MicroRNA181a is overexpressed in T-cell leukemia/lymphoma and related to chemoresistance
MicroRNAs (miRs) play an important role in tumorogenesis and chemoresistance in lymphoid malignancies.Comparing with reactive hyperplasia, miR181a was overexpressed in 130 patients with T-cell leukemia/lymphoma, including acute T-cell lymphoblastic leukemia (n=32), T-cell lymphoblastic lymphoma (n=16), peripheral T-cell lymphoma, not otherwise specified (n=45), anaplastic large cell lymphoma (n=15) and angioimmunoblastic T-cell lymphoma (n=22).Irrespective to histological subtypes, miR181a overexpression was associated with increased AKT phosphorylation.In vitro, ectopic expression of miR181a in HEK-293T cells significantly enhanced cell proliferation, activated AKT and conferred cell resistance to doxorubicin.Meanwhile,miR181a expression was upregulated in Jurkat cells, along with AKT activation, during exposure to chemotherapeutic agents regularly applied to T-cell leukemia/lymphoma treatment, such as doxorubicin,cyclophosphamide, cytarabine and cisplatin.Isogenic doxorubicin-resistant Jurkat and H9 cells were subsequently developed, which also presented with miR181a overexpression and cross-resistance to cyclophosphamide and cisplatin.Meanwhile, specific inhibition of miR181a enhanced Jurkat and H9 cell sensitivity to chemotherapeutic agents, further indicating that miR181a was involved in acquired chemoresistance.Collectively, miR181a functioned as a biomarker of T-cell leukemia/lymphoma through modulation of AKT pathway.Related to tumor cell chemoresistance, miR181 a could be a potential therapeutic target in treating T-cell malignancies.
miR181a T-leukemia/lymphoma chemoresistance
Zi-Xun YAN Zhong ZHENG Wen XUE Xiao-Chun FEI Li-Li WU Li WANG Wei-Li ZHAO
Department of Hematology, Shanghai Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
国内会议
中国老年学学会老年肿瘤专业委员会2015年淋巴血液肿瘤分会年会
北京
英文
23-34
2015-04-10（万方平台首次上网日期，不代表论文的发表时间）