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Updated: Mar 17, 2026

Genome-wide Screen for miRNA Targets Using the MISSION Target ID Library
Published on: April 6, 2012
MicroRNA-203 Inversely Correlates with Differentiation Grade, Targets c-MYC, and Functions as a Tumor Suppressor in
Warangkana Lohcharoenkal1, Masako Harada2, Jakob Lovén3
1Unit of Dermatology and Venereology, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
Abstract:
Cutaneous squamous cell carcinoma (cSCC) is the second most common cancer and a leading cause of cancer mortality among solid organ transplant recipients. MicroRNAs (miR) are short RNAs that regulate gene expression and cellular functions. Here, we show a negative correlation between miR-203 expression and the differentiation grade of cSCC. Functionally, miR-203 suppressed cell proliferation, cell motility, and the angiogenesis-inducing capacity of cSCC cells in vitro and reduced xenograft tumor volume and angiogenesis in vivo. Transcriptomic analysis of cSCC cells with ectopic overexpression of miR-203 showed dramatic changes in gene networks related to cell cycle and proliferation. Transcription factor enrichment analysis identified c-MYC as a hub of miR-203-induced transcriptomic changes in squamous cell carcinoma. We identified c-MYC as a direct target of miR-203. Overexpression of c-MYC in rescue experiments reversed miR-203-induced growth arrest in cSCC, which highlights the importance of c-MYC within the miR-203-regulated gene network. Together, miR-203 acts as a tumor suppressor in cSCC, and its low expression can be a marker for poorly differentiated tumors. Restoration of miR-203 expression may provide a therapeutic benefit, particularly in poorly differentiated cSCC.
Insights
MicroRNA-203 (miR-203) acts as a tumor suppressor in cutaneous squamous cell carcinoma (cSCC). Low miR-203 expression correlates with poor differentiation and can be targeted for therapeutic benefit in cSCC.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Cutaneous squamous cell carcinoma (cSCC) is a significant cause of mortality in organ transplant recipients.
- MicroRNAs (miRs) are key regulators of gene expression and cellular processes.
- The role of miR-203 in cSCC pathogenesis remains incompletely understood.
Purpose of the Study:
- To investigate the function of miR-203 in cSCC.
- To determine the correlation between miR-203 expression and cSCC differentiation.
- To identify molecular targets and pathways regulated by miR-203 in cSCC.
Main Methods:
- Correlation analysis of miR-203 expression and cSCC differentiation grade.
- In vitro assays assessing cell proliferation, motility, and angiogenesis.
- In vivo xenograft studies to evaluate tumor growth and angiogenesis.
- Transcriptomic and transcription factor enrichment analyses.
- Luciferase reporter assays to validate miR-203 target interactions.
Main Results:
- A negative correlation was observed between miR-203 expression and cSCC differentiation grade.
- miR-203 suppressed cSCC cell proliferation, motility, and angiogenesis in vitro and tumor growth in vivo.
- Transcriptomic analysis revealed miR-203 regulates cell cycle and proliferation networks.
- c-MYC was identified as a direct target of miR-203 and a key mediator of its tumor-suppressive effects.
Conclusions:
- miR-203 functions as a tumor suppressor in cSCC.
- Reduced miR-203 expression is associated with poorly differentiated cSCC.
- miR-203 targeting of c-MYC is crucial for its anti-tumor activity.
- Restoring miR-203 expression holds therapeutic potential for cSCC, especially poorly differentiated types.
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