miR-221-3p Delivered by BMMSC-Derived Microvesicles Promotes the Development of Acute Myelocytic Leukemia

被引:12
作者
Zhang, Xuewu [1 ]
Xu, Yu [1 ]
Wang, Jinghan [1 ]
Zhao, Shuqi [1 ]
Li, Jianhu [1 ]
Huang, Xin [1 ]
Xu, Huan [1 ]
Zhang, Xiang [1 ]
Suo, Shanshan [1 ]
Lv, Yunfei [1 ]
Zhang, Yi [1 ]
Yu, Wenjuan [1 ]
机构
[1] Zhejiang Univ, Dept Hematol, Affiliated Hosp 1, Sch Med, Hangzhou, Peoples R China
来源
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY | 2020年 / 8卷
基金
中国国家自然科学基金;
关键词
BMMSC; microvesicles; miR-221-3p; AML; cell proliferation and invasion; cell cycle; INHIBITS CELL-PROLIFERATION; EXTRACELLULAR VESICLES; BONE-MARROW; CANCER; EXPRESSION; APOPTOSIS; EXOSOMES; CDKN1C;
D O I
10.3389/fbioe.2020.00081
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Objective: The study aims to investigate the effects of miR-221-3p in bone marrow mesenchymal stem cell (BMMSC)-derived microvesicles (MVs) on cell cycle, proliferation and invasion of acute myelocytic leukemia (AML). Methods: Bioinformatics was used to predict differentially expressed miRNAs (DEmiRNAs) in AML. The morphology of BMMSC-derived MVs was observed under an electron microscope, and the positional relation of MVs and OCI-AML2 cells was observed by a fluorescence microscope. MTT, Transwell, and flow cytometry assays were used to analyze the effects of MVs on OCI-AML2 cells. The targeted relationship between miR-221-3p and CDKN1C was detected by dual luciferase assay. Results: It was verified that miR-221-3p promoted the proliferation, invasion and migration of OCI-AML2 cells, and induced the cell cycle arrest in G1/S phase as well as inhibited cell apoptosis. Further studies showed that MVs promoted the proliferation, migration and invasion of AML, and induced the cell cycle arrest in G1/S phase through miR-221-3p. It was confirmed that miR-221-3p can directly target CDKN1C to regulate cell cycle, proliferation and invasion of AML. Conclusion: miR-221-3p in BMMSC-derived MVs regulated AML cell cycle, cell proliferation and invasion through targeting CDKN1C. miR-221-3p and CDKN1C were considered to be potential targets and biomarkers for the treatment of AML in clinic.
引用
收藏
页数:11
相关论文
共 39 条
  • [1] Vesicles bearing gifts: the functional importance of micro-RNA transfer in extracellular vesicles in chronic kidney disease
    Abbasian, Nima
    Herbert, Karl E.
    Pawluczyk, Izabella
    Burton, James O.
    Bevington, Alan
    [J]. AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY, 2018, 315 (05) : F1430 - F1443
  • [2] Intrinsic structural disorder and sequence features of the cell cycle inhibitor p57Kip2
    Adkins, JN
    Lumb, KJ
    [J]. PROTEINS-STRUCTURE FUNCTION AND GENETICS, 2002, 46 (01): : 1 - 7
  • [3] Exosomes in acute myeloid leukemia inhibit hematopoiesis
    Boyiadzis, Michael
    Whiteside, Theresa L.
    [J]. CURRENT OPINION IN HEMATOLOGY, 2018, 25 (04) : 279 - 284
  • [4] Exosomes as divine messengers: are they the Hermes of modern molecular oncology?
    Braicu, C.
    Tomuleasa, C.
    Monroig, P.
    Cucuianu, A.
    Berindan-Neagoe, I.
    Calin, G. A.
    [J]. CELL DEATH AND DIFFERENTIATION, 2015, 22 (01) : 34 - 45
  • [5] Molecular therapy for acute myeloid leukaemia
    Coombs, Catherine C.
    Tallman, Martin S.
    Levine, Ross L.
    [J]. NATURE REVIEWS CLINICAL ONCOLOGY, 2016, 13 (05) : 305 - 318
  • [6] Hematopoietic stem cell transplantation for patients with AML in first complete remission
    Cornelissen, Jan J.
    Blaise, Didier
    [J]. BLOOD, 2016, 127 (01) : 62 - 70
  • [7] Extracellular vesicles of bone marrow stromal cells rescue chronic lymphocytic leukemia B cells from apoptosis, enhance their migration and induce gene expression modifications
    Crompot, Emerence
    Van Damme, Michael
    Pieters, Karlien
    Vermeersch, Marjorie
    Perez-Morga, David
    Mineur, Philippe
    Maerevoet, Marie
    Meuleman, Nathalie
    Bron, Dominique
    Lagneaux, Laurence
    Stamatopoulos, Basile
    [J]. HAEMATOLOGICA, 2017, 102 (09) : 1594 - 1604
  • [8] Thrombosis in adult patients with acute leukemia
    Del Principe, Maria Ilaria
    Del Principe, Domenico
    Venditti, Adriano
    [J]. CURRENT OPINION IN ONCOLOGY, 2017, 29 (06) : 448 - 454
  • [9] The investigation of miR-221-3p and PAK1 gene expressions in breast cancer cell lines
    Ergun, Sercan
    Tayeb, Tayeb Sadiq
    Arslan, Ahmet
    Temiz, Ebru
    Arman, Kaifee
    Safdar, Muhammad
    Dagli, Hasan
    Korkmaz, Murat
    Nacarkahya, Gulper
    Kirkbes, Sevil
    Oztuzcu, Serdar
    [J]. GENE, 2015, 555 (02) : 377 - 381
  • [10] The emerging role of exosome-derived non-coding RNAs in cancer biology
    Fan, Qing
    Yang, Liang
    Zhang, Xiaodong
    Peng, Xueqiang
    Wei, Shibo
    Su, Dongming
    Zhai, Zhenhua
    Hua, Xiangdong
    Li, Hangyu
    [J]. CANCER LETTERS, 2018, 414 : 107 - 115