RNF187 neddylation in pancreatic cancer activates malignancy via IQGAP1-dependent actin cytoskeleton rearrangement

Chengxiao Yang1,2,3, Xinyuan Liu2,3, Wenbo Yang1,2

  • 1Department of Hepatobiliary and Pancreas Surgery, Qunli District, The First Affiliated Hospital of Harbin Medical University, Harbin, China.

Oncogene
|November 25, 2025
PubMed

Insights

Neddylation stabilizes RNF187, promoting pancreatic cancer (PC) cell growth and invasion. RNF187 further boosts PC malignancy by upregulating IQGAP1 and MYH9, offering a potential therapeutic target for pancreatic cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Neddylation is a key post-translational modification in cancer.
  • Its role in pancreatic cancer (PC) pathogenesis is not well understood.
  • Identifying novel regulators of PC is crucial for therapeutic development.

Purpose of the Study:

  • To investigate the role of neddylation-related molecules in pancreatic cancer.
  • To identify key molecules involved in PC progression.
  • To elucidate the molecular mechanisms by which RNF187 promotes PC malignancy.

Main Methods:

  • Screening of neddylation-related molecules in PC.
  • In vitro and in vivo assays to assess cell proliferation and invasion.
  • Ubiquitination assays to analyze protein degradation pathways.
  • Western blotting and qRT-PCR to measure protein and gene expression levels.

Main Results:

  • RNF187 was identified as significantly overexpressed in PC tissues and cell lines.
  • NEDD8 binding to RNF187 inhibited its degradation, increasing RNF187 protein levels.
  • RNF187 overexpression enhanced PC cell proliferation and invasion.
  • RNF187 upregulated IQGAP1 and MYH9, promoting actin cytoskeleton rearrangement and PC malignancy.

Conclusions:

  • Neddylation of RNF187 enhances pancreatic cancer malignancy.
  • The IQGAP1/MYH9 signaling axis is critical for RNF187-mediated PC progression.
  • RNF187 represents a promising therapeutic target for pancreatic cancer treatment.