Zhao Weifeng, Wang Mengyao, Wang Chaojie, Liu Yingjun, Liu Huimin, Luo Suxia
Department of Medical Oncology, the Affiliated Tumor Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, China.
Department of Oncology, People's Hospital of Zhengzhou University, Henan Provincial People's Hospital, Zhengzhou, China.
Ann Transl Med. 2020 Aug;8(15):950. doi: 10.21037/atm-20-2901.
RACGAP1 has significant involvement in tumorigenesis of cancers, including liver cancer, stomach cancer, and colon cancer. However, the role and the exact mechanism of RACGAP1 in esophageal squamous cell carcinoma (ESCC) has not been explored.
QPCR and Western blots analysis was performed to analyze the expression of RACGAP1 in ESCC. MTT assays and colony formation assays were performed to explore the functional role of RACGAP1 in ESCC. Cell cycle analysis and immunofluorescence assays were used to investigate the function of RACGAP1 involvement in mitotic catastrophe. At last, we conducted the public datasets mining to explore the expression status and prognosis value of RACGAP1 as well as the correlation between RACGAP1 and E2F3 in various cancers.
The high abnormal expression of RACGAP1 is observed in ESCC and associated with worse clinical outcomes of patients with ESCC. , a novel cell cycle associated gene regulated by E2F3, acts as an oncogenic driver in ESCC cell lines. Notably, for the first time, RACGAP1 depletion induced severe mitotic catastrophe, followed by massive cell death.
Our findings showed the essential role of RACGAP1 in ESCC cancer cell survival and the therapeutic potential of RACGAP1 as a molecular target for ESCC.
RACGAP1在包括肝癌、胃癌和结肠癌在内的多种癌症的肿瘤发生过程中发挥着重要作用。然而，RACGAP1在食管鳞状细胞癌（ESCC）中的作用及确切机制尚未得到研究。
采用QPCR和蛋白质免疫印迹分析来检测RACGAP1在ESCC中的表达。通过MTT法和集落形成试验来探究RACGAP1在ESCC中的功能作用。利用细胞周期分析和免疫荧光试验来研究RACGAP1参与有丝分裂灾难的功能。最后，我们进行了公共数据集挖掘，以探究RACGAP1在各种癌症中的表达状态、预后价值以及RACGAP1与E2F3之间的相关性。
在ESCC中观察到RACGAP1高度异常表达，且与ESCC患者较差的临床预后相关。RACGAP1是一种受E2F3调控的新型细胞周期相关基因，在ESCC细胞系中作为致癌驱动因子发挥作用。值得注意的是，首次发现RACGAP1缺失会引发严重的有丝分裂灾难，随后导致大量细胞死亡。
我们的研究结果表明RACGAP1在ESCC癌细胞存活中起着至关重要的作用，并且RACGAP1作为ESCC的分子靶点具有治疗潜力。
