NUSAP1 gene silencing inhibits cell proliferation, migration and invasion through inhibiting DNMT1 gene expression in human colorectal cancer

Han, Guoda; Wei, Zheng-Guo; Cui, Hao; Zhang, Wei; Wei, Xiaonan; Lu, Zhiliang; Bai, Xiyong

doi:10.1016/j.yexcr.2018.03.039

Cited by 50 publications

(46 citation statements)

References 24 publications

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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%

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%

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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“…13 In colorectal cancer, NUSAP1 knockdown induced apoptosis and inhibited tumor cell migration, invasion, cell proliferation and EMT by inhibiting the expression of DNA methyltransferase 1 (DNMT1), indicating that NUSAP1 can be used as an independent prognostic biomarker. 14 In prostate cancer, high NUSAP1 expression promoted prostate cancer cell proliferation and invasion with the loss of RB1 via the RB1/E2F1 axis. 15 However, the functional roles of NUSAP1 in BLCA are not clear.…”

Section: Discussionmentioning

confidence: 99%

<p>Nucleolar and Spindle Associated Protein 1 (NUSAP1) Promotes Bladder Cancer Progression Through the TGF-β Signaling Pathway</p>

Gao

Yin

Tong

et al. 2020

OTT

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Purpose: NUSAP1 has been reported to be involved in the progression of several types of cancer. However, its expression and exact role in bladder cancer (BLCA) remains elusive. The aim of this study was to determine the expression and role of NUSAP1 in BLCA. Methods: Tissue microarray, real-time PCR, Western blot and immunohistochemistry assays were carried out to determine NUSAP1 expression in BLCA tissues and cells. The biological roles of NUSAP1 were investigated using CCK-8, EdU labeling, flow cytometry, Transwell, and wound healing assays. Additionally, the effect of NUSAP1 on epithelialmesenchymal transition (EMT) was investigated by Western blotting and real-time PCR. Results: We found that NUSAP1 was upregulated in BLCA, and its expression was closely related to the poor prognosis of patients. Subsequently, we transfected 5637 and T24 cell lines with NUSAP1 siRNA and an NUSAP1 overexpression plasmid, respectively. NUSAP1 downregulation in 5637 cells inhibited cell proliferation, migration, and invasiveness and enhanced chemosensitivity to gemcitabine, while NUSAP1 overexpression in T24 cells resulted in the inverse effects. Moreover, NUSAP1 regulated EMT via the TGF-β signaling pathway, and when TGF-beta receptor 1 (TGFBR1) was inhibited with the inhibitor SB525334, the invasion and metastasis ability of BLCA cells was significantly suppressed, as well as p-Smad2/3 and vimentin expression. Conclusion: Our above data demonstrate that NUSAP1 contributes to BLCA progression via the TGF-β signaling pathway.

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“…Therefore, identification of TA cell-specific markers would be critical for further characterization of these cells. Based on the transcriptome analysis, we found that NUSAP1 (nucleolar and spindle associated protein 1), which is up-regulated in colorectal cancer (Han et al, 2018a), was specifically expressed in the TA cluster in the ileum, colon, and rectum, just like KI67 ( Fig. 5 A and Fig.…”

Section: Characterization Of Plcs In the Human Large Intestinementioning

confidence: 99%

Single-cell transcriptome analysis reveals differential nutrient absorption functions in human intestine

Wang

Song

Wang

et al. 2019

Journal of Experimental Medicine

288

274

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The intestine plays an important role in nutrient digestion and absorption, microbe defense, and hormone secretion. Although major cell types have been identified in the mouse intestinal epithelium, cell type–specific markers and functional assignments are largely unavailable for human intestine. Here, our single-cell RNA-seq analyses of 14,537 epithelial cells from human ileum, colon, and rectum reveal different nutrient absorption preferences in the small and large intestine, suggest the existence of Paneth-like cells in the large intestine, and identify potential new marker genes for human transient-amplifying cells and goblet cells. We have validated some of these insights by quantitative PCR, immunofluorescence, and functional analyses. Furthermore, we show both common and differential features of the cellular landscapes between the human and mouse ilea. Therefore, our data provide the basis for detailed characterization of human intestine cell constitution and functions, which would be helpful for a better understanding of human intestine disorders, such as inflammatory bowel disease and intestinal tumorigenesis.

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NUSAP1 gene silencing inhibits cell proliferation, migration and invasion through inhibiting DNMT1 gene expression in human colorectal cancer

Cited by 50 publications

References 24 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

<p>Nucleolar and Spindle Associated Protein 1 (NUSAP1) Promotes Bladder Cancer Progression Through the TGF-β Signaling Pathway</p>

Single-cell transcriptome analysis reveals differential nutrient absorption functions in human intestine

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