Anti-miR-21 oligonucleotide enhances chemosensitivity of leukemic HL60 cells to arabinosylcytosine by inducing apoptosis.
Drug insensitivity or resistance is a major obstacle for successful treatment of acute myeloid leukemia. MicroRNAs (miRNAs) are small non-coding RNA molecules. Increasing evidence suggests that miRNAs modulate cellular sensitivity to anticancer drugs. We used a specific anti-miR-21 oligonucleotide (AMO-miR-21) to sensitize leukemic HL60 cells to arabinosylcytosine (Ara-C) by down-regulating miR-21. AMO-miR-21 alone effectively inhibited HL60 cell viability as measured by MTT assays and induced apoptosis as evaluated by flow cytometry, whereas AMO-miR-21 in combination with Ara-C enhanced HL60 cells to Ara-C-sensitivity and promoted Ara-C-induced apoptosis. Levels of miR-21 and its target PDCD4, quantified by real-time PCR, showed that expression of miR-21 was significantly decreased after AMO-miR-21 treatment. PDCD4 as a direct target of miR-21 in leukemic HL60 cells was confirmed by the dual-luciferase reporter assay. Our study suggests that AMO-miR-21 significantly sensitizes HL60 cells to Ara-C by inducing apoptosis and these effects of AMO-miR-21 may be partially due to its up-regulation of PDCD4. Therefore, exploiting synergistic effects between AMO-miR-21 and Ara-C might be an effective clinical strategy for leukemia chemotherapy.
Li
Yumin
Y
Department of Biochemistry and Molecular Biology, Medical College of Jinan University, Guangzhou, China.
Zhu
Xuejiao
X
Gu
Jingyi
J
Hu
Haiyan
H
Dong
Dawei
D
Yao
Junlin
J
Lin
Chunyan
C
Fei
Jia
J
D020413:3' Untranslated Regions / Q000187:drug effects; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D003561:Cytarabine / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D004357:Drug Synergism; D017930:Genes, Reporter; D018922:HL-60 Cells; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy* / Q000378:metabolism; D035683:MicroRNAs / Q000037:antagonists & inhibitors* / Q000378:metabolism; D020319:Oligodeoxyribonucleotides, Antisense / Q000235:genetics / Q000494:pharmacology*; D009994:Osmolar Concentration; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D015854:Up-Regulation / Q000187:drug effects
D020413:3' Untranslated Regions; D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D020319:Oligodeoxyribonucleotides, Antisense; C114487:PDCD4 protein, human; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D003561:Cytarabine