miRNA-regulated expression of oncogenes and tumor suppressor genes in the cisplatin-inhibited growth of K562 cells.
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 down-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.
Xie
Shu-Yang
SY
Institute of Medical Molecular Genetics, Department of Biochemistry and Molecular Biology, Bin Zhou Medical University, Shandong 264003, PR China. shuyangxie@yahoo.com.cn
Li
You-Jie
YJ
Wang
Ping-Yu
PY
Jiao
Fei
F
Zhang
Shuai
S
Zhang
Wen-Juan
WJ
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects*; D002945:Cisplatin / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D016147:Genes, Tumor Suppressor / Q000502:physiology*; D006801:Humans; D020014:K562 Cells; D035683:MicroRNAs / Q000502:physiology*; D009857:Oncogenes / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000970:Antineoplastic Agents; D035683:MicroRNAs; D012333:RNA, Messenger; D002945:Cisplatin