RACGAP1 is transcriptionally regulated by E2F3, and its depletion leads to mitotic catastrophe in esophageal squamous cell carcinoma.

Background: 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. Methods: 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. Results: The high abnormal expression of RACGAP1 is observed in ESCC and associated with worse clinical outcomes of patients with ESCC. RACGAP1, 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. Conclusions: 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.