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The Soft Agar Colony Formation Assay
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RANBP9 and RANBP10 cooperate in regulating non-small cell lung cancer proliferation.

Arturo Orlacchio1,2, Yasuko Kajimura1,3, Lara Rizzotto4

  • 1Department of Cancer Biology and Genetics, College of Medicine, Arthur G. James Comprehensive Cancer Center (OSUCCC), The Ohio State Universityand , Columbus, OH, USA.

Journal of Experimental & Clinical Cancer Research : CR
|August 29, 2025
PubMed
Summary

Scorpins (RANBP9 and RANBP10) modulate non-small cell lung cancer (NSCLC) cell proliferation by regulating the CTLH complex. Their ratio impacts proliferation, suggesting potential therapeutic targets for NSCLC treatment.

Keywords:
ARMC8CTLH complexGID complexGID4GID8Lung cancerMAEAMKLN1NSCLCNon-small cell lung cancerRANBP10RANBP9RANBPMRMND5ARMND5BSCORPINTWA1WDR26YPEL5

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Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • RANBP9 and RANBP10, known as Scorpins, are key components of the C-terminal to LisH (CTLH) complex, a poorly understood E3 ligase.
  • The specific role of Scorpins in non-small cell lung cancer (NSCLC) has not been previously elucidated.

Purpose of the Study:

  • To investigate the independent and cooperative functions of RANBP9 and RANBP10 in NSCLC.
  • To determine the impact of Scorpins on cellular proteome and ubiquitylome in NSCLC.
  • To explore the potential of Scorpins as therapeutic targets in NSCLC.

Main Methods:

  • Utilized stable loss-of-function and overexpression inducible cell lines to study RANBP9 and RANBP10.
  • Analyzed expression of RANBP9 and RANBP10 in NSCLC patient tumors and public datasets.
  • Investigated proteome and ubiquitylome changes associated with Scorpins in NSCLC cell lines.

Main Results:

  • Both RANBP9 and RANBP10 are expressed in NSCLC cells and can independently form functional CTLH complexes.
  • The ratio of RANBP9 to RANBP10 influences NSCLC cell proliferation, with a higher ratio correlating with increased proliferation.
  • Overexpression of RANBP10 reduced NSCLC cell proliferation and decreased levels of proliferation-associated proteins, including DNA replication factors.

Conclusions:

  • Scorpins function antagonistically as a rheostat, modulating CTLH complex ubiquitylation output to regulate NSCLC cell proliferation.
  • The findings suggest that Scorpins are critical regulators of biological processes in NSCLC.
  • RANBP9 and RANBP10 represent promising therapeutic targets for NSCLC treatment.