hao; Liu, Zhao‐Qian

doi:10.1111/cns.12803

Cited by 27 publications

(27 citation statements)

References 36 publications

(40 reference statements)

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“…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 .…”

Section: Introductionsupporting

confidence: 59%

“…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.…”

Section: Introductionmentioning

confidence: 99%

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

Lin

et al. 2019

Cell Biochemistry & Function

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Gastric cancer (GC) is one of the most common causes of cancer-related death worldwide, and outstanding biomarkers for therapeutic targets or predicting GC survival are still lacking. Increasing evidence indicated that nucleolar and spindle associated protein 1 (NUSAP1) involved in regulating the progression of various cancers; however, its specific role in GC remained unclear. In this study, we found that NUSAP1 was upregulated in the GC tissues and cell lines via analysing data from The Cancer Genome Atlas (TCGA), gene expression omnibus (GEO), qRT-PCR, and western blot assays. Patients with high NUSAP1 expression levels showed shorter freeprogression survival (FPS), larger tumour size, and higher lymphatic metastasis rate compared with those with low NUSAP1 expression. Further functional experiments revealed knockdown of NUSAP1 could inhibit the growth, migration, and invasion of GC cells in vitro and vivo. Additionally, silencing NUSAP1 induced G0/G1 phase arrest, apoptosis, and suppressed the epithelial-mesenchymal transition (EMT) process. Finally, we performed gene set enrichment analysis (GSEA) and observed NUSAP1 was positive with mTORC1 signalling pathway, which was verified by the subsequent immunoblotting. In conclusion, our findings suggested that NUSAP1 contributed to GC progression and may act as a potential therapeutic target for GC.Significance of the study: Our results firstly illuminated that NUSAP1 expression was significantly upregulated in GC tissues and predicted poor FPS. Silencing it could attenuate GC progression via inhibiting mTORC1 signalling pathway. Hence, NUSAP1 may act as a promising therapy target for GC.

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Section: Introductionsupporting

confidence: 59%

Section: Introductionmentioning

confidence: 99%

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

Lin

et al. 2019

Cell Biochemistry & Function

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“…More and more molecular biomarkers are identified and applied to improve the diagnosis and treatment of gliomas. However, the prognosis of the disease still remains gloomy [3,[33][34][35][36][37]. And also, it is of desperate need to find promising therapeutic targets for glioma.…”

Section: Discussionmentioning

confidence: 99%

Knockdown ATG4C inhibits gliomas progression and promotes temozolomide chemosensitivity by suppressing autophagic flux

Wen

Zeng

Chen

et al. 2019

J Exp Clin Cancer Res

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Background: Gliomas are the most common primary tumors in central nervous system. Despite advances in diagnosis and therapy, the prognosis of glioma remains gloomy. Autophagy is a cellular catabolic process that degrades proteins and damaged organelles, which is implicated in tumorigenesis and tumor progression. Autophagy related 4C cysteine peptidase (ATG4C) is an autophagy regulator responsible for cleaving of pro-LC3 and delipidation of LC3 II. This study was designed to investigate the role of ATG4C in glioma progression and temozolomide (TMZ) chemosensitivity. Methods: The association between ATG4C mRNA expression and prognosis of gliomas patients was analyzed using the TCGA datasets. The role of ATG4C in proliferation, apoptosis, autophagy, and TMZ chemosensitivity were investigated by silencing ATG4C in vivo. Ectopic xenograft nude mice model was established to investigate the effects of ATG4C on glioma growth in vivo. Results: The median overall survival (OS) time of patients with higher ATG4C expression was significantly reduced (HR: 1.48, p = 9.91 × 10 − 7). ATG4C mRNA expression was evidently increased with the rising of glioma grade (p = 2.97 × 10 − 8). Knockdown ATG4C suppressed glioma cells proliferation by inducing cell cycle arrest at G1 phase. ATG4C depletion suppressed autophagy and triggered apoptosis through ROS accumulation. Depletion of ATG4C suppressed TMZ-activated autophagy and promoted sensitivity of glioma cells to TMZ. Additionally, ATG4C knockdown suppressed the growth of glioma remarkably in nude mice. Conclusion: ATG4C is a potential prognostic predictor for glioma patient. Targeting ATG4C may provide promising therapy strategies for gliomas treatment.

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“…Nucleolar spindle-associated protein 1 (NUSAP1) is a microtubule-associated protein that plays a critical role in various biological functions, including spindle assembly, chromosome segregation, cytokinesis, microtubule crosslinking, bundling and attachment to chromosomes [13][14][15]. Studies have shown that NUSAP1 is involved in human malignancies, including pancreatic adenocarcinoma, glioblastoma, hepatocellular carcinoma, prostate cancer and etc [16][17][18][19][20]. High expression of NUSAP1 is positively correlated with poor prognosis in lung cancer and cervical carcinoma [21,22].…”

Section: Introductionmentioning

confidence: 99%

NUSAP1 Promotes Gastric Cancer Progression Through Regulation of Yap Stability

Guo¹,

Zou²,

Zhou³

et al. 2020

Preprint

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Background:Nucleolar and spindle associated protein (NUSAP1) is involved in tumor initiation, progression and metastasis. However, there are limited studies regarding the role of NUSAP1 in gastric cancer (GC). Methods: The expression profile and clinical significance of NUSAP1 in GC were analysed in online database using GEPIA, Oncomine and KM plotter, which was further confirmed in clinical specimens.The functional role of NUSAP1 were detected utilizing in vitro and in vivo assays. Western blotting, qRT-PCR, the cycloheximide-chase, immunofluorescence staining and Co-immunoprecipitaion (Co-IP) assays were performed to explore the possible molecular mechanism by which NUSAP1 stabilizes YAP protein. Results:In this study, we found that the expression of NUSAP1 was upregulated in GC tissues and correlates closely with progression and prognosis. Additionally, abnormal NUSAP1 expression promoted malignant behaviors of GC cells in vitro and in a xenograft model. Mechanistically, we discovered that NUSAP1 physically interacts with YAP and furthermore stabilizes YAP protein expression, which induces the transcription of Hippo pathway downstream target genes. Furthermore, the effects of NUSAP1 on GC cell growth, migration and invasion were mainly mediated by YAP. Conclusions:Our data demonstrates that the novel NUSAP1-YAP axis exerts an critical role in GC tumorigenesis and progression, and therefore could provide a novel therapeutic target for GC treatment.

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Nucleolar and spindle‐associated protein 1 is a tumor grade correlated prognosis marker for glioma patients

Abstract: NUSAP1 is a potential prognosis marker for glioma patients and therapeutic strategies targeting NUSAP1 might hold promise in improving glioma treatment.

Cited by 27 publications

References 36 publications

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

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

Knockdown ATG4C inhibits gliomas progression and promotes temozolomide chemosensitivity by suppressing autophagic flux

NUSAP1 Promotes Gastric Cancer Progression Through Regulation of Yap Stability

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