title: miR-203 inhibits proliferation and self-renewal of leukemia stem cells by targeting survivin and Bmi-1.
abstract: Drug resistance is one of the leading causes of failed cancer therapy in the treatment of acute myeloid leukemia. Although the mechanisms of resistance are poorly understood, they may be related to the presence of leukemia stem cells (LSCs). Down-regulation of the miR-203 reportedly contributes to oncogenesis and chemo-resistance in multiple cancers. We found that miR-203 expression was down-regulated in CD34 + AML cells as compared with CD34- cells isolated from patients as well as in LSC-enriched (CD34 + CD38-) cell lines KG-1a or MOLM13. Additionally, re-expression of miR-203 led to decreased cell proliferation, self-renewal, and sphere formation in LSCs. Moreover, miR-203 was found to directly target the 3'un-translated regions of survivin and Bmi-1 mRNAs affecting proliferation and self-renewal in LSCs. In this study, we identified a novel miR-203/survivin/Bmi-1 axis involved in the regulation of biological properties of LSCs. This axis may represent a new therapeutic target for acute myeloid leukemia and a potential prognosis/diagnostic marker for LSCs therapy.
authors: College of life science and technology, Jinan University, Guangzhou, 510632, P.R. China.|Institute of Biomedicine, Jinan University, Guangzhou, 510632, P.R. China.|Section of Otolaryngology, Department of Surgery, Yale School of Medicine, U.S.A.
authors: Yi
authors: Y
authors: Zhang
authors: Department of Pathological Physiology, Wan-nan Medical College, Wuhu, 241000, P.R. China.
authors: Shu-yan
authors: SY
authors: Zhou
authors: College of life science and technology, Jinan University, Guangzhou, 510632, P.R. China.
authors: Hai-zhao
authors: HZ
authors: Yan
authors: College of life science and technology, Jinan University, Guangzhou, 510632, P.R. China.
authors: Dan-dan
authors: DD
authors: Xu
authors: College of medicine, Jinan University, Guangzhou, 510632, P.R. China.
authors: Hai-xuan
authors: HX
authors: Chen
authors: Institute of Biomedicine, Jinan University, Guangzhou, 510632, P.R. China.
authors: Xiao-yan
authors: XY
authors: Wang
authors: Institute of Biomedicine, Jinan University, Guangzhou, 510632, P.R. China.
authors: Xiao
authors: X
authors: Wang
authors: College of life science and technology, Jinan University, Guangzhou, 510632, P.R. China.
authors: Yu-ting
authors: YT
authors: Liu
authors: College of life science and technology, Jinan University, Guangzhou, 510632, P.R. China.
authors: Li
authors: L
authors: Zhang
authors: College of life science and technology, Jinan University, Guangzhou, 510632, P.R. China.
authors: Sheng
authors: S
authors: Wang
authors: Department of Pathogen Biology and Immunology, Medical College, Guangdong Pharmaceutical University, Guangzhou 510006, China.
authors: Peng-jun
authors: PJ
authors: Zhou
authors: Department of Pathogen Biology and Immunology, Medical College, Guangdong Pharmaceutical University, Guangzhou 510006, China.
authors: Wu-yu
authors: WY
authors: Fu
authors: Department of Pathogen Biology and Immunology, Medical College, Guangdong Pharmaceutical University, Guangzhou 510006, China.
authors: Bi-bo
authors: BB
authors: Ruan
authors: College of life science and technology, Jinan University, Guangzhou, 510632, P.R. China.
authors: Dong-lei
authors: DL
authors: Ma
authors: College of life science and technology, Jinan University, Guangzhou, 510632, P.R. China.
authors: Ying
authors: Y
authors: Wang
authors: Institute of Biomedicine, Jinan University, Guangzhou, 510632, P.R. China.
authors: Qiu-ying
authors: QY
authors: Liu
authors: Institute of Biomedicine, Jinan University, Guangzhou, 510632, P.R. China.
authors: Zhe
authors: Z
authors: Ren
authors: Institute of Biomedicine, Jinan University, Guangzhou, 510632, P.R. China.
authors: Zhong
authors: Z
authors: Liu
authors: Department of Endoscopy, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China,Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510632, P.R. China.
authors: Rong
authors: R
authors: Zhang
authors: College of life science and technology, Jinan University, Guangzhou, 510632, P.R. China.|Institute of Biomedicine, Jinan University, Guangzhou, 510632, P.R. China.
authors: Yi-fei
authors: YF
authors: Wang
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D001483:Base Sequence; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015536:Down-Regulation; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015470:Leukemia, Myeloid, Acute / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism* / Q000627:therapeutic use; D014411:Neoplastic Stem Cells / Q000166:cytology / Q000378:metabolism*; D063150:Polycomb Repressive Complex 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D016415:Sequence Alignment; D000077022:Survivin
chemical_list: D020413:3' Untranslated Regions; D018952:Antigens, CD34; C107489:BIRC5 protein, human; C069077:BMI1 protein, human; D051034:Inhibitor of Apoptosis Proteins; C546703:MIRN203 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D000077022:Survivin; D063150:Polycomb Repressive Complex 1