Ribosomal protein L23 negatively regulates cellular apoptosis via the RPL23/Miz-1/c-Myc circuit in higher-risk myelodysplastic syndrome

• DOI: 10.1038/s41598-017-02403-x
• Publication Date: 2017-05-18T09:55:26Z
• Authors: Yuekun Qi; Xiao Li; Chunkang Chang; Feng Xu; Qi He; Youshan Zhao; Lingyun Wu
• Keywords: Adult; Cyclin-Dependent Kinase Inhibitor p21; Male; Ribosomal Proteins; Transcriptional Activation; 0301 basic medicine; Adolescent; Science; Kruppel-Like Transcription Factors; Apoptosis; Article; Proto-Oncogene Proteins c-myc; 03 medical and health sciences; Humans; Promoter Regions, Genetic; Aged; Aged, 80 and over; 0303 health sciences; Q; R; Cell Cycle Checkpoints; Middle Aged; Microarray Analysis; Gene Expression Regulation; Myelodysplastic Syndromes; Medicine; Female; Signal Transduction

Ribosomal protein (RP) L23 is a negative regulator of cellular apoptosis, and RPL23 overexpression associated with abnormal apoptotic resistance in CD34+ cells derived from patients higher-risk myelodysplastic syndrome (MDS). However, the mechanism underlying RPL23-induced MDS poorly understood. In this study, we showed that reduced expression led to suppressed viability, increased apoptosis G1-S cell cycle arrest. Gene microarray analysis comparing RPL23-knockdown control identified an array differentially expressed genes, which, Miz-1, was upregulated transactivation inhibitors p15Ink4b p21Cip1, Miz-1's functional repressor, c-Myc, downregulated. Cells demonstrated consistently c-Myc decreased Miz-1 compared lower-risk patients. conclusion, Miz-1-dependent induction p21Cip1 depressed under conditions elevated expression, leading Because encoded by target gene RPL23/Miz-1/c-Myc regulatory circuit provides feedback loop links efficient c-Myc's function suppress Miz-1-induced Cdk thereby leads