Functions of miR-146a and miR-222 in Tumor-associated Macrophages in Breast Cancer.
Functions of miR-146a and miR-222 in Tumor-associated Macrophages in Breast Cancer.
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DOI：
10.1038/srep18648
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发表时间：
2015-12-22
影响因子：
4.6
通讯作者：
Shi J
中科院分区：
文献类型：
--
作者：
Li Y;Zhao L;Shi B;Ma S;Xu Z;Ge Y;Liu Y;Zheng D;Shi J
肿瘤相关巨噬细胞（TAMs）在促进肿瘤进展和侵袭中起着关键作用。然而，TAM调控的分子机制仍有待进一步研究，并可能对癌症治疗做出重大贡献。哺乳动物microRNAs （miRNAs）最近被确定为基因表达的重要调控因子，主要在转录后水平上抑制特定靶基因。然而，对肿瘤组织中TAMs中mirna的功能和机制的系统研究尚不多见。在这项研究中，miR-146a和miR-222在与NF-κB p50亚基上调相关的tam中显著降低。miR-146a促进了部分M2巨噬细胞表型分子的表达，miR-146a antagomir转染RAW264.7单核巨噬细胞在体内抑制4T1肿瘤的生长。同时，过表达miR-222抑制TAM趋化，TAM中的miR-222通过靶向CXCL12抑制CXCR4抑制4T1肿瘤生长。这些数据表明，mirna通过促进M2型极化或调节tam的募集来影响乳腺肿瘤的生长。这些观察结果表明，内源性miRNAs可能在乳腺癌中调控tam的极化和功能方面发挥重要作用。
Tumor-associated macrophages (TAMs) play critical roles in promoting tumor progression and invasion. However, the molecular mechanisms underlying TAM regulation remain to be further investigated and may make significant contributions to cancer treatment. Mammalian microRNAs (miRNAs) have recently been identified as important regulators of gene expression that function by repressing specific target genes mainly at the post-transcriptional level. However, systematic studies of the functions and mechanisms of miRNAs in TAMs in tumor tissues are rare. In this study, miR-146a and miR-222 were shown to be significantly decreased in TAMs associated with the up-regulated NF-κB p50 subunit. miR-146a promoted the expression of some M2 macrophage phenotype molecules, and miR-146a antagomir transfected RAW264.7 monocyte-macrophage cells inhibited 4T1 tumor growth in vivo. Meanwhile, overexpression of miR-222 inhibited TAM chemotaxis, and miR-222 in TAMs inhibited 4T1 tumor growth by targeting CXCL12 and inhibiting CXCR4. These data revealed that miRNAs influence breast tumor growth by promoting the M2 type polarization or regulating the recruitment of TAMs. These observations suggest that endogenous miRNAs may exert an important role in controlling the polarization and function of TAMs in breast cancer.