miR-34c-3p与M2型肿瘤相关巨噬细胞在三阴性乳腺癌中的表达及意义
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摘要
目的:检测miR-34c-3p与M2型肿瘤相关巨噬细胞(tumor-associated macrophage,TAM)在三阴性乳腺癌(triple negative breast cancer,TNBC)中的表达,并探讨其在乳腺癌发病中的意义。方法:选择2017年2月至2018年1月于西京医院就诊的68例TNBC患者作为实验组(A组),以同期就诊的70例乳腺纤维腺瘤患者作为对照组(B组)。采用Real-time RT-PCR检测组织标本中miR-34c-3p的表达;流式细胞检测M2型TAM的表达; ELISA法检测血清中IL-10的表达。并进一步分析miR-34c-3p的表达与乳腺癌M2型TAM及血清IL-10水平的相关性。结果:A、B组miR-34c-3p的相对表达量分别为0. 84±0. 08、1. 29±0. 71,A组明显低于B组,差异有统计学意义(P <0. 05)。与B组比较,A组M2型TAM(CD68+CD163+)细胞比例显著升高(P <0. 05)。A组血清IL-10的表达[(19. 69±4. 93) pg/ml]较B组[(17. 26±3. 51) pg/ml]显著升高,差异有统计学意义(P <0. 05)。TNBC组织中miR-34c-3p的表达与M2型TAM比例及血清IL-10表达均呈显著负相关(r=-0. 508,r=-0. 656,P <0. 05)。结论:TNBC组织中miR-34c-3p的表达下调,M2型TAM比例及血清IL-10表达均显著升高,促进TNBC进展。
Objective: To detect the expression of miR-34 c-3 p and M2 type of tumor-associated macrophage( TAM) in triple negative breast cancer( TNBC) patients and explore their significance in the pathogenesis of breast cancer. Methods: All 68 TNBC patients in Xijing Hospital from February 2017 to January 2018 were selected as the experimental group( group A),and 70 breast fibroadenoma patients in the same period were treated as the control group( group B). Real-time RT-PCR was used to detect the expression of miR-34 c-3 p. M2 type of TAM expression was detected by flow cytometry. The expression of IL-10 in serum was detected by ELISA. To analyze of the correlation between miR-34 c-3 p and M2 type of TAM and IL-10. Results: miR-34 c-3 p in group A was significantly lower than that in group B,and the relative expression level was 0. 84 ± 0. 08,1. 29 ± 0. 71 respectively,and the difference was statistically significant( P < 0. 05). Compared with group B,the proportion of M2 type of TAM in group A( CD6 8+CD1 6 3+) was increased significantly( P < 0. 05). The expression of IL-10 in group A [( 19. 69± 4. 93) pg/ml]was significantly higher than that in group B [( 17. 26 ± 3. 51) pg/ml]( P < 0. 05). The expression of miR-34 c-3 p in TNBC tissues was negatively correlated with the ratio of M2 type of TAM and serum IL-10 level( r =-0. 508,r =-0. 656,P < 0. 05). Conclusion: The expression of miR-34 c-3 p in TNBC tissues was down-regulated,and the proportion of M2 type of TAM and serum IL-10 expression were significantly elevated,which contributed to the progression of TNBC.
Objective: To detect the expression of miR-34 c-3 p and M2 type of tumor-associated macrophage( TAM) in triple negative breast cancer( TNBC) patients and explore their significance in the pathogenesis of breast cancer. Methods: All 68 TNBC patients in Xijing Hospital from February 2017 to January 2018 were selected as the experimental group( group A),and 70 breast fibroadenoma patients in the same period were treated as the control group( group B). Real-time RT-PCR was used to detect the expression of miR-34 c-3 p. M2 type of TAM expression was detected by flow cytometry. The expression of IL-10 in serum was detected by ELISA. To analyze of the correlation between miR-34 c-3 p and M2 type of TAM and IL-10. Results: miR-34 c-3 p in group A was significantly lower than that in group B,and the relative expression level was 0. 84 ± 0. 08,1. 29 ± 0. 71 respectively,and the difference was statistically significant( P < 0. 05). Compared with group B,the proportion of M2 type of TAM in group A( CD6 8+CD1 6 3+) was increased significantly( P < 0. 05). The expression of IL-10 in group A [( 19. 69± 4. 93) pg/ml]was significantly higher than that in group B [( 17. 26 ± 3. 51) pg/ml]( P < 0. 05). The expression of miR-34 c-3 p in TNBC tissues was negatively correlated with the ratio of M2 type of TAM and serum IL-10 level( r =-0. 508,r =-0. 656,P < 0. 05). Conclusion: The expression of miR-34 c-3 p in TNBC tissues was down-regulated,and the proportion of M2 type of TAM and serum IL-10 expression were significantly elevated,which contributed to the progression of TNBC.
