SPDEF drives pancreatic adenocarcinoma progression via transcriptional upregulation of S100A16 and activation of the PI3K/AKT signaling pathway

Authors

  • Hang Jiang Department of Hepatobiliary and Pancreatic Surgery, The Third People's Hospital of Yunnan Province, Kunming, Yunnan, China
  • Zhiqian Xue Department of Hepatobiliary and Pancreatic Surgery, The Third People's Hospital of Yunnan Province, Kunming, Yunnan, China
  • Liping Zhao Department of Hepatobiliary and Pancreatic Surgery, The Third People's Hospital of Yunnan Province, Kunming, Yunnan, China
  • Boyuan Wang Shanghai Qibao Dwight High School, Shanghhai, China
  • Chenfei Wang Department of Emergency, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
  • Haihan Song Department of Hepatobiliary and Pancreatic Surgery, The Third People's Hospital of Yunnan Province, Kunming, Yunnan, China; Department of Immunology, DICAT Biomedical Computation Centre, Vancouver, BC, Canada; Central Lab, Shanghai Key Laboratory of Pathogenic Fungi Medical Testing, Shanghai Pudong New Area People's Hospital, Shanghai, China https://orcid.org/0009-0006-7753-8628
  • Jianjun Sun Department of Hepatobiliary and Pancreatic Surgery, The Third People's Hospital of Yunnan Province, Kunming, Yunnan, China

DOI:

https://doi.org/10.17305/bb.2024.10346

Keywords:

Pancreatic adenocarcinoma (PAAD), Sam's pointed domain-containing ETS transcription factor (SPDEF), S100A16, PI3K/AKT signaling pathway

Abstract

Pancreatic adenocarcinoma (PAAD) is a notably aggressive malignancy with limited treatment options and an unfavorable prognosis for patients. We aimed to investigate molecular mechanisms by which Sam's pointed domain-containing ETS transcription factor (SPDEF) exerts effects on PAAD progression. We analyzed differentially expressed genes (DEGs) and their integration with ETS family members using the The Cancer Genome Atlas (TCGA) database, hence identifying SPDEF as a core gene in PAAD. Kaplan-Meier survival analysis confirmed SPDEF’s prognostic potential. In vitro experiments validated the association with cell proliferation and apoptosis, affecting pancreatic cancer cell dynamics. We detected increased SPDEF expression in PAAD tumor samples. Our in vitro studies revealed that SPDEF regulates mRNA and protein expression levels, and significantly affects cell proliferation. Moreover, SPDEF was associated with reduced apoptosis and enhanced cell migration and invasion. In-depth analysis of SPDEF-targeted genes revealed four crucial genes for advanced prognostic model, among which S100A16 was significantly correlated with SPDEF. Mechanistic analysis showed that SPDEF enhances the transcription of S100A16, which in turn enhances PAAD cell migration, proliferation, and invasion by activating the PI3K/AKT signaling pathway. Our study revealed the critical role of SPDEF in promoting PAAD by upregulating S100A16 transcription and stimulating the PI3K/AKT signaling pathway. This knowledge deepened our understanding of pancreatic cancer's molecular progression and unveiled potential therapeutic strategies targeting SPDEF-driven pathways.

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SPDEF drives pancreatic adenocarcinoma progression via transcriptional upregulation of S100A16 and activation of the PI3K/AKT signaling pathway

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Published

06-09-2024

Data Availability Statement

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Research article

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How to Cite

1.
SPDEF drives pancreatic adenocarcinoma progression via transcriptional upregulation of S100A16 and activation of the PI3K/AKT signaling pathway. Biomol Biomed [Internet]. 2024 Sep. 6 [cited 2024 Oct. 5];24(5):1231–1243. Available from: https://www.bjbms.org/ojs/index.php/bjbms/article/view/10346