Department of Anatomy, School of Basic Medicine, Anhui Medical University, Hefei, Anhui, 230032, China.
Department of Neurosurgery, The Fourth Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, China.
Exp Cell Res. 2022 Sep 1;418(1):113267. doi: 10.1016/j.yexcr.2022.113267. Epub 2022 Jun 22.
Glioma is the most common primary malignant intracranial tumor in the population, and is often associated with abundant angiogenesis. However, how angiogenesis is regulated during glioma progression is still poorly understood. Data mining of cancer patient database shows that MCPIP1 is positively correlated with VEGFA expression and negatively with survival. In this study, we report that overexpressed MCPIP1 in glioma cells is a boost of angiogenesis. Mechanistically, MCPIP1 upregulates the expression of VEGFA in glioma, and promote the secretion of VEGFA to the surroundings, which could stimulate angiogenesis through ERK pathway. Blocking VEGFA expression and secretion inhibited MCPIP1-mediated angiogenesis and glioma progression in vitro and xenograft models. Collectively, these results identify a critical role for MCPIP1 in angiogenesis and glioma progression by regulating the VEGFA-mediated ERK pathway, suggesting that targeting MCPIP1 may be a potential glioma-selective therapeutic strategy.
胶质瘤是人群中最常见的原发性颅内恶性肿瘤，通常与丰富的血管生成有关。然而，血管生成在胶质瘤进展过程中是如何调节的仍不清楚。对癌症患者数据库进行的数据挖掘表明，MCPIP1 与 VEGFA 的表达呈正相关，与存活率呈负相关。在这项研究中，我们报告称，在胶质瘤细胞中过表达的 MCPIP1 促进了血管生成。从机制上讲，MCPIP1 上调了胶质瘤中 VEGFA 的表达，并促进了 VEGFA 向周围环境的分泌，通过 ERK 通路刺激血管生成。阻断 VEGFA 的表达和分泌抑制了 MCPIP1 介导的体外和异种移植模型中的血管生成和胶质瘤进展。总之，这些结果表明 MCPIP1 通过调节 VEGFA 介导的 ERK 通路在血管生成和胶质瘤进展中起关键作用，表明靶向 MCPIP1 可能是一种潜在的胶质瘤选择性治疗策略。
