CRISPR/Cas9-based genome-wide screening for Metastasis ability identifies FCGR1A regulating the metastatic process of ovarian cancer by targeting LSP1

Abstract

Abstract Background: Metastasis is a main cause of death from ovarian cancer(OC). Screening key makers involved in OC metastasis can help to effectively detect early metastasis postoperatively. However, the role of FCGR1A involved in OC metastasis has yet to be fully established. Methods: A genome-wide CRISPR/Cas9-based screening system was used to identify regulatory factor in metastasis. Expression of FCGR1A and LSP1 in the ovarian cancer cell lines was examined by quantitative real-time polymerase chain reaction (qRT-PCR).The functions of FCGR1A and LSP1 in OC cell migration, invasion and proliferation were determined using wound healing assay, transwell invasion assay and CKK8 assay. A transcription-activated library was used to identify the potential downstream gene of FCGR1A. FCGR1A expression was immunohistochemically detected and IRS scores were calculated. Results: FCGR1A was upregulated in OC cells compared with normal ovarian cell. Downregulation of FCGR1A inhibited the metastasis, proliferation and EMT progression in OC cells in vitro and intraperitoneal metastasis in vivo.Moreover, Downregulation of FCGR1A accompanied with lower LSP1 expression. Overexpression of LSP1 partially reversed the tumor suppressive function caused by FCGR1A Downregulation. The higher FCGR1A expression level was related to metastasis, higher grade, higher stage, and lymph node metastasis of OC. Survival analysis suggested that the group with higher FCGR1A expression had a lower tumor-free survival rate and a lower overall survival rate than the group with low FCGR1A expression. Conclusion: FCGR1Aenhances OC metastasis by regulating LSP1 and that FCGR1A is associated with poor prognosis, supporting FCGR1A as a potential predictive factor for detecting early metastasis postoperatively.