miRNA-regulated expression of oncogenes and tumor suppressor genes in the cisplatin-inhibited growth of K562 cells
miRNA-regulated expression of oncogenes and tumor suppressor genes in the cisplatin-inhibited growth of K562 cells
复制标题
顺铂抑制K562细胞生长中癌基因和抑癌基因的miRNA调控表达
DOI：
10.3892/or_00000813
复制
发表时间：
2010-06-01
期刊：
影响因子：
4.2
通讯作者：
Zhang, Wen-Juan
中科院分区：
文献类型：
--
作者：
Xie, Shu-Yang;Li, You-Jie;Zhang, Wen-Juan
为探讨顺铂诱导K562细胞凋亡的机制，采用逆转录聚合酶链式反应、实时荧光定量聚合酶链式反应和酶联免疫吸附试验检测了K562细胞中microRNAs(MiRNAs)及其调控基因的表达。结果显示，经顺铂治疗后，miR-16、miR-34a-c、miR-17-5p和miR-125表达上调，其相关癌基因(分别为bcl2、E2F1和E2F3)表达上调。顺铂治疗后，miR-106和miR-150基因表达下调，而靶基因(分别为RB1和P53)表达上调。此外，miR-16、miR-34a-c和miR-17-5p分别是调控bcl2、E2F1和E2F3表达的上游因子。反义寡核苷酸(ASO)处理后，RB1基因表达上调，癌基因E2F3表达下调。类似地，当ASO处理上调P53表达时，BCL2和E2F3表达下调。研究表明，顺铂通过下调上调RB1的miR-106或抑制上调P53表达的miR-150诱导K562细胞凋亡。
To explore the mechanism of apoptosis induced by cisplatin, the expression of microRNAs (miRNAs) and regulating genes in K562 cells was analyzed using reverse transcription PCR, quantitative real-time PCR and enzyme-linked immunosorbent assays. Our results showed that miR-16, miR-34a-c, miR-17-5p and miR-125 were up-regulated, and their associated oncogenes (BCL2, E2F1 and E2F3, respectively) were clown-regulated after cisplatin treatment. We also showed that miR-106 and miR-150 were down-regulated while their target genes (RB1 and P53, respectively) were up-regulated after cisplatin treatment. Moreover, miR-16, miR-34a-c and miR-17-5p proved to be upstream factors, regulating the expression of BCL2, E2F1 and E2F3, respectively. The oncogene E2F3 was down-regulated when RB1 expression was increased after treatment with antisense oligonucleotides (ASO). Similarly, BCL2 and E2F3 were down-regulated when P53 expression was elevated by ASO treatment. The study demonstrated that cisplatin induces K562 cells to apoptosis by reducing miR-106 which up-regulates RB1 or by inhibiting miR-150 which increases P53 expression.