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Published on: February 2, 2021

DNER drives glycolytic reprogramming in renal cell carcinoma by activating the JAK2/STAT3 signaling pathway

Anrui Li1, Jing-Wen Xu1, Jian-Hua Qin2

  • 1Department of Urology, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, China.

Frontiers in Immunology
|June 8, 2026
PubMed
Abstract

Insights

The study identifies DNER as a key driver in clear cell renal cell carcinoma (ccRCC) progression. DNER promotes tumor growth by altering cell metabolism and creating an immunosuppressive tumor microenvironment, suggesting it as a potential therapeutic target for ccRCC.

Area of Science:

  • Oncology
  • Molecular Biology
  • Immunology

Background:

  • Clear cell renal cell carcinoma (ccRCC) presents diagnostic and therapeutic challenges.
  • Understanding the molecular mechanisms driving ccRCC progression is crucial for developing effective treatments.

Purpose of the Study:

  • To investigate the role of DNER (Developmental Netrin Response) in ccRCC progression.
  • To elucidate the molecular pathways through which DNER influences ccRCC tumor growth and the tumor microenvironment.

Main Methods:

  • Integrated bioinformatic analyses with experimental validation (in vitro and in vivo).
  • Systematic screening of metabolism-related genes to identify hub genes.
  • Functional assays and mechanistic studies on DNER-interacting proteins and signaling pathways.

Main Results:

  • DNER was identified as a hub gene associated with metabolic pathway activity and immune cell infiltration in ccRCC.
  • DNER promotes ccRCC cell proliferation both in vitro and in vivo.
  • DNER activates the JAK2/STAT3 pathway, upregulating glycolytic enzymes and promoting M2 macrophage polarization, creating an immunosuppressive microenvironment.

Conclusions:

  • DNER drives ccRCC progression by linking metabolic reprogramming to an immunosuppressive microenvironment via the JAK2/STAT3 signaling axis.
  • DNER represents a potential therapeutic target for ccRCC.
  • DNER overexpression may influence sensitivity to PARP inhibitors like Olaparib.
Keywords:
DNERclear cell renal cell carcinomaglycolysismetabolic reprogrammingolaparibtumor microenvironment

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