| Purpose:To investigate the mechanism of ribosomal protein（RP）L23-mediated apoptotic regulation through c-Myc/Miz-1 pathway in myelodysplastic syndromes（MDS）and to elucidate the role of RPL23 overexpression in apoptotic resisitance happened in higher-risk MDS,as well as its potential influence on prognosis.Methods:RNA interferon was used to reduced RPL23 expression in SKM-1/K562cells and cell proliferation,cell apoptosis,cell cycle distribution and senescence signal of both cell lines were analyzed.Differentially expressed genes（DEGs）were obtained by gene expression profile chip,and significantly enriched gene sets were validated by qRT-PCR and western blot.RPL23 and c-Myc/Miz-1 expression was detected in MDS patients using methods of qRT-PCR and immunohistochemistry of bone marrow biopsy.The progression-free survival（PFS）and overall survival（OS）were analyzed.Results:（1）Suppressed cellular viability,increased apoptosis and G1-S cell cycle arrest were observed after RPL23-knockdown in SKM-1/K562 cells;gene microarray analysis of RPL23-knockdown SKM-1 cells identified an array of DEGs,of which,Miz-1,was upregulated with transactivation of the cell cycle inhibitors p15Ink4b and p21Cip1,and Miz-1’s functional repressor,c-Myc,was downregulated;induction of c-Myc expression in RPL23-knockdown SKM-1 cells rescued superinfected cells from proliferative inhibition and demonstrated reduced apoptosis.（2）RPL23expression was higher in higher-risk MDS than that in lower-risk and normal ones,and similar inclination was displayed in c-Myc level,but Miz-1 expressed higher in lower-risk patients;PFS and OS of RPL23-overexpressed MDS patients were reduced compared with its counterparts.Conclusions:The over-expression of RPL23 in higher-risk MDS may serve as a negative regulator of apoptosis through c-Myc/Miz-1 pathway.RPL23 over expression was more common detected in higher-risk MDS and correlated with poor prognosis. |
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