Article

Down-Regulation of mir-424 Contributes to the Abnormal Angiogenesis via MEK1 and Cyclin E1 in Senile Hemangioma: Its Implications to Therapy

Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
PLoS ONE (Impact Factor: 3.53). 12/2010; 5(12):e14334. DOI: 10.1371/journal.pone.0014334
Source: PubMed

ABSTRACT Senile hemangioma, so-called cherry angioma, is known as the most common vascular anomalies specifically seen in the aged skin. The pathogenesis of its abnormal angiogenesis is still unclear.
In this study, we found that senile hemangioma consisted of clusters of proliferated small vascular channels in upper dermis, indicating that this tumor is categorized as a vascular tumor. We then investigated the mechanism of endothelial proliferation in senile hemangioma, focusing on microRNA (miRNA). miRNA PCR array analysis revealed the mir-424 level in senile hemangioma was lower than in other vascular anomalies. Protein expression of MEK1 and cyclin E1, the predicted target genes of mir-424, was increased in senile hemangioma compared to normal skin or other anomalies, but their mRNA levels were not. The inhibition of mir-424 in normal human dermal microvascular ECs (HDMECs) using specific inhibitor in vitro resulted in the increase of protein expression of MEK1 or cyclin E1, while mRNA levels were not affected by the inhibitor. Specific inhibitor of mir-424 also induced the cell proliferation of HDMECs significantly, while the cell number was decreased by the transfection of siRNA for MEK1 or cyclin E1.
Taken together, decreased mir-424 expression and increased levels of MEK1 or cyclin E1 in senile hemangioma may cause abnormal cell proliferation in the tumor. Senile hemangioma may be the good model for cutaneous angiogenesis. Investigation of senile hemangioma and the regulatory mechanisms of angiogenesis by miRNA in the aged skin may lead to new treatments using miRNA by the transfection into senile hemangioma.

0 Followers
 · 
106 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: The thyroid hormone receptors (TRs) mediate tumor suppressive effects in hepatocarcinoma and breast cancer cells. Here we show that incubation of hepatocarcinoma SK-hep1 cells expressing TRb with the thyroid hormone T3 induces transcription of the polycistronic message coding for microRNAs 424 and 503. TRb binds to the promoter region of these miRNAs and T3 induces an exchange of corepressors and coactivators inducing histone acetylation and transcriptional stimulation. We have validated cell cycle components as targets of these miRNAs. Overexpression of miR-424 mimicked the repressive effect of T3 on cell proliferation, growth in suspension, migration and invasion. Knockdown of miR-424 or miR-503 reduced the inhibitory effect of the hormone. T3 increased miR-424 and miR-503 in breast cancer cells expressing TRb, and this induction is also involved in the anti-invasive effects of the hormone. Furthermore, miR-424 or miR-503 depletion enhanced extravasation to the lungs of hepatocarcinoma cells injected in the tail vein of mice. The levels of these miRNAs were reduced in xenograft tumors formed in hypothyroid nude mice that are more invasive. Therefore, miR-424 or miR-503 mediate anti-proliferative and anti-invasive actions of TRb both in cultured cells and in vivo.
    Oncotarget 04/2014; 5(10). · 6.63 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Pulmonary arterial hypertension (PAH) is a devastating disease without effective treatment. Despite decades of research and development of novel treatments, PAH remains a fatal disease, suggesting an urgent need for better understanding of the pathogenesis of PAH. Recent studies suggest that microRNAs (miRNAs) are dysregulated in patients with PAH and in experimental pulmonary hypertension. Furthermore, normalization of a few miRNAs is reported to inhibit experimental pulmonary hypertension. We have reviewed the current knowledge about miRNA biogenesis, miRNA expression pattern, and their roles in regulation of pulmonary artery smooth muscle cells, endothelial cells, and fibroblasts. We have also identified emerging trends in our understanding of the role of miRNAs in the pathogenesis of PAH and propose future studies that might lead to novel therapeutic strategies for the treatment of PAH.
    American Journal of Respiratory Cell and Molecular Biology 09/2014; DOI:10.1165/rcmb.2014-0166TR · 4.11 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: MicroRNA-34 is involved in pathogenesis in cancer by targeting different tumor-related genes. It could be a biomarker for predicting the prognosis of patients with cancer. In addition, miR-34 is involved in the tumor angiogenesis. Understanding the mechanism of the miR-34 in cancer and tumor angiogenesis will open horizons for development of anti-cancer and anti-angiogenesis drugs.
    Experimental and Molecular Pathology 08/2014; DOI:10.1016/j.yexmp.2014.08.002 · 2.88 Impact Factor

Full-text (4 Sources)

Download
29 Downloads
Available from
May 31, 2014