title: MicroRNA181a Is Overexpressed in T-Cell Leukemia/Lymphoma and Related to Chemoresistance.
abstract: 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, miR181a could be a potential therapeutic target in treating T-cell malignancies.
authors.affiliation: State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Shanghai Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, China ; French-Chinese Laboratory of Genomic and Life Sciences, Laboratory of Molecular Pathology, Shanghai 200025, China.
authors.forename: Zi-Xun
authors.initials: ZX
authors.lastname: Yan
authors.affiliation: State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Shanghai Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, China ; French-Chinese Laboratory of Genomic and Life Sciences, Laboratory of Molecular Pathology, Shanghai 200025, China.
authors.forename: Zhong
authors.initials: Z
authors.lastname: Zheng
authors.affiliation: State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Shanghai Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, China ; French-Chinese Laboratory of Genomic and Life Sciences, Laboratory of Molecular Pathology, Shanghai 200025, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Xue
authors.affiliation: Department of Hematology, Central Hospital of Jinhua, Zhejiang 321000, China.
authors.forename: Ming-Zhe
authors.initials: MZ
authors.lastname: Zhao
authors.affiliation: Department of Pathology, Shanghai Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, China.
authors.forename: Xiao-Chun
authors.initials: XC
authors.lastname: Fei
authors.affiliation: Department of Pathology, Shanghai Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, China.
authors.forename: Li-Li
authors.initials: LL
authors.lastname: Wu
authors.affiliation: Department of Oncology, People's Hospital of Guizhou Province, Guiyang 550001, China.
authors.forename: Li-Min
authors.initials: LM
authors.lastname: Huang
authors.affiliation: Laboratory of Pathology, Paris Diderot University, U1165 Inserm, 75010 Paris, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Leboeuf
authors.affiliation: Laboratory of Pathology, Paris Diderot University, U1165 Inserm, 75010 Paris, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Janin
authors.affiliation: State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Shanghai Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, China ; French-Chinese Laboratory of Genomic and Life Sciences, Laboratory of Molecular Pathology, Shanghai 200025, China.
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Shanghai Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, China ; French-Chinese Laboratory of Genomic and Life Sciences, Laboratory of Molecular Pathology, Shanghai 200025, China.
authors.forename: Wei-Li
authors.initials: WL
authors.lastname: Zhao
mesh_terms: D000328:Adult; D000970:Antineoplastic Agents / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000235:genetics; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects; D057809:HEK293 Cells; D006801:Humans; D019169:Jurkat Cells; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D054218:Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / Q000201:enzymology / Q000235:genetics*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; C540193:MIrn181 microRNA, human; D035683:MicroRNAs; D004317:Doxorubicin; D051057:Proto-Oncogene Proteins c-akt