Liu Jing, Lin Jin, Huang Lin-Feng, Huang Bo, Xu Yan-Mei, Li Jing, Wang Yan, Zhang Jing, Yang Wei-Ming, Min Qing-Hua, Wang Xiao-Zhong
Department of Clinical Laboratory, The Second Affiliated Hospital of Nanchang University, No. 1 Min De Road, Nanchang, 330006, China.
Department of Clinical Laboratory, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, China.
Tumour Biol. 2015 Sep;36(10):8127-36. doi: 10.1007/s13277-015-3493-0. Epub 2015 May 17.
Cancer progression often involves the disorder of the cell cycle, and a number of effective chemotherapeutic drugs have been shown to induce cell cycle arrest. The purpose of this study was to comprehensively investigate the effects of imatinib on the expression profile of cell cycle genes in the chronic myeloid leukemia (CML) K562 cell line. In addition, we also investigated alternative splicing of the cell cycle genes affected by imatinib, since an important relationship has been shown to exist between RNA splicing and cell cycle progression. Exon array analysis was performed using total RNA purified from normal and imatinib-treated K562 cells. We identified 185 differentially expressed genes and 277 alternative splicing events between the two cell groups. A detailed analysis by reverse transcription-PCR (RT-PCR) of key genes confirmed the experimental results of the exon array. These results suggested that treatment of K562 cells with imatinib shifts the expression and alternative splicing profiles of several cell cycle-related genes. Importantly, these findings may help improve imatinib treatment strategies in patients with CML and may be useful for imatinib resistance research and CML drug development.
癌症进展通常涉及细胞周期紊乱，并且已证明多种有效的化疗药物可诱导细胞周期停滞。本研究的目的是全面研究伊马替尼对慢性髓性白血病（CML）K562细胞系中细胞周期基因表达谱的影响。此外，我们还研究了受伊马替尼影响的细胞周期基因的可变剪接，因为已证明RNA剪接与细胞周期进程之间存在重要关系。使用从正常和伊马替尼处理的K562细胞中纯化的总RNA进行外显子阵列分析。我们在两个细胞组之间鉴定出185个差异表达基因和277个可变剪接事件。通过逆转录PCR（RT-PCR）对关键基因进行的详细分析证实了外显子阵列的实验结果。这些结果表明，用伊马替尼处理K562细胞会改变几个细胞周期相关基因的表达和可变剪接谱。重要的是，这些发现可能有助于改善CML患者的伊马替尼治疗策略，并且可能对伊马替尼耐药性研究和CML药物开发有用。
