Muscle-invasive or metastatic bladder cancer (BCa) is a life-threatening disease for patients, and tumor angiogenesis is believed to play a critical role in the progression of BCa. However, its underlying mechanism of tumor angiogenesis is still poorly understood. In this study, we discovered that RASAL2, a RAS GTPase activating protein, could inhibit BCa angiogenesis based on our shRNA/siRNA knockdown or ectopic cDNA expression experiments. Mechanistically, RASAL2 downregulation could enhance the phosphorylation of AKT and then subsequently upregulate the expression of ETS1 and VEGFA. Furthermore, there was a negative correlation between RASAL2 and VEGFA or CD31 expression in subcutaneous xenograft and human BCa specimens. Taken together, we provide a new insight into the molecular mechanism of BCa progression, in which RASAL2 can be a new therapeutic target.

肌肉浸润性或转移性膀胱癌（BCa）对患者来说是威胁生命的疾病，并且肿瘤血管生成被认为在BCa的进展中起着至关重要的作用。然而，其肿瘤血管生成的潜在机制仍知之甚少。在这项研究中，我们发现基于我们的shRNA / siRNA抑制或异位cDNA表达实验，RAS GTPase活化蛋白RASAL2可以抑制BCa血管生成。从机制上讲，RASAL2下调可以增强AKT的磷酸化，然后上调ETS1和VEGFA的表达。此外，皮下异种移植和人BCa标本中RASAL2与VEGFA或CD31表达之间呈负相关。综上所述，我们为BCa进程的分子机制提供了新的见解，