BACKGROUND: Our previous study showed that guanine nucleotide exchange factor T (GEFT) was highly expressed in colorectal cancer (CRC) tissues and CRC patients with high GEFT expression had a poor prognosis, and suggested the close link of GEFT expression and CRC tumorigenesis/metastasis. In this text, the roles and upstream regulatory mechanisms of GEFT in the development and progression of CRC were further investigated. METHODS: Expression levels of GEFT mRNA and LINC00355 was measured by RT-qPCR assay. Protein levels of lin-28 homologue A (LIN28A) and GEFT were determined by western blot assay. Cell proliferative, migratory, and invasive capacities were assessed by CCK-8, Transwell migration and invasion assays, respectively. The effect of GEFT knockdown on CRC tumorigenesis was examined by mouse xenograft experiments in vivo. GEFT mRNA stability was examined by actinomycin D assay. The relationships of LINC000355, LIN28A, and GEFT were explored by RNA pull down and RIP assays. RESULTS: GEFT was highly expressed in CRC tissues and cell lines. GEFT knockdown inhibited CRC cell proliferation, migration, and invasion, and hindered CRC xenograft tumor growth. GEFT overexpression alleviated the detrimental effects of LINC00355 loss on CRC cell proliferation, migration, and invasion. LINC00355 promoted GEFT expression and enhanced GEFT mRNA stability via LIN28A. LIN28A knockdown weakened the promotive effect of LINC00355 on CRC cell proliferation, migration, and invasion. CONCLUSION: LINC00355 facilitated CRC tumorigenesis and progression by increasing GEFT expression via LIN28A, deepening our understanding on roles and upstream regulatory mechanisms of GEFT in CRC development and progression.
BACKGROUND: Our previous study showed that guanine nucleotide exchange factor T (GEFT) was highly expressed in colorectal cancer (CRC) tissues and CRC patients with high GEFT expression had a poor prognosis, and suggested the close link of GEFT expression and CRC tumorigenesis/metastasis. In this text, the roles and upstream regulatory mechanisms of GEFT in the development and progression of CRC were further investigated. METHODS: Expression levels of GEFT mRNA and LINC00355 was measured by RT-qPCR assay. Protein levels of lin-28 homologue A (LIN28A) and GEFT were determined by western blot assay. Cell proliferative, migratory, and invasive capacities were assessed by CCK-8, Transwell migration and invasion assays, respectively. The effect of GEFT knockdown on CRC tumorigenesis was examined by mouse xenograft experiments in vivo. GEFT mRNA stability was examined by actinomycin D assay. The relationships of LINC000355, LIN28A, and GEFT were explored by RNA pull down and RIP assays. RESULTS: GEFT was highly expressed in CRC tissues and cell lines. GEFT knockdown inhibited CRC cell proliferation, migration, and invasion, and hindered CRC xenograft tumor growth. GEFT overexpression alleviated the detrimental effects of LINC00355 loss on CRC cell proliferation, migration, and invasion. LINC00355 promoted GEFT expression and enhanced GEFT mRNA stability via LIN28A. LIN28A knockdown weakened the promotive effect of LINC00355 on CRC cell proliferation, migration, and invasion. CONCLUSION: LINC00355 facilitated CRC tumorigenesis and progression by increasing GEFT expression via LIN28A, deepening our understanding on roles and upstream regulatory mechanisms of GEFT in CRC development and progression.