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Oncogenic Activities Of UBE2S Mediated By VHL/HIF-1α/STAT3 Signal Via The Ubiquitin-Proteasome System In PDAC

Lei Wang1, Yiyi Liang2, Pengping Li3

  • 1Department of Oncology, Lianyungang Clinical College of Nanjing Medical University, The First People's Hospital of Lianyungang, Lianyungang 222000, Jiangsu, People's Republic of China.

Oncotargets and Therapy
|December 10, 2019
PubMed
Abstract

Insights

Ubiquitin-conjugating enzyme E2S (UBE2S) promotes pancreatic cancer progression by enhancing epithelial-mesenchymal transition (EMT) through the VHL/HIF-1α/STAT3 pathway. UBE2S and CDC20 represent potential therapeutic targets for pancreatic ductal adenocarcinoma (PDAC).

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Ubiquitin-conjugating enzyme E2S (UBE2S) plays a role in various cancers.
  • The specific function and mechanism of UBE2S in pancreatic cancer remain unclear.

Purpose of the Study:

  • To investigate the role and mechanism of UBE2S in pancreatic ductal adenocarcinoma (PDAC).
  • To explore UBE2S as a potential therapeutic target for PDAC.

Main Methods:

  • Analysis of GEO datasets to identify differentially expressed genes (DEGs) in PDAC.
  • Assessment of UBE2S expression using immunohistochemistry and qRT-PCR.
  • In vitro and in vivo assays to evaluate UBE2S function in PDAC cells, including migration and tumor growth.
  • Investigation of the VHL/HIF-1α/STAT3 pathway and epithelial-mesenchymal transition (EMT) markers.

Main Results:

  • UBE2S mRNA and protein levels are significantly upregulated in PDAC tissues.
  • Increased UBE2S expression correlates with lymph node and distant metastasis.
  • UBE2S promotes PDAC cell proliferation, migration, and tumor growth.
  • UBE2S enhances EMT via the VHL/HIF-1α/STAT3 pathway.

Conclusions:

  • UBE2S facilitates PDAC progression by promoting EMT through the VHL/HIF-1α/STAT3 pathway.
  • The ubiquitin-proteasome system is involved in UBE2S-mediated effects.
  • Co-expression of UBE2S and CDC20 may offer novel therapeutic strategies for PDAC patients.
Keywords:
EMTUBE2SVHL/HIF-1α/STAT3 signalingpancreatic cancerthe ubiquitin-proteasome system

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