title: MicroRNA-374b Suppresses Proliferation and Promotes Apoptosis in T-cell Lymphoblastic Lymphoma by Repressing AKT1 and Wnt-16.
abstract: OBJECTIVE
  Deregulation of microRNA (miRNA) has been extensively investigated in both Hodgkin and non-Hodgkin lymphomas (NHL); however, little is known about the roles of miRNAs in T-cell lymphoblastic lymphoma (T-LBL). The aim of the present study was to investigate the potential roles of miR-374b in the development and treatment of T-LBL.
  
  
  METHODS
  MiRCURY LNA array was used to generate a miRNA-expressing profile. Real-time quantitative PCR and immunohistochemistry (IHC) were applied to detect the expression of miR-374b, AKT1, and Wnt16 in T-LBL samples. The dual-luciferase reporter assay was conducted to confirm target associations of miR-374b. The tumor-suppressive effect of miR-374b was determined by both in vitro and in vivo studies.
  
  
  RESULTS
  The expression of 380 miRNAs was evaluated in five human T-LBL tissues and five infantile thymus samples by microRNA microarrays. Downregulation of miR-374b was frequently detected in primary T-LBL tissues, which was significantly associated with worse overall survival and increased risk of recurrence of the 58 patients enrolled in this study. miR-374b suppressed T-LBL cell proliferation in vitro and in vivo and sensitized cells to serum starvation- and chemotherapeutic agent-induced apoptosis. Furthermore, we characterized two AKT pathway-associated molecules, AKT1 and Wnt16, as direct targets of miR-374b. Consistently, in T-LBL patient tissues, AKT1 and Wnt16 expression was inversely correlated with miR-374b levels, and was an independent predictor of recurrence and survival.
  
  
  CONCLUSIONS
  Our data highlight the molecular etiology and clinical significance of miR-374b in T-LBL. Targeting miR-374b may represent a new therapeutic strategy to improve therapy and survival for T-LBL patients.
authors.affiliation: Department of Radiotherapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, P.R. China. State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-Sen University, Collaborative Innovation Center of Cancer Medicine, Guangzhou, P.R. China.
authors.forename: Dong
authors.initials: D
authors.lastname: Qian
authors.affiliation: State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-Sen University, Collaborative Innovation Center of Cancer Medicine, Guangzhou, P.R. China. Department of Medical Oncology, Cancer Center, Sun Yat-sen University, Guangzhou, P.R. China.
authors.forename: Kailin
authors.initials: K
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-Sen University, Collaborative Innovation Center of Cancer Medicine, Guangzhou, P.R. China.
authors.forename: Haixia
authors.initials: H
authors.lastname: Deng
authors.affiliation: State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-Sen University, Collaborative Innovation Center of Cancer Medicine, Guangzhou, P.R. China. Department of Pathology, Cancer Center, Sun Yat-sen University, Guangzhou, P.R. China.
authors.forename: Huilan
authors.initials: H
authors.lastname: Rao
authors.affiliation: State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-Sen University, Collaborative Innovation Center of Cancer Medicine, Guangzhou, P.R. China. Department of Medical Oncology, Cancer Center, Sun Yat-sen University, Guangzhou, P.R. China.
authors.forename: Huiqiang
authors.initials: H
authors.lastname: Huang
authors.affiliation: State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-Sen University, Collaborative Innovation Center of Cancer Medicine, Guangzhou, P.R. China.
authors.forename: Yiji
authors.initials: Y
authors.lastname: Liao
authors.affiliation: State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-Sen University, Collaborative Innovation Center of Cancer Medicine, Guangzhou, P.R. China. Department of Pediatric Oncology, Cancer Center, Sun Yat-sen University, Guangzhou, P.R. China.
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Sun
authors.affiliation: State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-Sen University, Collaborative Innovation Center of Cancer Medicine, Guangzhou, P.R. China. Department of Pediatric Oncology, Cancer Center, Sun Yat-sen University, Guangzhou, P.R. China.
authors.forename: Suying
authors.initials: S
authors.lastname: Lu
authors.affiliation: Department of Radiotherapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, P.R. China.
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Yuan
authors.affiliation: State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-Sen University, Collaborative Innovation Center of Cancer Medicine, Guangzhou, P.R. China. Department of Pathology, Cancer Center, Sun Yat-sen University, Guangzhou, P.R. China. caiqq@sysucc.org.cn xied@mail.sysu.edu.cn.
authors.forename: Dan
authors.initials: D
authors.lastname: Xie
authors.affiliation: State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-Sen University, Collaborative Innovation Center of Cancer Medicine, Guangzhou, P.R. China. Department of Medical Oncology, Cancer Center, Sun Yat-sen University, Guangzhou, P.R. China. caiqq@sysucc.org.cn xied@mail.sysu.edu.cn.
authors.forename: Qingqing
authors.initials: Q
authors.lastname: Cai
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D001483:Base Sequence; D001665:Binding Sites; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D016000:Cluster Analysis; D004195:Disease Models, Animal; D015536:Down-Regulation; D020869:Gene Expression Profiling; D015973:Gene Expression Regulation, Leukemic; D064593:Heterografts; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000737:chemistry / Q000235:genetics*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D011379:Prognosis; D051057:Proto-Oncogene Proteins c-akt / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D034622:RNA Interference; D015398:Signal Transduction; D047368:Tumor Burden / Q000235:genetics; D051153:Wnt Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism
chemical_list: C587995:MIRN374 microRNA 374, human; D035683:MicroRNAs; C417262:WNT16 protein, human; D051153:Wnt Proteins; C494918:AKT1 protein, human; D051057:Proto-Oncogene Proteins c-akt