miRNA-19b在急性淋巴细胞白血病发病中的作用机制
摘要
目的探讨miRNA-19b对Notch1信号通路的调控作用及miRNA-19b调控下的Notch1信号通路在急性淋巴细胞白血病发病中的作用及机制。方法 Real-time PCR法检测急性淋巴细胞白血病中miRNA-19b和Notch1信号通路相关分子的表达水平。分别利用miRNA-19b前体片段及miRNA-19b anti-sense片段过表达及干扰miRNA-19b的表达,MTT法检测miRNA-19b过表达及干扰对急性淋巴细胞白血病患者单个核细胞数量的变化,同时利用Western印迹法检测miRNA-19b过表达及干扰后Notch1信号通路的激活水平。结果 (1)急性淋巴细胞白血病中miRNA-19b和Notch1信号通路相关分子Notch1及Hes5的表达水平较正常对照组显著升高(P<0.05)。(2)miRNA-19b过表达及干扰后MTT结果显示miRNA-19b可上调急性淋巴细胞白血病中单个核细胞的数量。(3)Western印迹检测显示miRNA-19b过表达可促进Notch1信号通路中Notch1及Hes5的表达,而miRNA-19b干扰后两分子的表达水平下调。结论 miRNA-19b通过激活Notch1信号通路促进急性淋巴细胞白血病的发病。
引文
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2 Yeh CH,Moles R,Nicot C.Clinical significance of microRNAs in chronic and acute human leukemia[J].Mol Cancer,2016;15(1):1-16.
3 Dong X,Sui C,Huang K,et al.MicroRNA-223-3p suppresses leukemia inhibitory factor expression and pinopodes formation during embryo implantation in mice[J].Am J Transl Res,2016;8(2):1155-63.
4 Li Q,Wu Y,Zhang J,et al.MicroRNA-130a regulates cell malignancy by targeting RECK in chronic myeloid leukemia[J].Am J Transl Res,2016;8(2):955-67.
5 de Carvalho IN,de Freitas RM,Vargas FR.Translating microRNAs into biomarkers:what is new for pediatric cancer[J]?Med Oncol,2016;33(5):1-12.
6 Amin NA,Malek SN.Gene mutations in chronic lymphocytic leukemia[J].Semin Oncol,2016;43(2):215-21.
7 Lu Y,Wu D,Wang J,et al.miR-320a regulates cell proliferation and apoptosis in multiple myeloma by targeting pre-B-cell leukemia transcription factor 3[J].Biochem Biophys Res Commun,2016;473(4):1315-20.
8 Wang JJ,Wang ZY,Chen R,et al.Macrophage-secreted exosomes delivering miRNA-21 inhibitor can regulate BGC-823 cell proliferation[J].A-sian Pac J Cancer Prev,2015;16(10):4203-9.
9 Zhang W,Sun JZ,Han Y,et al.CXCL12/CXCR4 signaling pathway regulates cochlear development in neonatal mice[J].Mol Med Rep,2016;13(5):4357-64.
10 Wang J,Song S,Xie C,et al.MicroRNA profiling in the left atrium in patients with non-valvular paroxysmal atrial fibrillation[J].BMC Cardiovasc Disord,2015;15(5):1-7.
11 Wang XC,Du LQ,Tian LL,et al.Expression and function of miRNA in postoperative radiotherapy sensitive and resistant patients of non-smal cell lung cancer[J].Lung Cancer,2011;72(1):92-9.
12 Patz M,Pallasch CP,Wendtner CM.Critical role of microRNAs in chronic lymphocytic leukemia:overexpression of the oncogene PLAG1 by deregulated miRNAs[J].Leuk Lymphoma,2010;51(8):1379-81.
13 Landskroner-Eiger S,Qiu C,Perrotta P,et al.Endothelial miR-17 approximately 92 cluster negatively regulates arteriogenesis via miRNA-19repression of WNT signaling[J].Proc Natl Acad Sci USA,2015;112(41):12812-7.
14 Carofino BL,Ayanga B,Tracey LJ,et al.PRDM14 promotes RAG-dependent Notch1 driver mutations in mouse T-ALL[J].Biol Open,2016;5(5):645-53.
15 Rasi S,Khiabanian H,Ciardullo C,et al.Clinical impact of small subclones harboring NOTCH1,SF3B1 or BIRC3 mutations in chronic lymphocytic leukemia[J].Haematologica,2016;52(1):330-9.