Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
BMC Cancer
Published in: BMC Cancer 1/2024

Open Access 01-12-2024 | Research

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

Authors: Yuan Liu, Rong Tang, Qing-Cai Meng, Si Shi, Jin Xu, Xian-Jun Yu, Bo Zhang, Wei Wang

Published in: BMC Cancer | Issue 1/2024

Login to get access

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.
Appendix
Available only for authorised users
Literature
1.
2.
Brayer KJ, Hanson JA, Cingam S, Martinez C, Ness SA, Rabinowitz I. The inflammatory response of human pancreatic cancer samples compared to normal controls. PLoS One. 2023;18(11):e0284232.PubMedPubMedCentralCrossRef
3.
Huang H, Wright S, Zhang J, Brekken RA. Getting a grip on adhesion: cadherin switching and collagen signaling. Biochim Biophys Acta Mol Cell Res. 2019;1866(11):118472.PubMedCrossRef
4.
Lee M, Marinoni I, Irmler M, Psaras T, Honegger JB, Beschorner R, et al. Transcriptome analysis of MENX-associated rat pituitary adenomas identifies novel molecular mechanisms involved in the pathogenesis of human pituitary gonadotroph adenomas. Acta Neuropathol. 2013;126(1):137–50.PubMedPubMedCentralCrossRef
5.
Strobel O, Neoptolemos J, Jäger D, Büchler MW. Optimizing the outcomes of pancreatic cancer surgery. Nat Rev Clin Oncol. 2019;16(1):11–26.PubMedCrossRef
6.
7.
8.
Feng H, Gu ZY, Li Q, Liu QH, Yang XY, Zhang JJ. Identification of significant genes with poor prognosis in ovarian cancer via bioinformatical analysis. J Ovarian Res. 2019;12(1):35.PubMedPubMedCentralCrossRef
9.
Qiu JJ, Xu L, Zeng XH, Wu ZR, Wang Y, Wang Y, et al. NUSAP1 promotes the metastasis of breast cancer cells via the AMPK/PPARγ signaling pathway. Ann Transl Med. 2021;9(22):1689.PubMedPubMedCentralCrossRef
10.
Hou J, Lu ZQ, Liu XH, Luo BF, Qu GY, Xu Y, et al. Increased NUSAP1 expression is associated with lymph node metastasis and survival prognosis in bladder urothelial carcinoma. Sci Rep. 2022;12(1):7003.PubMedPubMedCentralCrossRef
11.
Barrett T, Wilhite SE, Ledoux P, Evangelista C, Kim IF, Tomashevsky M, Marshall KA, Phillippy KH, Sherman PM, Holko M, et al. NCBI GEO: archive for functional genomics data sets–update. Nucleic Acids Res. 2013;41(Database issue):D991-995.PubMed
12.
Zhang Y, Pang SJ, Sun B, Zhang MB, Jiao XX, Lai LY, et al. ELOVLs predict distinct prognosis value and immunotherapy efficacy in patients with hepatocellular carcinoma. Front Oncol. 2022;12:884066.PubMedPubMedCentralCrossRef
13.
14.
15.
Meng Q, Shi S, Liang C, Liang D, Hua J, Zhang B, et al. Abrogation of glutathione peroxidase-1 drives EMT and chemoresistance in pancreatic cancer by activating ROS-mediated Akt/GSK3β/Snail signaling. Oncogene. 2018;37(44):5843–57.PubMedCrossRef
16.
Liang C, Shi S, Qin Y, Meng Q, Hua J, Hu Q, et al. Localisation of PGK1 determines metabolic phenotype to balance metastasis and proliferation in patients with SMAD4-negative pancreatic cancer. Gut. 2020;69:888–900.PubMedCrossRef
17.
Ji S, Qin Y, Liang C, Huang R, Shi S, Liu J, et al. FBW7 (F-box and WD repeat domain-containing 7) negatively regulates glucose metabolism by targeting the c-Myc/TXNIP (thioredoxin-binding protein) axis in pancreatic cancer. Clin Cancer Res. 2016;22:3950–60.PubMedCrossRef
18.
Liang C, Yu XJ, Guo XZ, Sun MH, Wang Z, Song Y, et al. MicroRNA-33a-mediated downregulation of Pim-3 kinase expression renders human pancreatic cancer cells sensitivity to gemcitabine. Oncotarget. 2015;6:14440–55.PubMedPubMedCentralCrossRef
19.
Akl L, Abd El-Hafeez AA, Ibrahim TM, Salem R, Marzouk HMM, El-Domany RA. Identification of novel piperazine-tethered phthalazines as selective CDK1 inhibitors endowed with in vitro anticancer activity toward the pancreatic cancer. Eur J Med Chem. 2022;243:114704.PubMedCrossRef
20.
Tanaka T, Okada R, Hozaka Y, Wada M, Moriya S, Satake S, et al. Molecular pathogenesis of pancreatic ductal adenocarcinoma: impact of miR-30c-5p and miR-30c-2-3p regulation on oncogenic genes. Cancers (Basel). 2020;12(10):2731.PubMedCrossRef
21.
Li Z, Zhuang H, Chen X, Zhang Y, Ma Z, Wang S, et al. Identification of MBOAT2 as an unfavorable biomarker correlated with KRAS activation and reduced CD8+ T-cell infiltration in pancreatic cancer. J Oncol. 2022;2022:4269733.PubMedPubMedCentral
22.
Timaner M, Shaked Y. Elucidating the roles of ASPM isoforms reveals a novel prognostic marker for pancreatic cancer. J Pathol. 2020;250(2):123–5.PubMedCrossRef
23.
24.
Xu Y, Li X, Su X. iTRAQ‑based proteomics analysis of the therapeutic effects of combined anticancer bioactive peptides and oxaliplatin on gastric cancer cells. Oncol Rep. 2020;43(1):201–17.PubMed
25.
