LncRNA-MALAT1 Promotes Angiogenesis of Thyroid Cancer by Modulating Tumor-Associated Macrophage FGF2 Protein Secretion
LncRNA-MALAT1 Promotes Angiogenesis of Thyroid Cancer by Modulating Tumor-Associated Macrophage FGF2 Protein Secretion
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DOI：
10.1002/jcb.26153
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发表时间：
2017-12-01
影响因子：
4
通讯作者：
Zhou, Rui
中科院分区：
文献类型：
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作者：
Huang, Jian-kang;Ma, Ling;Zhou, Rui
肿瘤微环境中的肿瘤相关巨噬细胞（TAM）与肿瘤进展加速有关。在这项研究中，我们研究了 MALAT1 在甲状腺癌 TAM 中的作用和分子机制。采用实时荧光定量PCR和Western blot检测甲状腺癌组织和细胞中MALAT1和FGF2的表达。 TAM 用指定的构建体转染。然后收获 TAM 的培养基 (CM) 用于分析。通过ELISA检测分泌的FGF2蛋白水平以及TNF-、IL-12和IL-10水平。分别用CCK-8法和Transwell法测定FTC133细胞的细胞增殖、迁移和侵袭。此外，通过基质胶血管生成测定来测量HUVEC脉管系统形成。与对照组相比，甲状腺癌组织和甲状腺癌细胞中 MALAT-1 和 FGF2 的水平较高。此外，在 si-MALAT1 存在的情况下，TAM 的 CM 中 TNF- 和 IL-12 的水平显着上调，而 IL-10 的水平下调。此外，TAM 中 MALAT1 的下调会减少 FTC133 细胞的增殖、迁移和侵袭，并抑制血管生成。然而，FGF2 的过度表达阻断了 MALAT1 siRNA 对细胞迁移、侵袭和血管生成的影响。我们的结果表明，MALAT1 介导的 TAM 分泌的 FGF2 蛋白抑制炎症细胞因子的释放，促进 FTC133 细胞的增殖、迁移和侵袭，并诱导脉管系统形成。 J.细胞。生物化学。 118：4821-4830，2017 年。(c) 2017 年 Wiley 期刊公司。
Tumor-associated macrophages (TAMs) in the tumor microenvironment have been associated with enhanced tumor progression. In this study, we investigated the role and molecular mechanisms of MALAT1 in TAMs derived from thyroid cancer. The expression of MALAT1 and FGF2 in thyroid cancer tissues and cells were measured by quantitative real-time PCR and Western blot. TAMs were transfected with indicated constructs. Then the culture medium (CM) from TAMs was harvested for assay. Secreted FGF2 protein levels and TNF-, IL-12, and IL-10 levels were detected by ELISA. The cell proliferation, migration, and invasion of FTC133 cells were determined with a CCK-8 assay and a Transwell assay, respectively. In addition, HUVEC vasculature formation was measured by matrigel angiogenesis assay. The higher levels of MALAT-1 and FGF2 were observed in thyroid cancer tissues and in thyroid cancer cells compared to that in the control. Besides, in the presence of si-MALAT1, the levels of TNF- and IL-12 were significantly up-regulated whereas IL-10 was down-regulated in the CM from TAMs. Moreover, down-regulation of MALAT1 in TAMs reduced proliferation, migration, and invasion of FTC133 cells and inhibited angiogenesis. However, overexpression of FGF2 blocked the effects of MALAT1 siRNAs on cell migration, invasion, and angiogenesis. Our results suggest that MALAT1-mediated FGF2 protein secretion from TAMs inhibits inflammatory cytokines release, promotes proliferation, migration, and invasion of FTC133 cells and induces vasculature formation. J. Cell. Biochem. 118: 4821-4830, 2017. (c) 2017 Wiley Periodicals, Inc.