Anti-miR-21 oligonucleotide sensitizes leukemic K562 cells to arsenic trioxide by inducing apoptosis.
Arsenic trioxide (ATO), an ancient traditional Chinese medicine, has been successfully used as a therapeutic agent for leukemia. Drug resistance and toxicity are major concerns with the treatment. MicroRNAs (miRNAs) are endogenous small non-coding RNA molecules that might modulate cellular sensitivity to anticancer drugs. miRNA-21 (miR-21) is one of the most prominent miRNAs involved in various aspects of human cancers. However, miR-21 has been rarely characterized in chronic myelogenous leukemia (CML). Here, we used a specific anti-miR-21 oligonucleotide (AMO-miR-21) to sensitize K562 cells to ATO by degradation of miR-21. The results showed that both AMO-miR-21 and ATO caused growth inhibition, apoptosis, and G1-phase arrest in K562 cells. Meanwhile, AMO-miR-21 significantly promoted ATO-mediated growth inhibition and apotosis without affecting the G1 phase. Apoptotic cells were confirmed morphologically with Giemsa's staining. Furthermore, dual-luciferase reporter vector, containing two tandem miR-21 binding sites from PDCD4 3'UTR, validated that PDCD4 was directly regulated by miR-21. Therefore, AMO-miR-21 sensitized leukemic K562 cells to ATO by inducing apoptosis partially due to its up-regulation of PDCD4 protein level. The combination of ATO and AMO-miR-21 present therapeutic potential for CML.
Department of Biochemistry, Medical College of Jinan University, Guangzhou, China.
Yumin
Y
Li
Xuejiao
X
Zhu
Jingyi
J
Gu
Dawei
D
Dong
Junlin
J
Yao
Chunyan
C
Lin
Kangkang
K
Huang
Jia
J
Fei
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000627:therapeutic use*; D002453:Cell Cycle / Q000235:genetics; D016193:G1 Phase / Q000235:genetics; D006801:Humans; D020014:K562 Cells; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics / Q000628:therapy*; D035683:MicroRNAs / Q000494:pharmacology*; D009841:Oligonucleotides / Q000494:pharmacology*; D010087:Oxides / Q000627:therapeutic use*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; D001152:Arsenicals; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D009841:Oligonucleotides; D010087:Oxides; C114487:PDCD4 protein, human; D016601:RNA-Binding Proteins; D000077237:Arsenic Trioxide