引文
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[23]Komohara Y,Takeya M.CAFs and TAMs:Maestros of the tumour microenvironment[J].J Pathol,2017,241(3):313-315.
[24]Bolli Evangelia,Movahedi Kiavash,Laoui Damya,et al.Novel insights in the regulation and function of macrophages in the tumor microenvironment[J].Curr Opin Oncol,2017,29(1):55-61.
[25]Chen Varol,Alexander Mildner,Steen Jung.Macrophages:Development and tissue specialization[J].Ann Rev Immunol,2015,33:643-675.
[26]Wei Chong,Jiang Zhichao,Wang Haotian,et al.Lenalidomide significantly inhibits the differentiation of monocytes to M2 polarized macrophages and down-regulates secretion of associated cytokines[J].Basic&Clinical Medicine,2015,35(6):786-791.[魏冲,姜志超,王昊天,等.来那度胺可抑制单核细胞向M2型巨噬细胞分化及相关细胞因子的分泌[J].基础医学与临床,2015,35(6):786-791.]
[2]Torre LA,Bray F,Siegel RL,et al.Global cancer statistics,2012[J].CA Cancer J Clin,2015,65(2):87-108.
[3]Cao Mingli,Song Fengju.Advances in breast cancer epidemiology based on molecular subtyping[J].Chin J Clin Oncol,2017,44(9):449-451.[曹明丽,宋丰举.基于分子分型的乳腺癌流行病学新认识[J].中国肿瘤临床,2017,44(9):449-451.]
[4]Du Danyu,Ai Xiongfei,Li Yao,et al.The role of lactate-a tumor microenvironmental stress factor in cancer development[J].Progress Modern Biomed,2016,16(15):2987-2989.[杜丹玉,艾雄飞,李瑶,等.肿瘤微环境应激因子乳酸在肿瘤发展中的作用[J].现代生物医学进展,2016,16(15):2987-2989.]
[5]Liu Y,Cao X.The origin and function of tumor-associated macrophages[J].Cell Mol Immunol,2015,12(1):1-4.
[6]Steiner JL,Davis JM,Mc Clellan JL,et al.Effects of the MCP-1synthesis inhibitor bindarit on tumorigenesis and inflammatory markers in the C3(1)/SV40Tag mouse model of breast cancer[J].Cytokine,2014,66(1):60-68.
[7]Zhang Xinming,Sun Fengbo.Research advances of tumor-associated macrophages in tumor progression[J].Modern Oncology,2017,25(18):3008-3011.[张新明,孙风波.肿瘤相关巨噬细胞对肿瘤促进作用的研究进展[J].现代肿瘤医学,2017,25(18):3008-3011.]
[8]Li Hai,Che Jing,Wu Yi,et al.Effects of microRNA regulatory network on tumor associated macrophage differentiation and function in breast cancer and the action mechanism[J].Chinese J Exp Surg,2016,33(4):929-932.
[9]Liu Xiangyan,Feng Jie,Tang Lili,et al.The regulation and function of miR-21-FOXO3a-miR-34b/c signaling in breast cancer[J].Int J Mol Sci,2015,16(2):3148-3162.
[10]Dong YS,Hou WG,Li Y,et al.Unexpected requirement for a binding partner of the syntaxin family in phagocytosis by murine testicular Sertoli cells[J].Cell Death and Differentiation,2016,23(5):787-800.
