LncRNA AK093407-IFITM1- Wnt/β-catenin regulation axis in colorectal cancer

ObjectiveColorectal cancer (CRC) carries high morbidity and mortality worldwide. IFITM1 serves as a potential independent prognostic factor for CRC metastasis and advanced stages, partly through regulating the Wnt/β-catenin pathway. LncRNA AK093407 is upregulated in CRC and promotes cancer cell proliferation, but its regulatory mechanism remains unclear. This study aimed to investigate the biological function of LncRNA AK093407 in CRC progression and clarify its regulatory mechanism on IFITM1 and the Wnt/β-catenin signaling pathway.MethodsThis in vitro study included clinical tissue samples from 22 CRC patients and human CRC cell lines. Proteomic analysis was applied to screen potential downstream targets of AK093407. The expression levels of AK093407 and IFITM1 in clinical tissues and cell lines were detected by qRT-PCR. Lentiviral infection and siRNA transfection were used to establish overexpression and knockdown models. MTT, colony formation, transwell, wound healing, and flow cytometry assays were performed to assess cell proliferation, migration, invasion, and apoptosis. Western blotting was used to measure key proteins in the Wnt/β-catenin pathway. Subcellular fractionation and RIP assays were used to explore the molecular mechanism.ResultsLncRNA AK093407 and IFITM1 were both significantly highly expressed in CRC tissues and cells. Overexpression of AK093407 or IFITM1 markedly enhanced proliferation, migration, and invasion and inhibited apoptosis. Knockdown of IFITM1 reversed the oncogenic effects induced by AK093407 overexpression, while IFITM1 overexpression rescued the phenotypic changes caused by AK093407 silencing. Mechanistically, IFITM1 activated the Wnt/β-catenin pathway and directly interacted with β-catenin.ConclusionsLncRNA AK093407 promotes CRC malignant progression by upregulating IFITM1 and activating the Wnt/β-catenin signaling pathway, forming a novel AK093407-IFITM1-Wnt/β-catenin regulatory axis. These findings identify a potential diagnostic and therapeutic target for CRC, although further in vivo validation is warranted.