PDF(Pubmed)
Abstract：
miRNA155 (miR155) has emerged as an important regulator of breast cancer (BrCa) development. Studies have consistently noted an increase in miR155 levels in serum and/or tissues in patients with BrCa. However, what is less clear is whether this increase in miR155 is a reflection of oncogenic or tumor suppressive properties. To study the effects of miR155 in a transgenic model of BrCA, we developed an MMTV-PyMT mouse deficient in miR155 (miR155-/- PyMT). miR155-/- mice (n = 11) exhibited reduced tumor number and volume palpations at ∼14-18 wk of age compared with miR155 sufficient littermates (n = 12). At 19 wk, mammary glands were excised from tumors for RT-PCR, and tumors were counted, measured, and weighed. miR155-/- PyMT mice exhibited reduced tumor volume, number, and weight, which was confirmed by histopathological analysis. There was an increase in apoptosis with miR155 deficiency and a decrease in proliferation. As expected, miR155 deficiency resulted in upregulated gene expression of suppressor of cytokine signaling 1 (Socs1)-its direct target. There was a reduction in gene expression of macrophage markers (CD68, Adgre1, Itgax, Mrc1) with miR-155-/- and this was confirmed with immunofluorescence staining for F4/80. miR155-/- increased expression of M1 macrophage marker Nos2 and reduced expression of M2 macrophage markers IL-10, IL-4, Arg1, and MMP9. Overall, miR155 deficiency reduced BrCA and improved the tumor microenvironment through the reduction of genes associated with protumorigenic processes. However, given the inconsistencies in the literature, additional studies are needed before any attempts are made to harness miR155 as a potential oncogenic or tumor suppressive miRNA.NEW & NOTEWORTHY To examine the effects of miR155 in a transgenic model of breast cancer, we developed an MMTV-PyMT mouse-deficient in miR155. We demonstrate that global loss of miR155 resulted in blunted tumor growth through modulating the tumor microenvironment. Specifically, miR155-deficient mice had smaller and less invasive tumors, an increase in apoptosis and a decrease in proliferation, a reduction in tumor-associated macrophages, and the expression of genes associated with protumoral processes.
摘要：
miR155已成为乳腺癌（BrCa）发展的重要调节剂。研究一致注意到BrCa患者血清和/或组织中miR155水平的增加。然而,尚不清楚的是miR155的这种增加是否是致癌或肿瘤抑制特性的反映。为了研究miR155在BrCA转基因模型中的作用，我们开发了缺乏miR155(miR155-/-PyMT)的MMTV-PyMT小鼠。与miR155足够的同窝动物(n=12)相比,miR155-/-小鼠(n=11)在约14-18周龄时表现出减少的肿瘤数量和体积触诊。在19周，从肿瘤中切除乳腺进行RT-PCR，肿瘤被计数，测量，称重。miR155-/-PyMT小鼠表现出肿瘤体积减小，number,和体重,组织病理学分析证实了这一点。miR155缺陷导致细胞凋亡增加，增殖减少。不出所料,miR155缺陷导致细胞因子信号传导抑制因子1(Socs1)的基因表达上调-其直接靶标。巨噬细胞标记的基因表达减少(CD68，Adgre1，Itgax，Mrc1）与miR-155-/-，这通过F4/80的免疫荧光染色得到证实。miR155-/-增加M1巨噬细胞标记物Nos2的表达，并减少M2巨噬细胞标记物IL-10，IL-4，Arg1和MMP9的表达。总的来说,miR155缺乏通过减少与促肿瘤发生过程相关的基因来减少BrCA并改善肿瘤微环境。然而,鉴于文献中的不一致之处，在尝试利用miR155作为潜在的致癌或肿瘤抑制性miRNA之前,还需要进一步的研究.
