Anti-miR-21 oligonucleotide sensitizes leukemic K562 cells to arsenic trioxide by inducing apoptosis

作者：Li, Yumin; Zhu, Xuejiao; Gu, Jingyi; Dong, Dawei; Yao, Junlin; Lin, Chunyan; Huang, Kangkang; Fei, Jia^*

来源：CANCER SCIENCE, 2010, 101(4): 948-954.

DOI：10.1111/j.1349-7006.2010.01489.x

• ACUTE PROMYELOCYTIC LEUKEMIA
• TUMOR-SUPPRESSOR PDCD4
• MICRORNA TARGETS
• MESSENGER-RNAS
• CANCER-CELLS
• MIRNA
• INHIBITION
• EXPRESSION
• EFFICACY
• MIR-21

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. (Cancer Sci 2010; 101: 948-954)

• 出版日期2010-4
• 单位暨南大学