title: microRNA‑125b promotes leukemia cell resistance to daunorubicin by inhibiting apoptosis.
abstract: microRNA-125b (miR-125b) is overexpressed in several types of cancer and contributes to tumor resistance to chemotherapy. The present study investigated the effect of miR-125b on the resistance of leukemia cell lines to the chemotherapeutic agent daunorubicin (DNR). miR-125b expression was found to be upregulated in patients who had failed therapy compared with those who demonstrated event-free survival. The overexpression of miR-125b was observed to induce DNR resistance in K562, THP‑1 and Jurkat cells by reducing apoptosis, whereas the suppression of miR-125b was found to enhance DNR cytotoxicity in REH cells. Furthermore, miR-125b was observed to mediate DNR resistance in leukemia cell lines through decreasing expression of G protein-coupled receptor kinase 2 and p53-upregulated modulator of apoptosis, which were shown to be direct targets of miR-125b using a dual-luciferase reporter. The present study provides a novel mechanism for understanding leukemia drug resistance and provides a novel method for calculating patient prognosis.
authors.affiliation: Department of Hematology, Shanghai Jiaotong University, Affiliated Shanghai First People's Hospital, Shanghai 200080, P.R. China.
authors.forename: Lili
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Department of Hematology, Shanghai Jiaotong University, Affiliated Shanghai First People's Hospital, Shanghai 200080, P.R. China.
authors.forename: Haitao
authors.initials: H
authors.lastname: Bai
authors.affiliation: Department of Hematology, Shanghai Jiaotong University, Affiliated Shanghai First People's Hospital, Shanghai 200080, P.R. China.
authors.forename: Chun
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Hematology, Shanghai Jiaotong University, Affiliated Shanghai First People's Hospital, Shanghai 200080, P.R. China.
authors.forename: Daolin
authors.initials: D
authors.lastname: Wei
authors.affiliation: Department of Hematology, Shanghai Jiaotong University, Affiliated Shanghai First People's Hospital, Shanghai 200080, P.R. China.
authors.forename: Youwen
authors.initials: Y
authors.lastname: Qin
authors.affiliation: Department of Hematology, Shanghai Jiaotong University, Affiliated Shanghai First People's Hospital, Shanghai 200080, P.R. China.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Xu
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics; D045744:Cell Line, Tumor; D003630:Daunorubicin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D054769:G-Protein-Coupled Receptor Kinase 2 / Q000235:genetics; D015870:Gene Expression; D015973:Gene Expression Regulation, Leukemic; D055785:Gene Knockdown Techniques; D006801:Humans; D007938:Leukemia / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D011518:Proto-Oncogene Proteins / Q000235:genetics; D055815:Young Adult
chemical_list: D051017:Apoptosis Regulatory Proteins; C438378:BBC3 protein, human; C531888:MIRN125 microRNA, human; D035683:MicroRNAs; D011518:Proto-Oncogene Proteins; D054769:G-Protein-Coupled Receptor Kinase 2; D003630:Daunorubicin