Effect Of RBM17 Knockdown On Cisplatin Sensitivity,Migration,Invasion And EMT In Hypopharyngeal Carcinoma

Objectives: The aim of this study was to investigate the effect and mechanism of RNA-binding motif protein 17(RBM17)on cisplatin sensitivity,migration,invasion and epithelial-mesenchymal transition(EMT)in hypopharyngeal squamous cell carcinoma(HSCC).Methods: The expression of RMB17 in cancer tissues and its relationship with prognosis were analyzed based on GEPIA and UALCAN data platforms.Collect hypopharyngeal cancer tissues and normal tissues adjacent to the cancer,and verify the expression level of RBM17 in the tissue specimens.The expression levels of RBM17 in hypopharyngeal cancer Fa Du cells and normal epithelial cells were detected by western blot.Lentivirus transfection technique was used to knock down the expression of RBM17 in Fa Du cells and construct Fa Du cell lines with stable low expression of RBM17.The relationship between RBM17 and cisplatin sensitivity was detected by CCK8 assay and q RT-PCR.Transwell test were used to detect the effect of RBM17 knockdown on Fa Du migration and invasion ability,and q RT-PCR and western blot were used to detect the effect of RBM17 on EMT process.The differentially expressed proteins in Fa Du cells after RBM17 knockdown were screened by Tandem Mass Tag(TMT)and LC-MS/MS,and verified by parallel reaction monitoring(PRM)and Western blot.Finally,we studied the effect of RBM17 on the growth of hypopharyngeal carcinoma in mice.Results: GEPIA and UALCAN data platforms showed that RBM17 was highly expressed in tumors(P<0.001),and the overall survival time and disease-free survival time of patients with high RBM17 expression were decreased(P<0.05).The expression level of RBM17 in hypopharyngeal carcinoma tissues and Fa Du cells was significantly increased(P<0.05).The expression of RBM17 was increased in Fa Du cells after cisplatin treatment(P<0.01),and RBM17 knockdown could enhance the sensitivity of Fa Du cells to cisplatin(P<0.01).Knockdown of RBM17 inhibited the migration and invasion of Fa Du cells in vitro(P<0.05),and reversed EMT,increased expression of Ecadherin(P<0.01),decreased expression of ZEB1 and Vimentin(P<0.01).LC-MS/MS and independent PRM analysis revealed 21 differentially expressed proteins associated with RBM17.Knockdown of RBM17 inhibits tumorigenic capacity of Fa Du cells in vivo(P<0.05).Conclusions: Our study suggests that knockdown of RBM17 may serve as a novel pathway to increase cisplatin sensitivity in HSCC and inhibit cell migration,invasion,and EMT.