[11]Kwan ML,Bernard PS,Kroenke CH,et al.Breast feeding,PAM50tumor subtype,and breast cancer prognosis and survival[J].JNatl Cancer Inst,2015,107(7):087.
[12]Zhao Yan,Sun Yali,Nie Xin.The characteristics of gene,pathology and imaging manifestations in triple-negative breast cancer[J].Modern Oncology,2016,24(16):2656-2659.[赵妍,孙雅丽,聂鑫.三阴性乳腺癌的基因、蛋白表达特点及病理、影像学表现[J].现代肿瘤医学,2016,24(16):2656-2659.]
[13]Hu Yanping,Wu Ying,Wei Li,et al.Expression of microRNA-34c-5p in laryngeal epithelial premalignant lesions and clinicopathological analysis[J].Chinese Archives of OtolaryngologyHead and Neck Surgery,2015,22(8):405-410.
[14]Cai KM,Bao XL,Kong XH,et al.Hsa-miR-34c suppresses growth and invasion of human laryngeal carcinoma cells via targeting c-Met[J].Int J Mol Med,2010,25:565-571.
[15]Gao Ning,Xia Ying,Jin Hu,et al.Mechanism of miR-34c-3p regulating proliferation,differentiation and apoptosis of glioma cells[J].Chin J Ctrl Endem Dis,2016,31(12):1386-1387.[高宁,夏鹰,金虎,等.miR-34c-3p调控脑胶质瘤细胞增殖、分化、凋亡的机制研究[J].中国地方病防治杂志,2016,31(12):1386-1387.]
[16]Yang S,Li WS,Dong F,et al.KITLG is a novel target of miR-34c that is associated with the inhibition of growth and invasion in colorectal cancer cells[J].J Cell Mol Med,2014,18(10):2092-2102.
[17]Xiao CZ,Wei W,Guo ZX,et al.MicroRNA-34c-3p promotes cell proliferation and invasion in hepatocellular carcinoma by regulation of NCKAP1 expression[J].J Cancer Res Clin Oncol,2017,143(2):263-273.
[18]Wu Jiang,Li Weizhi,Huang Meiling,et al.Regulation of cancerous progression and epithelial-mesenchymal transition by miR-34c-3p via modulation of MAP3K2 signaling in triple-negative breast cancer cells[J].Biochem Biophys Res Commun,2017,483(1):10-16.
[19]Davies LC,Taylor PR.Tissue-resident macrophages:Then and now[J].Immunology,2015,144(4):541-548.
[20]Mills CD.Anatomy of a discovery:m1 and m2 macrophages[J].Front Immunol,2015,6:212.
[21]Rhee I.Diverse macrophages polarization in tumor microenvironment[J].Arch Pharm Res,2016,39(11):1588-1596.
[22]Zhou SL,Zhou ZJ,Hu ZQ,et al.Tumor-associated neutrophils recruit macrophages and T-regulatory cells to promote progression of hepatocellular carcinoma and resistance to sorafenib[J].Gastroenterology,2016,150(7):1646-1658.
[23]Komohara Y,Takeya M.CAFs and TAMs:Maestros of the tumour microenvironment[J].J Pathol,2017,241(3):313-315.
[24]Bolli Evangelia,Movahedi Kiavash,Laoui Damya,et al.Novel insights in the regulation and function of macrophages in the tumor microenvironment[J].Curr Opin Oncol,2017,29(1):55-61.
[25]Chen Varol,Alexander Mildner,Steen Jung.Macrophages:Development and tissue specialization[J].Ann Rev Immunol,2015,33:643-675.
[26]Wei Chong,Jiang Zhichao,Wang Haotian,et al.Lenalidomide significantly inhibits the differentiation of monocytes to M2 polarized macrophages and down-regulates secretion of associated cytokines[J].Basic&Clinical Medicine,2015,35(6):786-791.[魏冲,姜志超,王昊天,等.来那度胺可抑制单核细胞向M2型巨噬细胞分化及相关细胞因子的分泌[J].基础医学与临床,2015,35(6):786-791.]