[1]吴江,张薇薇,李忠俊.lncRNA-TUG1促进放射后人骨髓间充质干细胞衰老[J].第三军医大学学报,2018,40(10):904-908.
 WU Jiang,ZHANG Weiwei,LI Zhongjun.Long noncoding RNA TUG1 promotes γ radiation-induced senescence of human bone marrow mesenchymal stem cells in vitro[J].J Third Mil Med Univ,2018,40(10):904-908.
点击复制

lncRNA-TUG1促进放射后人骨髓间充质干细胞衰老(/HTML )
分享到:

《第三军医大学学报》[ISSN:1000-5404/CN:51-1095/R]

卷:
40卷
期数:
2018年第10期
页码:
904-908
栏目:
基础医学
出版日期:
2018-05-30

文章信息/Info

Title:
Long noncoding RNA TUG1 promotes γ radiation-induced senescence of human bone marrow mesenchymal stem cells in vitro
作者:
吴江张薇薇李忠俊
陆军军医大学(第三军医大学)第二附属医院输血科
Author(s):
WU Jiang ZHANG Weiwei LI Zhongjun

Department of Blood Transfusion, Second Affiliated Hospital, Army Medical University (Third Military Medical University), Chongqing, 400037, China

关键词:
lncRNA-TUG1骨髓间充质干细胞放射
Keywords:
LncRNA-TUG1 bone marrow mesenchymal stem cells &gamma radiation
分类号:
R329.2;R818.023;R818.74
文献标志码:
A
摘要:

目的    探讨lncRNA-TUG1在放射导致的骨髓间充质干细胞(bone marrow mesenchymal stem cells, BMMSCs)衰老中所起的作用。方法    实验分为lncRNA-TUG1干扰组、lncRNA-TUG1对照组,用γ射线造成放射损伤后,采用实时荧光定量PCR(RT-PCR)检测lncRNA-TUG1在2组的表达变化,采用Western blot检测2组的γ-H2AX蛋白反映DNA损伤,检测衰老相关蛋白p53表达以及β-半乳糖苷酶染色反映细胞衰老。结果γ    射线放射显著增加了BM-MSCs中lncRNA-TUG1表达(P<0.01),BM-MSCs中迅速出现γ-H2AX磷酸化,p53蛋白水平升高,BM-MSCs衰老明显增加;而干扰lncRNA-TUG1后,放射后BM-MSCs的DNA损伤修复加快,p53蛋白水平下降,细胞衰老明显减少(P<0.01)。结论    放射可能通过lncRNA-TUG1促进BM-MSCs的衰老。

Abstract:

Objective     To study the role of long noncoding RNA TUG1 (LncRNA-TUG1) in γ radiation-induced senescence of human bone marrow mesenchymal stem cells (BM-MSCs) in vitro. Methods    Human BMMSCs were transfected with a lentiviral vector carrying short-hairpin RNA (shRNA) targeting LncRNATUG1 (LncRNA-TUG1-SI) or with an empty lentiviral vector prior to γ-ray radiation. Cell senescence following the exposure was analyzed using SA-β-Gal staining, and Western blotting was used to detect the changes in the expressions of γ-H2AX (an indicator of DNA double-strand breaks) and p53 in the cells. Results    γ-ray radiation at 9 Gy resulted in rapid γ-H2AX phosphorylation, significantly increased cell senescence, and increased protein levels enhanced expression of p53 and the expression of LncRNA-TUG1 in human BMMSCs. In contrast, BM-MSCs transfected with LncRNA-TUG1 shRNA showed a fast recovery from γ radiation-induced DNA damage with significantly reduced cell senescence and decreased protein levels of p53. Conclusions    LncRNA-TUG1 may promote senescence of BM-MSCs following γ radiation and can serve as a potential target for intervention of radiation-induced senescence of BM-MSCs.

参考文献/References:

[1]FLIEDNER T M, CHAO N J, BADER J L, et al. Stem cells, multiorgan failure in radiation emergency medical preparedness: a U.S./European Consultation Workshop[J]. Stem Cells, 2009, 27(5): 1205-1211. DOI: 10.1002/stem.16.
[2]BIANCO P. “Mesenchymal” stem cells[J]. Annu Rev Cell Dev Biol, 2014, 30: 677-704. DOI: 10.1146/annurevcellbio100913013132.
[3]NICOLAY N H, LOPEZ PEREZ R, SAFFRICH R, et al. Radioresistant mesenchymal stem cells: mechanisms of resistance and potential implications for the clinic[J]. Oncotarget, 2015, 6(23): 19366-19380. DOI: 10.18632/oncotarget.4358.
[4]CHEN L, RAN Q, XIANG Y, et al. Coactivation of PKCδ by CRIF1 modulates oxidative stress in bone marrow multipotent mesenchymal stromal cells after irradiation by phosphorylating NRF2 Ser40[J]. Theranostics, 2017, 7(10): 2634-2648. DOI: 10.7150/thno.17853.
[5]ZHANG X, XIANG L, RAN Q, et al. Crif1 promotes adipogenic differentiation of bone marrow mesenchymal stem cells after irradiation by modulating the PKA/CREB signaling pathway[J]. Stem Cells, 2015, 33(6): 1915-1926. DOI: 10.1002/stem.2019.
[6]DOMINICI M, LE BLANC K, MUELLER I, et al. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement[J]. Cytotherapy, 2006, 8(4): 315-317. DOI: 10.1080/14653240600855905.
[7]LI X, WU Z, FU X, et al. Long noncoding RNAs: insights from biological features and functions to diseases[J]. Med Res Rev, 2013, 33(3): 517-553. DOI: 10.1002/med.21254.
[8]YOUNG T L, MATSUDA T, CEPKO C L. The noncoding RNA taurine upregulated gene 1 is required for differentiation of the murine retina[J]. Curr Biol, 2005, 15(6): 501-512. DOI: 10.1016/j.cub.2005.02.027.
[9]ZHANG E B, YIN D D, SUN M, et al. P53regulated long noncoding RNA TUG1 affects cell proliferation in human nonsmall cell lung cancer, partly through epigenetically regulating HOXB7 expression[J]. Cell Death Dis, 2014, 5: e1243. DOI: 10.1038/cddis.2014.201.
[10]ISIN M, OZGUR E, CETIN G, et al. Investigation of circulating lncRNAs in Bcell neoplasms[J]. Clin Chim Acta, 2014, 431: 255-259. DOI: 10.1016/j.cca.2014.02.010.
[11]HUANG M D, CHEN W M, QI F Z, et al. Long noncoding RNA TUG1 is upregulated in hepatocellular carcinoma and promotes cell growth and apoptosis by epigenetically silencing of KLF2[J]. Mol Cancer, 2015, 14: 165. DOI: 10.1186/s1294301504310.
[12]LIU Q, SUN S, YU W, et al. Altered expression of long noncoding RNAs during genotoxic stressinduced cell death in human glioma cells[J]. J Neurooncol, 2015, 122(2): 283-292. DOI: 10.1007/s1106001517180.
[13]XU Y, WANG J, QIU M, et al. Upregulation of the long noncoding RNA TUG1 promotes proliferation and migration of esophageal squamous cell carcinoma[J]. Tumour Biol, 2015, 36(3): 1643-1651. DOI: 10.1007/s1327701427636.
[14]MA B, LI M, ZHANG L, et al. Upregulation of long noncoding RNA TUG1 correlates with poor prognosis and disease status in osteosarcoma[J]. Tumour Biol, 2016, 37(4): 4445-4455. DOI: 10.1007/s1327701543016.

相似文献/References:

[1]李茂华,滕苗.严重烧伤大鼠血清对骨髓间充质干细胞迁移的影响[J].第三军医大学学报,2015,37(16):1643.
 Li Maohua,Teng Miao.Serum from severely burned rats promotes migration in rat bone marrow mesenchymal stem cells through PI3K/Akt signal pathway[J].J Third Mil Med Univ,2015,37(10):1643.
[2]张蕾,陈沅,田杰,等.心肌细胞介导骨髓间充质干细胞的心肌样分化[J].第三军医大学学报,2005,27(16):1681.
[3]王颖楠,范雪梅,赵敏,等.脱细胞膀胱基质复合大鼠骨髓间充质干细胞体外构建组织工程化吊带治疗压力性尿失禁的初步研究[J].第三军医大学学报,2012,34(22):2269.
 Wang Yingnan,Fan Xuemei,Zhao Min,et al.Preliminary study on the construction of a tissue-engineered sling with BMSCs and UBM in vitro for treating stress urinary incontinence[J].J Third Mil Med Univ,2012,34(10):2269.
[4]周长立,任先军,蒋涛,等.Wnt7a基因对大鼠骨髓间充质干细胞增殖及向神经元样细胞分化的影响[J].第三军医大学学报,2013,35(08):702.
 Zhou Changli,Ren Xianjun,Jiang Tao,et al.Wnt7a gene stimulates mesenchymal stem cell proliferation and differentiation into neuron-like cells[J].J Third Mil Med Univ,2013,35(10):702.
[5]郝磊,邹仲敏,王军平,等.hPDGF-A/hBD2双基因共表达腺病毒载体的构建及表达[J].第三军医大学学报,2007,29(10):859.
 HAO Lei,ZOU Zhong-min,WANG Jun-ping,et al.Construction and identification of recombinant adenovirus expressing hPDGF-A and hBD2[J].J Third Mil Med Univ,2007,29(10):859.
[6]郭书权,吴雪晖,许建中,等.两种方法分离小型猪骨髓间充质干细胞的比较[J].第三军医大学学报,2007,29(10):988.
[7]黄文秋,黄宏,徐祥,等.mTOR及其下游信号通路在骨髓间充质干细胞氧化应激损伤中的变化及作用[J].第三军医大学学报,2013,35(02):114.
 Huang Wenqiu,Huang Hong,Xu Xiang,et al.Changes and roles of mTOR and its downstream signaling passway in mouse bone marrow stem cells with oxidative stress injury[J].J Third Mil Med Univ,2013,35(10):114.
[8]冯一梅,徐辉,邹仲敏,等.hPDGF-A/hBD2双基因转染对大鼠骨髓间充质干细胞生物学特性的影响[J].第三军医大学学报,2008,30(06):472.
 FENG Yi-mei,XU Hui,ZOU Zhong-min,et al.Effects of hPDGF-A/hBD2 genes transfection on rat bone marrow mesenchymal stem cells[J].J Third Mil Med Univ,2008,30(10):472.
[9]姚青,宋治远,马显光.脉冲微交流电刺激促进体外诱导大鼠骨髓间充质干细胞向心肌分化[J].第三军医大学学报,2008,30(05):410.
 YAO Qing,SONG Zhi-Yuan,MA Xian-guang.Electrical stimulation promotes the differentiation of rat bone marrow mesenchymal stem cells to cardiomyocyte induced by 5-azacytidine in vitro[J].J Third Mil Med Univ,2008,30(10):410.
[10]朱淑霞,李永华,宋治远,等.电磁场促进骨髓间充质干细胞体外诱导分化时细胞增殖[J].第三军医大学学报,2008,30(05):421.
 ZHU Shu-xia,LI Yong-hua,SONG Zhi-yuan,et al.Pulsed electromagnetic fields improve proliferation of rat marrow mesenchymal stem cells induced by 5-azacytidine[J].J Third Mil Med Univ,2008,30(10):421.

更新日期/Last Update: 2018-05-30