Journal
JOURNAL OF INVESTIGATIVE DERMATOLOGY
Volume 136, Issue 12, Pages 2485-2494Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jid.2016.06.630
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Funding
- Swedish Research Council [VR 2015-02844]
- Swedish Cancer Society [CAN 2012/730, CAN 2015/694]
- Swedish Society of Medicine (Svenska Lakaresallskapet)
- European Skin Research Foundation
- Welander and Finsens Foundation
- Tore Nilssons Foundation
- Lars Hierta Memorial Foundation
- Sigurd and Elsa Golje Memorial Foundation
- Stockholm County Council
- Finnish Cancer Research Foundation
- Sigrid Juselius Foundation
- Turku University Hospital EVO [13336]
- Cancer Foundation Finland sr [140127] Funding Source: researchfish
- Swedish Research Council [2015-02844] Funding Source: Swedish Research Council
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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-203einduced growth arrest in cSCC, which highlights the importance of c-MYC within the miR-203eregulated 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.
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