LncRNA FOXP4-AS1 facilitates colorectal cancer invasion and migration by enhancing USP7 interaction with ZEB1 Running title: LncRNA FOXP4-AS1 raises CRC invasion and migration

Colorectal cancer (CRC) poses a threat to the health of people worldwide. Long noncoding RNAs (lncRNAs) have been reported to play a key role in regulating carcinogenesis, including CRC. In this study, the levels of lncRNA forkhead box P4 antisense RNA 1 (FOXP4-AS1) were analyzed in CRC cell lines and normal cell lines using quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) method. The effects of FOXP4-AS1 on CRC cell metastasis were investigated. Then, the silver staining assay, western blot, RIP, Co-IP, and immunofluorescence were used to explore and validate the molecular mechanisms by which FOXP4-AS1 affects CRC progression. We discovered that FOXP4-AS1 expression was significantly elevated in CRC tissues and cell lines. Functionally, knockdown of FOXP4-AS1 expression inhibited CRC cell migration and invasion. In addition, silencing FOXP4-AS1 weakened CRC tumor growth in vivo . Mechanistically, we identified that FOXP4-AS1 enhanced the interaction of USP7 with ZEB1. Rescue experiments demonstrated that USP7 inhibitor P005091 rescued the promotion of cell migration, invasion and EMT by overexpression of FOXP4-AS1. Furthermore, ZEB1 overexpression reversed the impact of silencing FOXP4-AS1 on cell migration, invasion and EMT. LncRNA FOXP4-AS1 accelerates CRC malignant progression by strengthening the interaction between USP7 and ZEB1.