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

• Published in: Cell biochemistry and function 2020-01, Vol.38 (1), p.28-37
• Main Authors: Ge, Yugang, Li, Qiang, Lin, Linling, Jiang, Mingkun, Shi, Liang, Wang, Biao, Yang, Li, Xu, Zekuan
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis; Biomarkers; Cancer; Cell migration; Cell Movement - drug effects; Cell proliferation; Cell Proliferation - drug effects; Cells, Cultured; Computational Biology; Dose-Response Relationship, Drug; Down-Regulation - drug effects; Drug Screening Assays, Antitumor; EMT; Female; G1 phase; Gastric cancer; Gene expression; Gene set enrichment analysis; Genomes; Humans; Immunoblotting; Male; Mechanistic Target of Rapamycin Complex 1 - antagonists & inhibitors; Mesenchyme; Metastases; Mice; Mice, Inbred BALB C; Mice, Nude; Microtubule-Associated Proteins - biosynthesis; Microtubule-Associated Proteins - genetics; Microtubule-Associated Proteins - metabolism; Middle Aged; mTORC1 signalling; Neoplasms, Experimental - drug therapy; Neoplasms, Experimental - metabolism; Neoplasms, Experimental - pathology; Nucleoli; NUSAP1; prognosis; Signal transduction; Signal Transduction - drug effects; Signaling; Stomach Neoplasms - drug therapy; Stomach Neoplasms - metabolism; Stomach Neoplasms - pathology; Structure-Activity Relationship; Survival; Therapeutic applications; Tumors
• ISSN: 0263-6484; 1099-0844
• DOI: 10.1002/cbf.3444

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 free‐progression 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.