Antisense oligonucleotide against miR-21 inhibits migration and induces apoptosis in leukemic K562 cells.
MicroRNAs (miRNAs) are small non-coding RNA molecules that are widely involved in cancer-related processes. The microRNA-21 (miR-21) has been identified as the only miRNA overexpressed in a variety of cancers, including leukemia. However, the function of miR-21 is yet unknown in chronic myelogenous leukemia (CML). Antisense oligonucleotides (ASOs), as inhibitors of miRNAs, have already been applied to therapeutic development and functional identification in miRNA research. In this study, we found that the antisense inhibition of miR-21 in K562 cells suppressed cell migration, promoted cell apoptosis, and inhibited cell growth, and up-regulated the expression of the tumor suppressor gene PDCD4. Meanwhile, pre-miRNA-21 increased migration and decreased cell apoptosis without affecting proliferation. We also validated that PDCD4 is a functional target of miR-21 in K562 cells. These effects of miR-21 might be partially due to its regulation of PDCD4. Our data suggest that miR-21 may play an oncogenic role in the cellular processes of CML, and antisense inhibition of miR-21 may therefore be useful as CML therapy.
Hu
Haiyan
H
Department of Biochemistry and Molecular Biology, Medical College of Jinan University, Guangzhou 510632, China.
Li
Yumin
Y
Gu
Jingyi
J
Zhu
Xujiao
X
Dong
Dawei
D
Yao
Junlin
J
Lin
Chunyan
C
Fei
Jia
J
D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects* / Q000235:genetics; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D004353:Drug Evaluation, Preclinical; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D020014:K562 Cells; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics / Q000473:pathology*; D035683:MicroRNAs / Q000037:antagonists & inhibitors* / Q000235:genetics; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D054928:Validation Studies as Topic
D051017:Apoptosis Regulatory Proteins; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D016376:Oligonucleotides, Antisense; C114487:PDCD4 protein, human; D016601:RNA-Binding Proteins