Department of Plastic Surgery, Changhai Hospital, Naval Medical University, Shanghai, China.
Department of Plastic Surgery, School of Medicine, Jinling Hospital, Nanjing University, Nanjing, Jiangsu, China.
Cell Cycle. 2021 May;20(10):978-992. doi: 10.1080/15384101.2021.1919820. Epub 2021 May 4.
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 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 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.
miR-206 在婴儿血管瘤内皮细胞（HemECs）中异常表达，但机制尚不清楚。我们探讨了 miR-206 对 HemECs 细胞外基质（ECM）代谢的干预作用。我们从志愿者组织中选择了 48 例婴儿血管瘤（IH）。在对分离和提取的 HemECs 进行过表达或沉默 miR-206 干预后，通过基础细胞功能实验检测 miR-206 对 HemECs 增殖、迁移和侵袭的影响。根据需要通过 qRT-PCR 或 Western blot 分析 miR-206、DNA 甲基转移酶 3A（DNMT3A）和 ECM 相关基因的表达差异。应用靶标扫描和双荧光素酶实验预测和确认 miR-206 和 DNMT3A 之间的结合关系。通过 Pearson 相关系数分析 IH 组织中 miR-206 与 DNMT3A 的相关性，并在 HemECs 中通过进行挽救实验进一步验证。构建裸鼠异种移植瘤模型验证实验结果。在增生性血管瘤中下调的 miR-206 通过调节 ECM 相关基因抑制 HemECs 的恶性发展。作为 miR-206 的靶基因，DNMT3A 在 IH 组织中高表达，与 miR-206 呈负相关。过表达的 DNMT3A 抵消了 miR-206 模拟物对 HemECs 的抑制作用及其对 ECM 的调节作用。实验结果与细胞实验结果一致。因此，miR-206 可以通过靶向抑制 DNMT3A 促进 ECM 积累，进一步抑制 HemECs 的恶性发展，缓解 IH。
