1. Academic Validation
  2. MiR-206 promotes extracellular matrix accumulation and relieves infantile hemangioma through targeted inhibition of DNMT3A

MiR-206 promotes extracellular matrix accumulation and relieves infantile hemangioma through targeted inhibition of DNMT3A

  • Cell Cycle. 2021 May;20(10):978-992. doi: 10.1080/15384101.2021.1919820.
Minliang Wu 1 Yong Chen 2 Ling Feng 3 Haiying Dai 1 Shuo Fang 1 Jianguo Xu 1
Affiliations

Affiliations

  • 1 Department of Plastic Surgery, Changhai Hospital, Naval Medical University, Shanghai, China.
  • 2 Department of Plastic Surgery, School of Medicine, Jinling Hospital, Nanjing University, Nanjing, Jiangsu, China.
  • 3 Department of Pharmacy, Changhai Hospital, Naval Medical University, Shanghai, China.
Abstract

MiR-206 is abnormally expressed in infant hemangioma endothelial cells (HemECs), but the mechanism is not clear. We explored the intervention of miR-206 in HemECs in relation to extracellular matrix (ECM) metabolism. We selected 48 cases of infantile hemangioma (IH) from volunteer organizations. After the isolated and extracted HemECs were interfered with overexpressed or silenced miR-206, the effects of miR-206 on the proliferation, migration and invasion of HemECs were examined through basic cell function experiments. The expression differences of miR-206, DNA Methyltransferase 3A (DNMT3A) and ECM-related genes were analyzed as needed by qRT-PCR or Western blot. TargetScan and dual-luciferase experiments were applied to predict and confirm the binding relationship between miR-206 and DNMT3A. The correlation between miR-206 and DNMT3A was analyzed in IH tissues by Pearson correlation coefficient, and further confirmed in HemECs by conducting rescue experiments. A nude mouse model of xenograft tumor was constructed to verify the results of in vitro experiments. MiR-206, which was downregulated in proliferative hemangioma, suppressed the malignant development of HemECs by regulating ECM-related genes. As the target gene of miR-206, DNMT3A was high-expressed in IH tissues and was negatively correlated with miR-206. Overexpressed DNMT3A counteracted the inhibitory effect of miR-206 mimic on HemECs and its regulatory effect on ECM. The results of in vivo experiments were consistent with those from cell experiments. Thus, miR-206 could promote ECM accumulation through targeted inhibition of DNMT3A, further inhibiting the malignant development of HemECs and relieving IH.

Keywords

DNA methyltransferase 3A; Infantile hemangioma; extracellular matrix; hemangioma endothelial cells; miR-206.

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