miR-223通过Lmo2基因和MAPK信号通路调控急性淋巴细胞白血病的恶性生物学行为被引量：2

miR-223 regulates malignant biological behavior of acute lymphoblastic leukemia cells through targeting Lmo2 gene and MAPK signal pathway

原文传递

导出

摘要目的:探讨mi R-223调控急性淋巴细胞白血病(acute lymphoblastic leukemia,ALL)E6-1细胞的增殖和体内成瘤能力及其作用机制。方法:应用实时荧光定量PCR检测mi R-223在不同ALL细胞株中的表达水平,免疫荧光染色法检测携带mi R-223mimic慢病毒感染E6-1细胞株的感染效率,双荧光素酶实验检测mi R-223和Lmo2的相互结合关系,MTT增殖实验和克隆形成实验检测过表达mi R-223对E6-1细胞株增殖和克隆形成能力的影响。裸鼠体内成瘤实验检测mi R-223过表达对E6-1细胞成瘤能力的影响。Western blotting检测mi R-223对MAPK信号通路相关蛋白表达的影响。结果:mi R-223在E6-1细胞株中表达水平相对较低(P<0.05),双荧光素酶实验证实mi R-223可以直接靶向结合Lmo2的3’UTR区序列。过表达mi R-223后:(1)抑制E6-1细胞的增殖能力(0.16±0.02 vs 1.15±0.21,P<0.05);(2)抑制E6-1细胞的裸鼠体内成瘤能力[(0.56±0.08)vs(1.69±0.22)g,P<0.05];(3)调控MAPK信号通路的活性。结论:mi R-223可靶向作用Lmo2通过MAPK信号通路调控ALL细胞的增殖、克隆形成和体内成瘤能力。 Objective：To investigate the effect and mechanism of mi R-223 regulating the proliferation and in vivo tumorigenesis of acute lymphoblastic leukemia（ALL） E6-1 cells.Methods：The expression of mi R-223 in different ALL cell lines was detected by Real-time fluorescence quantitative PCR.Immunofluorescence was used to detect the transfection efficiency of mi R-223mimic-lenitvirus transfected E6-1 cell line.Double luciferase assay was used to detect the binding between mi R-223 and Lmo2.MTT assay and clone formation assay were used to detect the effect of mi R-223 on the proliferation and clone formation ability of E6-1 cell line.The effect of mi R-223 expression on the tumorigenic ability of E6-1 cells was detected by xenograft formation in nude mice.Western blotting was used to detect the effect of mi R-223 on the expressions of MAPK signal pathway related proteins.Results：The expression level of mi R-223 in E6-1 cell line was relatively low（P〈0.05）.Double luciferase assay confirmed that mi R-223 could directly target the 3＇UTR of Lmo2.Overexpression of mi R-223 inhibited the proliferation（0.16±0.02 vs1.15±0.21,P〈0.05） and tumorigenesis（[0.56±0.08]g vs [1.69±0.22]g,P〈0.05） of E6-1 cells and regulated the activity of MAPK signal pathway.Conclusion：mi R-223 can regulate the proliferation,clone formation and in vivo tumorigenesis of ALL cells through targeting Lmo2 and MAPK signal pathway.

作者陈丽赵红勉

机构地区河南大学淮河医院血液科

出处《中国肿瘤生物治疗杂志》 CAS CSCD 北大核心 2017年第9期944-949,共6页 Chinese Journal of Cancer Biotherapy

关键词 miRNA-133 Lmo2基因急性淋巴细胞白血病 E6-1细胞 MAPK信号通路 miR-223 Lmo2 gene acute lymphoblastic leukemia E6-1 cell line MAPK signal pathway

分类号 R733.71 [医药卫生—肿瘤] R730.2 [医药卫生—肿瘤]

引文网络
相关文献

参考文献1

1龙潺,唐雪元,郑方英,王春莲,胡俊.miRNA-19b在急性淋巴细胞白血病发病中的作用机制[J].中国老年学杂志,2016,36(19):4724-4726. 被引量：3

二级参考文献15

1Minervina AA, Komkov AY, Mamedov IZ, et al. Advanced lymphoblastic clones detection in T-cell leukemia[J]. Dokl Biochem Biophys,2016; 467( 1 ) :85-8.
2Yeh CH, Moles R, Nicot C. Clinical significance of microRNAs in chronic and acute human leukemia [J]. Mol Cancer, 2016 ; 15 ( 1 ) : 1-16.
3Dong X, Sui C, Huang K, et al. MicroRNA-223-3p suppresses leukemia inhibitory factor expression and pinopodes formation during embryo im- plantation in mice [J]. Am J Transl Res,2016 ;8 (2) : 1155-63.
4Li 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.
5de 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.
6Amin NA, Malek SN. Gene mutations in chronic lymphocytic leukemia [J].Semin Oncol,2016 ;43 (2) :215-21.
7Lu Y ,Wu D ,Wang J ,et al. miR-320a regulates cell proliferation and ap- optosis in multiple myeloma by targeting pre-B-cell leukemia transcription factor [J]. Bioehem Biophys Res Commun,2016 ;473 (4) :1315-20.
8Zhang W, Sun JZ, Han Y,et al. CXCL12/CXCR4 signaling pathway regu- lates cochlear development in neonatal mice [J]. Mol Med Rep ,2016 ;13 (5) :4357-64.
9Wang J J, Wang ZY, Chen R,et al. Macrophage-secreted exosomes delive- ring miRNA-21 inhibitor can regulate BGC-823 cell proliferation [J]. A- sian Pac J Cancer Prey,2015 ; 16(10) :4203-9.
10Wang J, Song S, Xie C, et al. MicroRNA profiling in the left atrium in patients with non-valvular paroxysmal atrial fibrillation [J].BMC Card- iovasc Disord,2015 ;15(5) :1-7.