State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China.
State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China.
Biochem Biophys Res Commun. 2014 Apr 18;446(4):1204-10. doi: 10.1016/j.bbrc.2014.03.086. Epub 2014 Mar 26.
Ribosomal protein S27a (RPS27a) could perform extra-ribosomal functions besides imparting a role in ribosome biogenesis and post-translational modifications of proteins. The high expression level of RPS27a was reported in solid tumors, and we found that the expression level of RPS27a was up-regulated in advanced-phase chronic myeloid leukemia (CML) and acute leukemia (AL) patients. In this study, we explored the function of RPS27a in leukemia cells by using CML cell line K562 cells and its imatinib resistant cell line K562/G01 cells. It was observed that the expression level of RPS27a was high in K562 cells and even higher in K562/G01 cells. Further analysis revealed that RPS27a knockdown by shRNA in both K562 and K562G01 cells inhibited the cell viability, induced cell cycle arrest at S and G2/M phases and increased cell apoptosis induced by imatinib. Combination of shRNA with imatinib treatment could lead to more cleaved PARP and cleaved caspase-3 expression in RPS27a knockdown cells. Further, it was found that phospho-ERK(p-ERK) and BCL-2 were down-regulated and P21 up-regulated in RPS27a knockdown cells. In conclusion, RPS27a promotes proliferation, regulates cell cycle progression and inhibits apoptosis of leukemia cells. It appears that drugs targeting RPS27a combining with tyrosine kinase inhibitor (TKI) might represent a novel therapy strategy in TKI resistant CML patients.
核糖体蛋白 S27a(RPS27a)除了在核糖体生物发生和蛋白质翻译后修饰中发挥作用外,还具有额外的核糖体功能。已有研究报道,RPS27a 在实体瘤中高表达,我们发现 RPS27a 在慢性髓系白血病(CML)和急性白血病(AL)的晚期患者中的表达水平上调。在这项研究中,我们通过 CML 细胞系 K562 细胞及其伊马替尼耐药细胞系 K562/G01 细胞探索了 RPS27a 在白血病细胞中的功能。结果观察到,K562 细胞中 RPS27a 的表达水平较高,而 K562/G01 细胞中 RPS27a 的表达水平甚至更高。进一步分析表明,shRNA 下调 K562 和 K562G01 细胞中的 RPS27a 抑制细胞活力,诱导细胞周期停滞在 S 和 G2/M 期,并增加伊马替尼诱导的细胞凋亡。shRNA 与伊马替尼联合治疗可导致 RPS27a 下调细胞中更多的 PARP 和 caspase-3 裂解。此外,还发现 RPS27a 下调细胞中磷酸化 ERK(p-ERK)和 BCL-2 下调,P21 上调。总之,RPS27a 促进白血病细胞增殖,调节细胞周期进程,抑制细胞凋亡。似乎针对 RPS27a 的药物与酪氨酸激酶抑制剂(TKI)联合使用可能代表 TKI 耐药 CML 患者的一种新的治疗策略。