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Updated: Jan 1, 2026

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The Mir181ab1 cluster promotes KRAS-driven oncogenesis and progression in lung and pancreas

Karmele Valencia1,2,3, Oihane Erice1, Kaja Kostyrko4

  • 1University of Navarra, Center for Applied Medical Research, Program in Solid Tumors, Pamplona, Spain.

The Journal of Clinical Investigation
|December 25, 2019
PubMed

Insights

The microRNA (miRNA) cluster miR181ab1 is crucial for KRAS-driven lung and pancreatic cancers. Targeting this miRNA cluster may offer new therapeutic strategies for these aggressive cancers.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • KRAS-driven cancers lack effective therapies, necessitating novel molecular targets.
  • MicroRNAs (miRNAs) are key regulators of cellular processes and oncogenesis.

Purpose of the Study:

  • To investigate the role of the miR181ab1 cluster in KRAS-driven oncogenesis.
  • To identify miR181ab1 as a potential therapeutic target for KRAS-mutated cancers.

Main Methods:

  • Utilized genetically engineered mouse models of Kras-driven lung and pancreatic cancer.
  • Performed miRNA depletion and overexpression studies in human cancer cell lines.
  • Analyzed miR181ab1-regulated genes impacting cancer phenotypes.

Main Results:

  • Ablation of Mir181ab1 in mouse models inhibited tumor initiation and progression.
  • miR181a1 and miR181b1 exhibited nonredundant roles in rescuing the Mir181ab1-loss phenotype.
  • miR181ab1 depletion impaired cancer cell proliferation and 3D growth, while overexpression enhanced it.

Conclusions:

  • The miR181ab1 cluster is a critical modulator of KRAS-driven oncogenesis.
  • miR181ab1 plays a significant role in tumor initiation and progression.
  • miR181ab1 represents a promising therapeutic target for KRAS-mutated lung and pancreatic cancers.
Keywords:
Mouse modelsNoncoding RNAsOncogenesOncology

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