State Key Laboratory of Reproductive Medicine, Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Mol Cell Biochem. 2013 Jul;379(1-2):69-75. doi: 10.1007/s11010-013-1628-4. Epub 2013 Apr 17.
Epithelial-mesenchymal transition (EMT) is a crucial process that plays an important role in the invasion and metastasis of human cancers. High-mobility group AT-hook 2 (HMGA2) has been found to be involved in the EMT program, with its aberrant expression having been observed in a variety of malignant tumors. However, the mechanisms regulating HMGA2 expression remain incompletely understood. The objective of this study was to investigate whether mir-154 plays a critical role in EMT by regulating HMGA2. The expression levels of HMGA2 were examined in four samples of prostate cancer (PCa) tissue and adjacent non-tumorous tissue by Western blot analysis. The effects of forced expression of miR-154 or HMGA2 knockdown on PCa cells were evaluated by cell migration and invasion assays and Western blot analysis. HMGA2 was upregulated in the PCa tissue samples compared with the adjacent normal ones. Forced expression of miR-154 or HMGA2 knockdown significantly reduced the migratory and invasive capabilities of PCa cells in vitro and inhibited EMT gene expression, increased the levels of E-cadherin, an epithelial marker, and decreased the levels of vimentin, a mesenchymal marker. HMGA2 is a direct target gene of miR-154 by dual-luciferase reporter assay. Our findings suggest that miR-154 plays a role in regulating EMT by targeting HMGA2. Understanding the targets and regulating pathways of miR-154 may provide new insights into the underlying pathogenesis of PCa.
上皮-间质转化（EMT）是一个重要的过程，在人类癌症的侵袭和转移中起着重要作用。高迁移率族 AT 钩 2（HMGA2）已被发现参与 EMT 程序，其异常表达已在多种恶性肿瘤中观察到。然而，调节 HMGA2 表达的机制仍不完全清楚。本研究旨在探讨 mir-154 是否通过调节 HMGA2 在 EMT 中发挥关键作用。通过 Western blot 分析检测了 4 例前列腺癌（PCa）组织和相邻非肿瘤组织中 HMGA2 的表达水平。通过细胞迁移和侵袭实验以及 Western blot 分析评估了强制表达 miR-154 或 HMGA2 敲低对 PCa 细胞的影响。与相邻正常组织相比，PCa 组织样本中 HMGA2 上调。强制表达 miR-154 或 HMGA2 敲低显著降低了 PCa 细胞在体外的迁移和侵袭能力，并抑制了 EMT 基因表达，增加了上皮标志物 E-钙粘蛋白的水平，降低了间充质标志物波形蛋白的水平。双荧光素酶报告基因检测显示 HMGA2 是 miR-154 的直接靶基因。我们的研究结果表明，miR-154 通过靶向 HMGA2 在 EMT 中发挥作用。了解 miR-154 的靶标和调节途径可能为深入了解 PCa 的发病机制提供新的思路。
