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Updated: Jul 6, 2026
In Vivo Inhibition of MicroRNA to Decrease Tumor Growth in Mice
Published on: August 23, 2019
The let-7 microRNA reduces tumor growth in mouse models of lung cancer
Aurora Esquela-Kerscher1, Phong Trang, Jason F Wiggins
1Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, Connecticut 06520, USA.
Abstract:
MicroRNAs have been increasingly implicated in human cancer and interest has grown about the potential to use microRNAs to combat cancer. Lung cancer is the most prevalent form of cancer worldwide and lacks effective therapies. Here we have used both in vitro and in vivo approaches to show that the let-7 microRNA directly represses cancer growth in the lung. We find that let-7 inhibits the growth of multiple human lung cancer cell lines in culture, as well as the growth of lung cancer cell xenografts in immunodeficient mice. Using an established orthotopic mouse lung cancer model, we show that intranasal let-7 administration reduces tumor formation in vivo in the lungs of animals expressing a G12D activating mutation for the K-ras oncogene. These findings provide direct evidence that let-7 acts as a tumor suppressor gene in the lung and indicate that this miRNA may be useful as a novel therapeutic agent in lung cancer.
Insights
The let-7 microRNA suppresses lung cancer growth. Intranasal administration of let-7 reduced tumor formation in mice, suggesting its potential as a novel lung cancer therapy.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- MicroRNAs are increasingly recognized for their roles in human cancer development.
- Lung cancer remains a leading cause of cancer mortality with limited effective therapeutic options.
- The potential of microRNAs as therapeutic agents for cancer is an area of active research.
Purpose of the Study:
- To investigate the role of the let-7 microRNA in regulating lung cancer growth.
- To determine if let-7 functions as a tumor suppressor in the lung.
- To evaluate the therapeutic potential of let-7 for lung cancer treatment.
Main Methods:
- In vitro studies using human lung cancer cell lines.
- In vivo studies involving lung cancer cell xenografts in immunodeficient mice.
- An orthotopic mouse lung cancer model with intranasal administration of let-7.
Main Results:
- let-7 inhibited the proliferation of multiple human lung cancer cell lines in culture.
- let-7 suppressed the growth of lung cancer cell xenografts in mice.
- Intranasal administration of let-7 reduced tumor formation in a mouse model of lung cancer with K-ras mutations.
Conclusions:
- let-7 acts as a direct tumor suppressor in lung cancer.
- let-7 demonstrates potential as a novel therapeutic agent for lung cancer.
- Targeting let-7 pathways may offer a new strategy for lung cancer treatment.
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