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Updated: Jun 11, 2026

In Vivo Inhibition of MicroRNA to Decrease Tumor Growth in Mice
Published on: August 23, 2019
A MicroRNA targeting dicer for metastasis control
Graziano Martello1, Antonio Rosato, Francesco Ferrari
1Department of Histology, Microbiology and Medical Biotechnologies, University of Padua School of Medicine, viale Colombo 3, 35126 Padua, Italy.
Abstract:
Although specific microRNAs (miRNAs) can be upregulated in cancer, global miRNA downregulation is a common trait of human malignancies. The mechanisms of this phenomenon and the advantages it affords remain poorly understood. Here we identify a microRNA family, miR-103/107, that attenuates miRNA biosynthesis by targeting Dicer, a key component of the miRNA processing machinery. In human breast cancer, high levels of miR-103/107 are associated with metastasis and poor outcome. Functionally, miR-103/107 confer migratory capacities in vitro and empower metastatic dissemination of otherwise nonaggressive cells in vivo. Inhibition of miR-103/107 opposes migration and metastasis of malignant cells. At the cellular level, a key event fostered by miR-103/107 is induction of epithelial-to-mesenchymal transition (EMT), attained by downregulating miR-200 levels. These findings suggest a new pathway by which Dicer inhibition drifts epithelial cancer toward a less-differentiated, mesenchymal fate to foster metastasis.
Insights
High levels of microRNAs (miRNAs), specifically miR-103/107, promote cancer metastasis by targeting Dicer and inducing epithelial-to-mesenchymal transition (EMT). Inhibiting these miRNAs can reduce cancer cell migration and spread.
Area of Science:
- Molecular Biology
- Oncology
- Gene Regulation
Background:
- Global microRNA (miRNA) downregulation is common in human cancers, but its mechanisms and benefits are unclear.
- MicroRNAs regulate gene expression and are crucial in cancer development and progression.
Purpose of the Study:
- To identify miRNAs involved in global miRNA downregulation in cancer.
- To investigate the role of miR-103/107 in cancer metastasis and epithelial-to-mesenchymal transition (EMT).
Main Methods:
- Identification of miR-103/107 targeting Dicer, a key enzyme in miRNA biosynthesis.
- Analysis of miR-103/107 levels in human breast cancer tissues.
- In vitro and in vivo experiments to assess the functional impact of miR-103/107 on cell migration and metastasis.
- Investigation of miR-103/107's effect on miR-200 levels and EMT induction.
Main Results:
- miR-103/107 directly target and attenuate Dicer, reducing overall miRNA biosynthesis.
- Elevated miR-103/107 levels correlate with metastasis and poor prognosis in breast cancer patients.
- Overexpression of miR-103/107 enhances cancer cell migration in vitro and promotes metastasis in vivo.
- Inhibition of miR-103/107 suppresses cancer cell migration and metastasis.
- miR-103/107 induce EMT by downregulating miR-200 family members.
Conclusions:
- The miR-103/107 family plays a critical role in promoting cancer metastasis through Dicer inhibition and EMT induction.
- Targeting miR-103/107 offers a potential therapeutic strategy to combat cancer metastasis.
- This study reveals a novel mechanism linking miRNA dysregulation to cancer progression and invasiveness.
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