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Updated: Jun 13, 2026

Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer
06:51

Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer

Published on: July 21, 2018

Cell-type Specific Alteration of Dicer1 Accelerates Tumor Progression in Mouse Models of KRAS-driven Lung

Julie Wells1, Richard S Maser1, Rosalinda Doty1

  • 1The Jackson Laboratory, Bar Harbor, Maine.

Biorxiv : the Preprint Server for Biology
|June 12, 2026
PubMed

Insights

Global microRNA (miRNA) disruption accelerates lung cancer progression in a cell-type-specific manner. Our Kras-driven mouse models reveal Dicer1

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • MicroRNAs (miRNAs) play crucial roles in cancer development.
  • Global miRNA disruption effects on cancer progression are not fully understood.
  • Dicer1 is essential for mature miRNA biogenesis.

Purpose of the Study:

  • To investigate the impact of cell-type-specific Dicer1 disruption on Kras-driven lung adenocarcinoma (LUAD) progression.
  • To explore the role of miRNA biosynthesis in LUAD.
  • To develop novel mouse models for studying miRNA function in cancer.

Main Methods:

  • Development of genetically engineered mouse models with cell-type-specific Dicer1 allele deletion.
  • Induction of Kras-driven pulmonary adenocarcinoma.
  • Analysis of tumor progression rates and survival.
  • Comparative studies involving different cell types (club cells and alveolar type 2 cells).

Main Results:

  • Dicer1 disruption accelerated LUAD progression and decreased survival when initiated in club cells and mutated in alveolar type 2 (AT2) cells.
  • Reversing the cell types (initiating in AT2, mutating in club cells) only modestly accelerated tumor progression with no survival impact.
  • These findings highlight a cell-type-dependent and non-cell-autonomous effect of Dicer1 disruption.

Conclusions:

  • Dicer1 disruption accelerates lung cancer progression in a manner dependent on cell type and non-cell-autonomous signaling.
  • The developed mouse models serve as valuable tools for studying miRNA roles and intercellular communication in tumor progression.
  • Results underscore the complex, context-specific functions of miRNAs in LUAD.
Keywords:
Dicer1alveolar type 2 cellsclub cellslung cancermetastasismicroRNAsmouse modelstumor progression

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