[1]冶鹏娟),程 振),崔建坡),等.过表达miR-100对急性淋巴细胞白血病细胞增殖、侵袭、迁移及CXCR7/STAT3轴蛋白表达的影响[J].郑州大学学报(医学版),2020,(06):852-857.[doi:10.13705/j.issn.1671-6825.2019.12.112]
　YE Pengjuan),CHENG Zhen),CUI Jianpo),et al.Overexpression of miR-100 inhibits proliferation,invasion and migration of acute lymphoblastic leukemia cells by targeting CXCR7/STAT3 axis[J].JOURNAL OF ZHENGZHOU UNIVERSITY(MEDICAL SCIENCES),2020,(06):852-857.[doi:10.13705/j.issn.1671-6825.2019.12.112]
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过表达miR-100对急性淋巴细胞白血病细胞增殖、侵袭、迁移及CXCR7/STAT3轴蛋白表达的影响()
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《郑州大学学报(医学版)》[ISSN:1671-6825/CN:41-1340/R]

卷:
期数:
2020年06期
页码:
852-857
栏目:
应用研究
出版日期:
2020-11-20

文章信息/Info

Title:
Overexpression of miR-100 inhibits proliferation,invasion and migration of acute lymphoblastic leukemia cells by targeting CXCR7/STAT3 axis
作者:
冶鹏娟1); 程 振2); 崔建坡1); 张文林3); 罗继霞1); 武水如1)
1)开封市儿童医院血液科 河南开封 475000 2)开封市中心医院病理科 河南开封 475000 3)郑州大学附属肿瘤医院血液科 郑州 450003
Author(s):
YE Pengjuan1); CHENG Zhen2); CUI Jianpo1); ZHANG Wenlin3); LUO Jixia1); WU Shuiru1)
1)Department of Hematology,Kaifeng Children's Hospital,Kaifeng,Henan 475000 2)Department of Pathology,Kaifeng Central Hospital,Kaifeng,Henan 475000 3)Department of Hematology,the Affiliated Tumor Hospital,Zhengzhou University,Zhengzhou 450003
关键词:
急性淋巴细胞白血病;  miR-100;  Nalm6细胞;  增殖;  侵袭;  迁移;  CXCR7/STAT3
Keywords:
acute lymphoblastic leukemia;  miR-100;  Nalm6 cell;  proliferation;  invasion;  migration;  CXCR7/STAT3
分类号:
R577
DOI:
10.13705/j.issn.1671-6825.2019.12.112
摘要:
目的:探究过表达miR-100对急性淋巴细胞白血病细胞增殖、侵袭与迁移的影响及其机制。方法:将Nalm6 细胞分为空白对照组、miR-100 NC组(转染阴性对照miR-100 NC)与 miR-100 mimic组(转染miR-100 mimic),qRT-PCR法检测各组细胞中miR-100表达变化,MTT法检测各组细胞转染第1、2、3、4 天时的增殖情况,Transwell小室法检测细胞的侵袭能力,细胞划痕实验检测细胞的迁移情况,Western blot法检测细胞中CXCR7、p-STAT3、STAT3、Cyclin D1、MMP-2和MMP-9蛋白水平,双荧光素酶报告实验检测miR-100与CXCR7基因的靶向关系。结果:与空白对照组和miR-100 NC组比较, miR-100 mimic组Nalm6细胞中miR-100的表达水平显著升高,转染第2、3和4天时Nalm6细胞的增殖能力显著降低,侵袭和迁移细胞数均减少,CXCR7、p-STAT3、Cyclin D1、MMP-2和MMP-9蛋白水平均显著下降(P<0.05)。TargetScan分析和双荧光素酶报告实验结果表明CXCR7可能是miR-100的靶基因,miR-100可显著抑制CXCR7野生型质粒的荧光素酶活性(P<0.05)。结论:过表达miR-100可抑制Nalm6细胞的增殖、侵袭和迁移,其机制可能与CXCR7/STAT3通路受到抑制相关。
Abstract:
Aim:To study the effects of miR-100 on proliferation,invasion and migration of acute lymphoblastic leukemia cells and its mechanism.Methods:Cultured Nalm6 cells were allocated into blank control group,miR-100 NC group(transfected negative control miR-100 NC)and miR-100 mimic group(transfected miR-100 mimic),the expression of miR-100 was detected by qRT-PCR.The proliferation of cells was detected at 1,2,3,and 4 days after transfection by MTT assay.The invasion ability of cells was detected by Transwell chamber method.The cell scratch test was used to detect migration ability.The expressions of CXCR7,p-STAT3,STAT3,Cyclin D1,MMP-2 and MMP-9 proteins were detected by Western blot.Dual luciferase reporter gene assay was used to detect the miR-100 and CXCR7 gene targeting.Results:Compared with the blank control group and the miR-100 NC group,the expression level of miR-100 in the miR-100 mimic group was significantly increased.The proliferative ability of Nalm6 cells was significantly decreased at 2,3 and 4 days after transfection,the number of invasion and migration cells was decreased,and the levels of CXCR7,p-STAT3,Cyclin D1,MMP-2 and MMP-9 proteins were significantly decreased(P<0.05).TargetScan analysis and dual luciferase reporter gene assay results indicated that CXCR7 may be a target gene of miR-100,and miR-100 significantly inhibited the luciferase activity level of CXCR7 wild-type plasmid(P<0.05).Conclusion:Overexpression of miR-100 can inhibit the proliferation,migration and invasion of Nalm6 cells,and its mechanism may be related to the inhibition of CXCR7/STAT3 pathway.

