[1]代朦,靳鑫,雷优扬,等.过表达miR-382的肿瘤相关巨噬细胞对三阴性乳腺癌生物学特性的影响[J].第三军医大学学报,2018,40(15):1375-1382.
 DAI Meng,JIN Xin,LEI Youyang,et al.Effect of miR-382 overexpressing tumor-associated macrophages on biological properties of triple-negative breast cancer 4T1 cells [J].J Third Mil Med Univ,2018,40(15):1375-1382.
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过表达miR-382的肿瘤相关巨噬细胞对三阴性乳腺癌生物学特性的影响(/HTML )
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《第三军医大学学报》[ISSN:1000-5404/CN:51-1095/R]

卷:
40卷
期数:
2018年第15期
页码:
1375-1382
栏目:
基础医学
出版日期:
2018-08-15

文章信息/Info

Title:
Effect of miR-382 overexpressing tumor-associated macrophages on biological properties of triple-negative breast cancer 4T1 cells
 
作者:
代朦靳鑫雷优扬明佳
重庆医科大学附属第二医院三腺外科
Author(s):
DAI Meng JIN Xin LEI Youyang MING

Department of Three Gland Surgery, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China

关键词:
三阴性乳腺癌巨噬细胞microRNA-382生物学特性  
Keywords:
triple-negative breast cancer macrophages microRNA-382 biological properties
分类号:
R394.3; R730.23; R737.9
文献标志码:
A
摘要:

目的     探讨microRNA-382(miR-382)在肿瘤相关巨噬细胞(tumor-associated macrophages,TAMs)中的表达对三阴性乳腺癌(triplenegative breast cancer,TNBC)细胞(4T1)生物学特性的影响。 方法    以小鼠腹腔巨噬细胞(mouse peritoneal macrophages,PMs)作为研究对象,分为PMs组,TAMs组和L-TAMs组;Western blot与qRT-PCR检测极化指标(IL-10、TNF-α)、miR-382、PGC1α和NF-κB的表达变化;流式细胞术检测TAMs的极化变化(CD86、CD206);激光共聚焦显微镜成像检测PGC-1α和NF-κB的表达变化;以4T1细胞作为研究对象,分为4T1组,4T1+PMs组和4T1+L-PMs组,流式细胞术检测细胞凋亡率与细胞周期;Transwell侵袭实验检测细胞侵袭能力。 结果   与PMs组比较,TAMs组IL-10、CD206和PGC-1α表达明显增加(P<0.05),miR-382、TNF-α和CD86表达明显降低(P<0.05),NF-κB转录活性显著降低(P<0.05),而L-TAMs组TNF-α、CD86和miR-382表达明显增高(P<0.05),IL-10、CD206和PGC-1α表达明显降低(P<0.05),NF-κB转录活性显著增强(P<0.05);与4T1组比较,4T1+PMs组侵袭能力明显增强(P<0.05),凋亡率明显下降(P<0.05),而4T1+LPMs组侵袭能力明显下降(P<0.05),凋亡率明显增高(P<0.05)。 结论    TAMs通过调节miR-382的表达可抑制TNBC的侵袭和增殖,其机制可能与TAMs中miR-382抑制PGC-1α的表达、增强NF-κB的转录活性,进而抑制TAMs的M2分化有关。
 

Abstract:

Objective     To investigate the effect of microRNA-382 (miR-382) in tumorassociated macrophages (TAMs) on the biological characteristics of triplenegative breast cancer cells in vitro. Methods     Mouse peritoneal macrophages (PMs) were used as research subjects and divided into PMs group, TAMs group and L-TAMs group (miR-382 overexpressing PMs cocultured with 10%TAM in a Transwell chamber system). Western blotting and qRT-PCR were used to detect the markers of polarization (IL-10, TNF-α) and the expression changes of miR-382, PGC-1α and NF-κB. Flow cytometry was employed to determine the polarization changes of TAMs (CD86, CD206), and laser confocal microscopy to observe the expression of PGC-1α and NF-κB. Triple-negative breast cancer cells 4T1 were divided into 4T1 group, 4T1+PMs co-culture group and 4T1+LPMs co-culture group. Flow cytometry was adopted to detect the apoptotic rate and cell cycle. Transwell invasion assay was used to measure the invasion ability of  the cells. Results     Compared with the PMs group, the expression of IL-10, CD206 and PGC-1α was increased (P<0.05), and that of TNF-α, CD86 and miR382 was decreased (P<0.05), transcriptional activity of NF-κB was reduced (P<0.05) in the TAMs group; While in the L-TAMs, the results were totally opposite to those in the PMs group (P<0.05). Compared with the 4T1 group, the invasive ability of 4T1+PMs group was increased (P<0.05) and the apoptotic rate was decreased (P<0.05), while the invasive ability was lowered (P<0.05) and the apoptotic rate was enhanced (P<0.05) in the 4T1+L-PMs group. Conclusion     TAMs inhibit the invasion and proliferation of triple-negative breast cancer by regulating the expression of miR-382, which may be related to the inhibition of the expression of PGC-1α by miR-382, the transcriptional activity of NF-κB and the inhibition of M2 differentiation of TAMs.
 

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更新日期/Last Update: 2018-08-19