MicroRNA-155, induced by FOXP3 through transcriptional repression of BRCA1, is associated with tumor initiation in human breast cancer.
MicroRNA-155, induced by FOXP3 through transcriptional repression of BRCA1, is associated with tumor initiation in human breast cancer.
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MicroRNA-155 由 FOXP3 通过 BRCA1 转录抑制诱导，与人类乳腺癌的肿瘤发生相关
DOI：
10.18632/oncotarget.17816
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发表时间：
2017-06-20
期刊：
影响因子：
--
通讯作者：
Liu R
中科院分区：
文献类型：
--
作者：
Gao S;Wang Y;Wang M;Li Z;Zhao Z;Wang RX;Wu R;Yuan Z;Cui R;Jiao K;Wang L;Ouyang L;Liu R
MicroRNA（miR）-155在乳腺癌细胞和乳腺癌患者血清中上调，但其临床相关性仍不确定。本工作的目的是解决miR-155的转录调控。对公共数据集的生物信息学分析验证了乳腺癌患者肿瘤细胞中miR-155的上调，特别是那些处于早期阶段并患有三阴性癌症的患者。肿瘤细胞和血细胞中miR-155的表达谱和临床相关性通过TaqMan miR测定进行表征，血浆和外泌体中通过巢式定量PCR分析进行表征。FOXP 3和miR-155在乳腺癌细胞系和原发性乳腺癌中的表达呈正相关。在乳腺癌细胞中，FOXP 3通过BRCA 1的转录抑制诱导miR-155。此外，在亚拉巴马队列中，从259名参与者中收集血液和血浆样本，包括乳腺癌或良性乳腺肿瘤患者，乳腺癌家族成员和匹配的健康女性对照。对于早期或局限性乳腺癌患者，血浆和血细胞中的miR-155水平均较高。在培养的乳腺癌细胞中，miR-155的表达被FOXP 3诱导，但在培养基或外泌体中没有显著变化，这表明循环miR-155来源于血细胞。这些发现揭示了乳腺癌细胞中FOXP 3-BRCA 1-miR-155的转录轴，并表明血浆miR-155可作为检测早期乳腺癌的非侵入性生物标志物。
MicroRNA (miR)-155 is upregulated in breast cancer cells and in sera of patients with breast cancer, but its clinical relevance remains uncertain. The objective of the present effort was to address the transcriptional regulation of miR-155. A bioinformatics analysis of public datasets validated upregulation of miR-155 in tumor cells of patients with breast cancer, particularly those who were at early stages and had triple-negative cancers. The expression profiling and clinical relevance of miR-155 in tumor cells and blood cells were characterized by TaqMan miR assays and, in plasma and exosomes, by nest-quantitative PCR analysis. There was a positive correlation between expression of FOXP3 and miR-155 in breast cancer cell lines and primary breast cancers. In breast cancer cells, FOXP3 induced miR-155 through transcriptional repression of BRCA1. Furthermore, in an Alabama cohort, blood and plasma samples were collected from 259 participants, including patients with breast cancer or benign breast tumors, members of breast cancer families, and matched healthy female controls. For patients with early stage or localized breast cancer, there were high levels of miR-155 in both plasma and blood cells. In cultured breast cancer cells, expression of miR-155 was induced by FOXP3 but was not significantly changed in culture medium or exosomes, suggesting that circulating miR-155 originated from blood cells. These findings reveal a transcriptional axis of FOXP3-BRCA1-miR-155 in breast cancer cells and show that plasma miR-155 may serve as a non-invasive biomarker for detection of early stage breast cancer.
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