RP11-867G2.8 promotes EMT and chordoma malignant phenotypes by enhancing FUT4 mRNA stability and translation

Chordoma is a rare bone tumor, and the recurrence rate of chordoma is high, the treatment is difficult, and the prognosis is poor. Therefore, it is of great significance to find key target genes for the treatment of chordoma. Microarray was used to analyze the significant gene associated with chordoma. Western blot and RT-PCR were used to detect protein and mRNA expression levels of RP11-867G2.8 and FUT4. Fluorescence in situ hybridization (FISH) assay was used to locate the position of RP11-867G2.8 in chordoma cells. MTT assay, colony formation assay, transwell assay and Xenograft Mouse Model were used to clarify the function of RP11-867G2.8 and FUT4. RNA pull-down, RNA immunoprecipitation, RNA stability assay and polysome profiling analysis were used to clarify the relationship between RP11-867G2.8 and FUT4. We found that RP11-867G2.8 is highly expressed in chordoma tissues and cells, and RP11-867G2.8 overexpression promotes the malignant biological behavior of chordoma cells. RP11-867G2.8 overexpression alters the expression pattern of genes modulating signaling pathway. FUT4 is accumulated in chordoma tissues, and RP11-867G2.8 is antisense RNA of FUT4. RP11-867G2.8 can bind to FUT4 mRNA, increasing FUT4 mRNA stability and facilitating translation of FUT4. RP11-867G2.8 binds to EIF4B and PABPC1, which increases the translation of FUT4. Further studies found that FUT4 silence counteracts the effect of RP11-867G2.8 in vivo and in vitro. Our results suggest that RP11-867G2.8 promotes the development and progression of chordoma by up-regulating the expression of FUT4.