Neoptolemos JP, Kleeff J, Michl P, Costello E, Greenhalf W, Palmer DH. Therapeutic developments in pancreatic cancer: current and future perspectives. Nat Rev Gastroenterol Hepatol. 2018;15(6):333–48.PubMedCrossRef
26.
27.
Deng YJ, Ma HY, Hao JY, Xie QQ, Zhao RC. MCM2 and NUSAP1 are potential biomarkers for the diagnosis and prognosis of pancreatic cancer. Biomed Res Int. 2020;2020:8604340.PubMedPubMedCentralCrossRef
28.
Guo H, Zou J, Zhou L, Zhong M, He Y, Huang S, et al. NUSAP1 promotes gastric cancer tumorigenesis and progression by stabilizing the YAP1 protein. Front Oncol. 2021;10:591698.PubMedPubMedCentralCrossRef
29.
Wu Y, Liu HX, Gong YF, Zhang B, Chen WX. ANKRD22 enhances breast cancer cell malignancy by activating the Wnt/β-catenin pathway via modulating NuSAP1 expression. Bosn J Basic Med Sci. 2021;21(3):294–304.PubMedPubMedCentral
30.
Gao SY, Gang J, Yu M, Xin GS, Tan HX. Computational analysis for identification of early diagnostic biomarkers and prognostic biomarkers of liver cancer based on GEO and TCGA databases and studies on pathways and biological functions affecting the survival time of liver cancer. BMC Cancer. 2021;21(1):791.PubMedPubMedCentralCrossRef
31.
32.
33.
Cerami E, Gao J, Dogrusoz U, Gross BE, Sumer SO, Aksoy BA, et al. The cBio cancer genomics portal: an open platform for exploring multidimensional cancer genomics data. Cancer Discov. 2012;2(5):401–4.PubMedCrossRef
34.
Zhang H, Lin YD, Zhuang MX, Zhu L, Dai YM, Lin MB. Screening and identification of CNIH4 gene associated with cell proliferation in gastric cancer based on a large-scale CRISPR-Cas9 screening database DepMap. Gene. 2022;850:146961.PubMedCrossRef
35.
Shi B, Ding J, Qi J, Gu Z. Characteristics and prognostic value of potential dependency genes in clear cell renal cell carcinoma based on a large-scale CRISPR-Cas9 and RNAi screening database DepMap. Int J Med Sci. 2021;18(9):2063–75.PubMedPubMedCentralCrossRef
36.
Fu T, Dai LJ, Wu SY, Xiao Y, Ma D, Jiang YZ, et al. Spatial architecture of the immune microenvironment orchestrates tumor immunity and therapeutic response. J Hematol Oncol. 2021;14(1):98.PubMedPubMedCentralCrossRef
37.
Dai Y, Qiang W, Lin K, Gui Y, Lan X, Wang D. An immune-related gene signature for predicting survival and immunotherapy efficacy in hepatocellular carcinoma. Cancer Immunol Immunother. 2021;70(4):967–79.PubMedCrossRef
38.
Li Y, Shen J, Cheng CS, Gao H, Zhao J, Chen L. Overexpression of pyruvate dehydrogenase phosphatase 1 promotes the progression of pancreatic adenocarcinoma by regulating energy-related AMPK/mTOR signaling. Cell Biosci. 2020;10:95.PubMedPubMedCentralCrossRef
39.
Chen W, Zhang Z, Yung KK, Ko JK. MUC1 is responsible for the pro-metastatic potential of calycosin in pancreatic ductal adenocarcinoma. Am J Cancer Res. 2022;12(7):3242–58.PubMedPubMedCentral
40.
Xu Q, Wu N, Li X, Guo C, Li C, Jiang B, et al. Inhibition of PTP1B blocks pancreatic cancer progression by targeting the PKM2/AMPK/mTOC1 pathway. Cell Death Dis. 2019;10(12):874.PubMedPubMedCentralCrossRef
41.
Song CF, Hu YH, Mang ZG, Ye Z, Chen HD, Jing DS, et al. Hernandezine induces autophagic cell death in human pancreatic cancer cells via activation of the ROS/AMPK signaling pathway. Acta Pharmacol Sin. 2023;44(4):865–76.PubMedCrossRef
Metadata
Title
NUSAP1 promotes pancreatic ductal adenocarcinoma progression by drives the epithelial-mesenchymal transition and reduces AMPK phosphorylation
Authors
Yuan Liu
Rong Tang
Qing-Cai Meng
Si Shi
Jin Xu
Xian-Jun Yu
Bo Zhang
Wei Wang
Publication date
01-12-2024
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2024
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-024-11842-5

Other articles of this Issue 1/2024

BMC Cancer 1/2024 Go to the issue

Research

Enrichment of colibactin-associated mutational signatures in unexplained colorectal polyposis patients

Study Protocol

Pragmatic nationwide master observational trial based on genomic alterations in advanced solid tumors: KOrean Precision Medicine Networking Group Study of MOlecular profiling guided therapy based on genomic alterations in advanced Solid tumors (KOSMOS)-II study protocol KCSG AL-22–09

Research

EGR1 mediates MDR1 transcriptional activity regulating gemcitabine resistance in pancreatic cancer

Research

The Hippo pathway terminal effector TAZ/WWTR1 mediates oxaliplatin sensitivity in p53 proficient colon cancer cells

Research

MUC1 promotes cervical squamous cell carcinoma through ERK phosphorylation-mediated regulation of ITGA2/ITGA3

Research

An evaluation of nutritional impact symptoms and their association with reduced dietary intake in patients with solid tumors at tertiary care hospitals: a multicenter, cross-sectional study from palestine
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits