MiRNA Let-7a及miR-34a与氯化镧抑制宫颈癌淋巴转移作用的相关性研究
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摘要
目的探究miRNA Let-7a及miR-34a与氯化镧抑制宫颈癌淋巴转移作用的相关性。方法应用宫颈癌U14荷瘤小鼠,随机分为对照组及给药组,给药组小鼠给予氯化镧(含氯化镧2mg/kg),连续灌胃14d后,解剖检查并根据淋巴转移程度进行等级评分,应用逆转录实时荧光定量PCR分别检测两组小鼠宫颈组织中Let-7a及miR-34a的表达,并与淋巴转移等级进行相关性研究。结果给药组与对照组相比,宫颈癌组织MiRNA Let-7a及miR-34a的水平显著上调,宫颈癌转移程度有所缓解,且Let-7a及miR-34a与小鼠淋巴转移等级呈正相关变化,差异具有显著性(P<0.05)。结论氯化镧通过增加Let-7a及miR-34a的表达,抑制宫颈癌荷瘤小鼠淋巴转移程度,且Let-7a及miR-34a的水平变化能够作为氯化镧药理作用的分子标记物,为临床研究提供潜在的治疗靶点及诊断指标。
Objective To explore the correlation between miRNA Let-7 a,miR-34 aand lanthanum chloride in the inhibition of lymph node metastasis of cervical cancer.Methods U14 tumor-bearing mice of cervical cancer were randomly divided into control group and medicated group.Medicated group was given 2 mg/kg of lanthanum chloride,and then dissected after 14 dof continuous intragastric administration,and graded according to the degree of lymphatic metastasis.The expression of Let-7 aand miR-34 ain cervix tissues were detected by real-time fluorescent quantitative reverse transcription PCR in the two groups,and its correlation with lymph node metastasis grade was studied.Results Compared with control group,the levels of MiRNA Let-7 aand miR-34 ain cervix tissues were significantly up-regulated in medicated group,and the degree of cervical cancer metastasis was relieved,and the levels of Let-7 aand miR-34 awere positively correlated with lymph node metastasis grade in mice(P<0.05).Conclusions Lanthanum chloride can inhibit the degree of lymph node metastasis of cervical cancer-bearing mice by increasing the expression of Let-7 aand miR-34 a,and the changes of levels of Let-7 aand miR-34 acan be used as molecular markers for the pharmacological effects of lanthanum chloride so as to provide potential therapeutic targets and diagnostic indicators for clinical research.
Objective To explore the correlation between miRNA Let-7 a,miR-34 aand lanthanum chloride in the inhibition of lymph node metastasis of cervical cancer.Methods U14 tumor-bearing mice of cervical cancer were randomly divided into control group and medicated group.Medicated group was given 2 mg/kg of lanthanum chloride,and then dissected after 14 dof continuous intragastric administration,and graded according to the degree of lymphatic metastasis.The expression of Let-7 aand miR-34 ain cervix tissues were detected by real-time fluorescent quantitative reverse transcription PCR in the two groups,and its correlation with lymph node metastasis grade was studied.Results Compared with control group,the levels of MiRNA Let-7 aand miR-34 ain cervix tissues were significantly up-regulated in medicated group,and the degree of cervical cancer metastasis was relieved,and the levels of Let-7 aand miR-34 awere positively correlated with lymph node metastasis grade in mice(P<0.05).Conclusions Lanthanum chloride can inhibit the degree of lymph node metastasis of cervical cancer-bearing mice by increasing the expression of Let-7 aand miR-34 a,and the changes of levels of Let-7 aand miR-34 acan be used as molecular markers for the pharmacological effects of lanthanum chloride so as to provide potential therapeutic targets and diagnostic indicators for clinical research.
引文
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[3]田玉旺,许春伟,方美玉.宫颈癌、子宫内膜癌及卵巢癌中全基因组关联分析计量研究[J].贵州医药,2014,38(6):491-494.
[4]王宇华,原杰彦,杨宾烈,等.宫颈癌NOB1的表达及其与HPV感染及预后的关系分析[J].临床和实验医学杂志,2017,16(8):762-765.
[5]Voorhoeve P M,Sage C L,Schrier M,et al.A genetic screen implicates miRNA-372and miRNA-373as oncogenes in testicular germ cell tumors[J].Advances in Experimental Medicine&Biology,2007,604(6):17.
[6]汤文凡,刘朝奇,佐满珍.miRNA在宫颈癌早期诊断中的应用及其价值探讨[J].实用医学杂志,2012,28(1):30-32.
[7]汤文凡,佐满珍,刘朝奇.miRNA在宫颈癌早期诊断中的应用及其价值探讨[C].中国抗癌协会妇科肿瘤专业委员会全国学术会议,2011,30-32.
[8]甘自立,谌模武,林红,等.NF-κB及其调控的miRNA在宫颈癌移植瘤及癌旁组织中的活化和表达[J].基础医学与临床,2014,34(1):1-5.
[9]俞玲芳,陈宏伟,汪泱,等.镧抑制内毒素/脂多糖激活NF-κB信号通路的分子机制探讨[J].中华微生物学和免疫学杂志,2011,31(12):1057-1062.
[10]娄远蕾.镧抑制脂多糖诱导小鼠巨噬细胞产生一氧化氮的机制[D].南昌大学医学院南昌大学,2007.
[11]闫晓明,于伟东,洪新雨,等.氯化镧抑制人脑胶质瘤SHG44细胞增殖及作用机制研究[J].中国实验诊断学,2006,10(4):361-363.
[12]王芃,黄健,张天蓝,等.氯化镧抑制前列腺癌细胞DU145的生长和迁移[J].科学通报,2010,55(23):2289-2295.
[13]苗政,张福泉.宫颈癌放射治疗进展[J].中国肿瘤临床,2017,44(18):899-902.
[14]郭菲,汪泱,李国辉.稀土镧化合物抑制TNF-α活化NF-κB信号通路[C].中华医学会烧伤外科学分会2009年学术年会,2009.
[15]李开璇,季小琳,孙诚,等.抑制JNK活性对HepG2细胞胰岛素信号通路的影响[J].中华内分泌代谢杂志,2017,33(2):129-134.
[16]Sampson V B,Rong N H,Han J,et al.MicroRNA let-7adown-regulates MYC and reverts MYC-induced growth in Burkitt lymphoma cells[J].Cancer Research,2007,67(20):9762.
[17]Meng F,Henson R,Wehbe-Janek H,et al.The MicroRNA let-7a modulates interleukin-6-dependent STAT-3 survival signaling in malignant human cholangiocytes[J].Journal of Biological Chemistry,2007,282(11):8256.
[18]Chang T C,Wentzel E A,Kent O A,et al.Transactivation of miR-34aby p53broadly influences gene expression and promotes apoptosis[J].Molecular Cell,2007,26(5):745.
[19]Tazawa H,Tsuchiya N,Izumiya M,et al.Tumor-suppressive miR-34ainduces senescence-like growth arrest through modulation of the E2Fpathway in human colon cancer cells[J].Proceedings of the National Academy of Sciences of the United States of America,2007,104(39):15472.