Department of cell Biology and Genetics, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, China.
Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, China.
Sci Rep. 2018 Feb 5;8(1):2431. doi: 10.1038/s41598-018-20859-3.
Hepatocellular carcinoma (HCC), one of the most common aggressive tumors worldwide has a relatively high mortality rate among malignant tumors. MicroRNAs (miRNAs), acting as tumor suppressors, are involved in the regulation of invasion, metastasis, and angiogenesis of tumor cells. However, a potential role for miR-203a in HCC has not been described yet. In this study, we show that miR-203a markedly suppresses HCC cell migration, invasion, and angiogenesis. In addition, the transcription factor HOXD3 appears to be a direct target of miR-203a. HOXD3 knockdown substantially decreased HCC cell migration, invasion, and angiogenesis, effects similar to those seen for miR-203a expression. Rescuing the function of HOXD3 attenuated the effect of miR-203a overexpression in HCC cells. Furthermore, HOXD3 can directly target the promoter region of VEGFR and increase VEGFR expression. Taken together, our findings indicate that miR-203a inhibits HCC cell invasion, metastasis, and angiogenesis by negatively targeting HOXD3 and suppressing cell signaling through the VEGFR pathway, suggesting that miR-203a might represent a potential therapeutic target for HCC intervention.
肝细胞癌 (HCC) 是全球最常见的侵袭性肿瘤之一，其恶性肿瘤死亡率相对较高。微 RNA（miRNA）作为肿瘤抑制因子，参与肿瘤细胞的侵袭、转移和血管生成的调节。然而，miR-203a 在 HCC 中的潜在作用尚未被描述。在这项研究中，我们表明 miR-203a 显著抑制 HCC 细胞的迁移、侵袭和血管生成。此外，转录因子 HOXD3 似乎是 miR-203a 的直接靶标。HOXD3 敲低显著降低 HCC 细胞的迁移、侵袭和血管生成，其作用与 miR-203a 表达相似。挽救 HOXD3 的功能减弱了 miR-203a 在 HCC 细胞中的过表达效应。此外，HOXD3 可以直接靶向 VEGFR 的启动子区域并增加 VEGFR 的表达。综上所述，我们的研究结果表明，miR-203a 通过负向靶向 HOXD3 并通过 VEGFR 途径抑制细胞信号传导来抑制 HCC 细胞的侵袭、转移和血管生成，提示 miR-203a 可能成为 HCC 干预的潜在治疗靶点。
