Details

Autor(en) / Beteiligte

• Lohcharoenkal, Warangkana
• Harada, Masako
• Lovén, Jakob
• Meisgen, Florian
• Landén, Ning Xu
• Zhang, Lingyun
• Lapins, Jan
• Mahapatra, Kunal Das
• Shi, Hao
• Nissinen, Liisa
• Kähäri, Veli-Matti
• Ståhle, Mona
• Sonkoly, Enikö
• Grandér, Dan
• Arsenian-Henriksson, Marie
• Pivarcsi, Andor

Titel

MicroRNA-203 Inversely Correlates with Differentiation Grade, Targets c-MYC, and Functions as a Tumor Suppressor in cSCC

Ist Teil von

• Journal of investigative dermatology, 2016-12, Vol.136 (12), p.2485-2494

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2016

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.