参考文献/References:

[1] IMAI K.Acute lymphoblastic leukemia:pathophysiology and current therapy[J].Rinsho Ketsueki,2017,58(5):460
[2] LARSON RA.Managing CNS disease in adults with acute lymphoblastic leukemia[J].Leuk Lymphoma,2018,59(1):3
[3] IACOBUCCI I,MULLIGHAN CG. Genetic basis of acute lymphoblastic leukemia[J].J Clin Oncol,2017,35:975
[4] ALDOSS I,GAAL K,AL MALKI MM,et al.Dasatinib-induced colitis after allogeneic stem cell transplantation for Philadelphia chromosome-positive acute lymphoblastic leukemia[J].Biol Blood Marrow Transplant,2016,22(10):1900
[5] 刘佳,江振洲,张陆勇.急性淋巴细胞白血病发病机制和药物研究进展[J].药物评价研究,2019,42(10):2100
[6] UEMURA S,NISHIMURA N,HASEGAWA D,et al.ETV6-ABL1 fusion combined with monosomy 7 in childhood B-precursor acute lymphoblastic leukemia[J].Int J Hematol,2018,107(5):604
[7] 陈楚言.白血病耐药性相关miRNAs作用的研究进展[J].世界最新医学信息文摘,2018,18(34):96
[8] BARTEL DP.MicroRNAs:genomics,biogenesis,mechanism,and function[J].Cell,2004,116(2):281
[9] SHEN Y,GONG JM,ZHOU LL,et al.Mir-451 as a new tumor marker for gastric cancer[J].Oncotarget,2017,8(34):56542
[10]李维娜,何飞.miR-140表达与肿瘤发生发展关系的研究进展[J].解放军医学杂志,2018,43(6):523
[11]ADLAKHA YK,SAINI N.Brain microRNAs and insights into biological functions and therapeutic potential of brain enriched miRNA-128[J].Mol Cancer,2014,13:33
[12]陈倩.miRNA在输血医学中的研究进展[J].中国输血杂志,2019,32(7):728
[13]DE CARVALHO IN,DE FREITAS RM,VARGAS FR.Translating microRNAs into biomarkers:What is new for pediatric cancer?[J].Med Oncol,2016,33(5):49
[14]LV M,ZHANG X,JIA H,et al.An oncogenic role of miR-142-3p in human T-cell acute lymphoblastic leukemia(T-ALL)by targeting glucocorticoid receptor-alpha and cAMP/PKA pathways[J].Leukemia,2012,26(4):769
[15]于万涛,王朝霞.miR-100与肿瘤关系的研究进展[J].临床肿瘤学杂志,2014,19(8):747
[16]QIN C,HUANG RY,WANG ZX.Potential role of miR-100 in cancer diagnosis,prognosis,and therapy[J].Tumor Biol,2015,36(3):1403
[17]AZIZMOHAMMADI S,AZIZMOHAMMADI S,SAFARI A,et al.The role and expression of miR-100 and miR-203 profile as prognostic markers in epithelial ovarian cancer[J].Am J Tansl Res,2016,8(5):2403
[18]于兰,杨云生.MicroRNAs在消化道疾病中的作用研究进展[J].解放军医学杂志,2013,38(12):1026
[19]CHEN P,ZHAO X,MA L.Downregulation of microRNA-100 correlates with tumor progression and poor prognosis in hepatocellular carcinoma[J].Mol Cell Biochem,2013,383(1/2):49
[20]FENG B,WANG R,CHEN LB.MiR-100 resensitizes docetaxel-resistant human lung adenocarcinoma cells(SPC-A1)to docetaxel by targeting Plk1[J].Cancer Lett,2012,317(2):184
[21]LABIB HA,ELANTOUNY NG,IBRAHIM NF,et al.Upregulation of microRNA-21 is a poor prognostic marker in patients with childhood B cell acute lymphoblastic leukemia[J].Hematology,2017,22(7):392
[22]ZHANG H,LUO XQ,ZHANG P,et al.MicroRNA patterns associated with clinical prognostic parameters and CNS relapse prediction in pediatric acute leukemia[J].PLoS One,2009,4(11):e7826
[23]GU J,ZHANG X,YANG Z,et al.Expression of Cyclin D1 protein isoforms and its prognostic significance in cervical cancer[J].Cancer Manag Res,2019,11:9073
[24]李晶,张蓉,赵力,等.单核细胞趋化蛋白-1诱导人主动脉平滑肌细胞表达基质金属蛋白酶-9及相关通路研究[J].解放军医学杂志,2012,37(5):464
[25]ROOMI MW,MONTERREY JC,KALINOVSKY T,et al.Patterns of MMP-2 and MMP-9 expression in human cancer cell lines[J].Oncol Rep,2009,21(5):1323
[26]LIU Z,TENG XY,MENG XP,et al.Expression of stromal cell-dervied factor 1 and CXCR7 ligand receptor system in pancreatic adenocarcinoma[J].World J Surg Oncol,2014,12:348
[27]LI W,DING Q,DING Y,et al.Oroxylin A reverses the drug resistance of chronic myelogenous leukemia cells to imatinib through CXCL12/CXCR7 axis in bone marrow microenvironment[J].Mol Carcinog,2017,56(3):863
[28]LI JT,JIA LT,LIU NN,et al.MiRNA-101 inhibits breast cancer growth and metastasis by targeting CX chemokine receptor 7[J].Oncotarget,2015,6(31):30818
[29]XIAO R,GAN M,JIANG T.Wogonoside exerts growth-suppressive effects against T acute lymphoblastic leuke-mia through the STAT3 pathway[J].Hum Exp Toxicol,2017,36(11):1169

备注/Memo

备注/Memo:
【基金项目】河南省医学科技重大攻关项目(201806031)
【作者简介】崔建坡,通信作者,男,1972年11月生,本科,副主任医师,研究方向:小儿血液疾病,E-mail:jianbo_cui@163.com
更新日期/Last Update: 2020-11-20