Wang Qiong, Wang Guanwen, Niu Lianjie, Zhao Shaorong, Li Jianjun, Zhang Zhen, Jiang Huimin, Zhang Quansheng, Wang Hang, Sun Peiqing, Xiang Rong, Chang Antao, Yang Shuang
Tianjin Key Laboratory of Tumor Microenvironment and Neurovascular Regulation, Medical College of Nankai University, Tianjin 300071, China.
Tianjin Medical University, Tianjin 300070, China.
J Oncol. 2021 Jan 29;2021:6617700. doi: 10.1155/2021/6617700. eCollection 2021.
Hepatocellular carcinoma (HCC), the most common primary liver cancer, relies on the formation of new blood vessel for growth and frequent intrahepatic and extrahepatic metastasis. Therefore, it is important to explore the underlying molecular mechanisms of tumor angiogenesis of HCC. Recently, microRNAs have been shown to modulate angiogenic processes by modulating the expression of critical angiogenic factors. However, the potential roles of tumor-derived exosomal microRNAs in regulating tumor angiogenesis remain to be elucidated. In this study, our miRNome sequencing demonstrated that miR-1290 was overexpressed in HCC patient serum-derived exosomes, and we found that delivery of miR-1290 into human endothelial cells enhanced their angiogenic ability. Our results further revealed that SMEK1 is a direct target of miR-1290 in endothelial cells. MiR-1290 exerted its proangiogenic function, at least in part, by alleviating the inhibition of VEGFR2 phosphorylation done by SMEK1. Collectively, our findings provide evidence that miR-1290 is overexpressed in HCC and promotes tumor angiogenesis via exosomal secretion, implicating its potential role as a therapeutic target for HCC.
肝细胞癌（HCC）是最常见的原发性肝癌，其生长依赖于新血管的形成，并常发生肝内和肝外转移。因此，探索HCC肿瘤血管生成的潜在分子机制具有重要意义。最近研究表明，微小RNA（microRNAs）可通过调节关键血管生成因子的表达来调控血管生成过程。然而，肿瘤来源的外泌体微小RNA在调节肿瘤血管生成中的潜在作用仍有待阐明。在本研究中，我们的微小RNA组测序显示，miR-1290在HCC患者血清来源的外泌体中过表达，并且我们发现将miR-1290导入人内皮细胞可增强其血管生成能力。我们的结果进一步揭示，SMEK1是内皮细胞中miR-1290的直接靶点。miR-1290至少部分地通过减轻SMEK1对VEGFR2磷酸化的抑制作用来发挥其促血管生成功能。总的来说，我们的研究结果表明，miR-1290在HCC中过表达，并通过外泌体分泌促进肿瘤血管生成，提示其作为HCC治疗靶点的潜在作用。
