Nucleolar spindle‐associated protein 1 promotes tumorigenesis and predicts poor prognosis in human esophageal squamous cell carcinoma

Abstract

The microtubule binding protein, nucleolar spindle-associated protein 1 (NUSAP1), has a crucial function in mitosis and its expression is closely associated with carcinogenesis. Herein, we aimed to determine the function of NUSAP1 in the development of human esophageal squamous cell carcinoma (ESCC), and the association of NUSAP1 expression with ESCC. Immunohistochemical staining of ESCC tissue sections indicated that NUSAP1 was expressed to a higher degree in tumor tissues than in adjacent nontumor tissues. NUSAP1 levels were relevant closely to histological differentiation (P = 0.049). Overall survival was longer in patients with lower NUSAP1 levels (P < 0.001). NUSAP1 expression (P = 0.002), histological differentiation (P < 0.001), tumor depth (P = 0.045), lymph node metastases (P < 0.001), and tumor-node-metastasis staging (P = 0.008) were greatly associated with overall survival using univariate analysis. Multivariate analysis suggested that histological differentiation (P = 0.014) and NUSAP1 expression (P = 0.026) could be independent prognostic markers for ESCC. Additionally, the biological behavior of ESCC cells was investigated in vitro and in vivo. Suppression of NUSAP1 inhibited cellular proliferation and invasion, and induced cell cycle arrest and apoptosis in vitro. More importantly, knockdown of NUSAP1 led to inhibition of tumor formation in nude mice. These findings indicated that NUSAP1 is a potential prognostic biomarker in ESCC, and is an ESCC oncogene. Thus, NUSAP1 could represent a therapeutic target for ESCC. K E Y W O R D Sesophageal squamous cell carcinoma, nucleolar spindle-associated protein 1, tumorigenesis

Analyzing Roles of NUSAP1 From Clinical, Molecular Mechanism and Immune Perspectives in Hepatocellular Carcinoma

“…Nucleolar and spindle-associated protein 1 (NUSAP1) is a nucleolar-spindle-associated protein that plays a role in spindle microtubule organization, which belongs to the NUSP1 family ( Raemaekers et al, 2003 ; Petry, 2016 ). Previous studies had demonstrated that the overexpression of NUSAP1 was observed in many human neoplasms including colon cancer ( Han et al, 2018 ; Liu et al, 2018 ), astrocytoma ( Wu et al, 2017 ), glioblastoma multiforme ( Qian et al, 2018 ), renal cell carcinoma ( Fang et al, 2016 ), prostate cancer ( Gulzar et al, 2013 ; Gordon et al, 2015 , 2017 ), oral squamous cell carcinoma ( Okamoto et al, 2015 ), breast cancer ( Kretschmer et al, 2011 ; Chen et al, 2015 ), cervical carcinoma ( Li et al, 2019 ), and esophageal squamous cell carcinoma ( Guan et al, 2019 ). Besides, many studies also showed that overexpression of NUSAP1 was associated with poor survival of colon cancer ( Liu et al, 2018 ), astrocytoma ( Wu et al, 2017 ), glioblastoma multiforme ( Qian et al, 2018 ), renal cell carcinoma ( Fang et al, 2016 ), prostate cancer ( Gordon et al, 2017 ), breast cancer ( Chen et al, 2015 ), and esophageal squamous cell carcinoma ( Guan et al, 2019 ).…”

Identification and clinical validation of NUSAP1 as a novel prognostic biomarker in ovarian cancer

“…High NUSAP1 expression predicts poor prognosis in astrocytoma [12], breast cancer [13], esophageal squamous cell carcinoma [10], and colon cancer [14]. However, opposite results were obtained in the prognostic analysis of cervical cancer [15,32].…”

“…Its expression peaks when cells transition from the G2 phase of the cell cycle to the mitotic phase [7]. NUSAP1 is highly expressed in multiple malignant tumors, such as breast cancer [8], hepatocellular carcinoma [9], esophageal squamous cell carcinoma [10], and glioblastoma [11]. High NUSAP1 expression promotes malignant biological behaviors, such as tumor invasion and metastasis, and is associated with poor prognosis in patients with astrocytoma [12], breast cancer [13], colon cancer [14], and cervical cancer [15].…”

Analyzing the value of NUSAP1 in hepatocellular carcinoma from clinical and molecular mechanism perspectives: Bioinformatics-based approach.

“…Nucleolar and spindle-associated protein 1 (NUSAP1) is a nucleolar-spindle-associated protein that plays a role in spindle microtubule organization, which belongs to the NUSP1 family [24,25]. Before our study, many studies had demonstrated that the overexpression of NUSAP1 was observed in many human neoplasms including colon cancer [26,27], astrocytoma [28], glioblastoma multiforme [29], renal cell carcinoma [30], prostate cancer [31][32][33], oral squamous cell carcinoma [34], breast cancer [35,36], cervical carcinoma [37] and esophageal squamous cell carcinoma [38]. Besides, many studies also showed that overexpression of NUSAP1 was associated with poor survival of colon cancer [26], astrocytoma [28], glioblastoma multiforme [29], renal cell carcinoma [30], prostate cancer [33], breast cancer [36] and esophageal squamous cell carcinoma [38].…”