NUSAP1 promotes pancreatic ductal adenocarcinoma progression by drives the epithelial-mesenchymal transition and reduces AMPK phosphorylation

Abstract

Background Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis, and its molecular mechanisms are unclear. Nucleolar and spindle-associated protein 1 (NUSAP1), an indispensable mitotic regulator, has been reported to be involved in the development of several types of tumors. The biological function and molecular mechanism of NUSAP1 in PDAC remain controversial. This study explored the effects and mechanism of NUSAP1 in PDAC. Methods Differentially expressed genes (DEGs) were screened. A protein‒protein interaction (PPI) network was constructed to identify hub genes. Experimental studies and tissue microarray (TMA) analysis were performed to investigate the effects of NUSAP1 in PDAC and explore its mechanism. Results Network analysis revealed that NUSAP1 is an essential hub gene in the PDAC transcriptome. Genome heterogeneity analysis revealed that NUSAP1 is related to tumor mutation burden (TMB), loss of heterozygosity (LOH) and homologous recombination deficiency (HRD) in PDAC. NUSAP1 is correlated with the levels of infiltrating immune cells, such as B cells and CD8 T cells. High NUSAP1 expression was found in PDAC tissues and was associated with a poor patient prognosis. NUSAP1 promoted cancer cell proliferation, migration and invasion, drives the epithelial-mesenchymal transition and reduces AMPK phosphorylation. Conclusions NUSAP1 is an essential hub gene that promotes PDAC progression and leads to a dismal prognosis by drives the epithelial-mesenchymal transition and reduces AMPK phosphorylation.

SKA3 Expression as a Prognostic Factor for Patients with Pancreatic Adenocarcinoma

“…In studies conducted on pancreatic cancer cells, BUB1 was identified as a promoter of cell proliferation, migration and gemcitabine resistance [24]. Both ASPM and BUB1 interact with UBE2C, KIF23, KIF2C, KIF11, NUF2, CDK1, BUB1B and NUSAP1, each of which has previously been associated with the initiation and/or progression of PAAD [25][26][27][28][29][30][31][32]. The results of our functional enrichment analysis suggest that SKA3 is correlated with genes that promote proliferation, as well as those responsible for ensuring the high fidelity of chromosome segregation.…”

Conduction and validation of a novel mitotic spindle assembly related signature in hepatocellular carcinoma: prognostic prediction, tumor immune microenvironment and drug susceptibility

“…NUSAP1 serves as a pivotal oncogenic factor in pancreatic ductal adenocarcinoma, driving proliferation, migration, and epithelial-mesenchymal transition, while inhibiting the AMPK signaling pathway. Elevated NUSAP1 expression is associated with unfavorable prognosis ( Liu et al, 2024 ). Furthermore, heightened expression of TPX2 in HCC promotes cell proliferation and invasion through AKT signaling activation and upregulation of MMP2/9, underscoring its potential as a therapeutic target for hepatocellular carcinoma ( Liu et al, 2014 ).…”