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Abstract：
BACKGROUND: Cervical cancer is a common malignant tumor in the female. Interleukin (IL)-17A is a proinflammatory factor and exerts a vital function in inflammatory diseases and cancers. M2 macrophage has been confirmed to promote tumor development. Nevertheless, it is not yet known whether IL-17A facilitates cervical cancer development by inducing M2 macrophage polarization. Therefore, this study was conducted to investigate the regulatory effect of IL-17A on M2 macrophage polarization and the underlying mechanism in cervical cancer development.
METHODS: RT-qPCR was utilized for testing IL-17A expression in cancer tissues and cells. Flow cytometry was applied to evaluate the M1 or M2 macrophage polarization. Cell proliferative, migratory, and invasive capabilities were measured through colony formation and transwell assays. ChIP and luciferase reporter assays were applied to determine the interaction between IL-17A and octamer-binding transcription factor 4 (OCT4).
RESULTS: IL-17A expression and concentration were high in metastatic tissues and cells of cervical cancer. IL-17A was found to facilitate M2 macrophage polarization in cervical cancer. Furthermore, IL-17A facilitated the macrophage-mediated promotion of cervical cancer cell proliferative, migratory, and invasive capabilities. Mechanistic assays manifested that Oct4 binds to and transcriptionally activated IL-17A in cervical cancer cells. Furthermore, Oct4 promoted cervical cancer cell malignant phenotype and M2 macrophage polarization by activating the p38 pathway that, in turn, upregulated IL-17A. Additionally, in vivo experiments confirmed that Oct4 knockdown reduced tumor growth and metastasis.
CONCLUSIONS: Oct4 triggers IL-17A to facilitate the polarization of M2 macrophages, which promotes cervical cancer cell metastasis.
METHODS: RT-qPCR was utilized for testing IL-17A expression in cancer tissues and cells. Flow cytometry was applied to evaluate the M1 or M2 macrophage polarization. Cell proliferative, migratory, and invasive capabilities were measured through colony formation and transwell assays. ChIP and luciferase reporter assays were applied to determine the interaction between IL-17A and octamer-binding transcription factor 4 (OCT4).
RESULTS: IL-17A expression and concentration were high in metastatic tissues and cells of cervical cancer. IL-17A was found to facilitate M2 macrophage polarization in cervical cancer. Furthermore, IL-17A facilitated the macrophage-mediated promotion of cervical cancer cell proliferative, migratory, and invasive capabilities. Mechanistic assays manifested that Oct4 binds to and transcriptionally activated IL-17A in cervical cancer cells. Furthermore, Oct4 promoted cervical cancer cell malignant phenotype and M2 macrophage polarization by activating the p38 pathway that, in turn, upregulated IL-17A. Additionally, in vivo experiments confirmed that Oct4 knockdown reduced tumor growth and metastasis.
CONCLUSIONS: Oct4 triggers IL-17A to facilitate the polarization of M2 macrophages, which promotes cervical cancer cell metastasis.
摘要：
背景：宫颈癌是女性常见的恶性肿瘤。白细胞介素（IL）-17A是一种促炎因子，在炎症性疾病和癌症中发挥重要作用。M2巨噬细胞已被证实增进肿瘤发展。然而，目前尚不清楚IL-17A是否通过诱导M2巨噬细胞极化促进宫颈癌的发展.因此,本研究旨在探讨IL-17A对M2巨噬细胞极化的调节作用及其在宫颈癌发生发展中的作用机制。
方法：RT-qPCR用于检测IL-17A在癌组织和细胞中的表达。流式细胞术用于评估M1或M2巨噬细胞极化。细胞增殖性,迁徙,和侵入能力通过集落形成和transwell测定来测量。应用ChIP和荧光素酶报告基因测定来确定IL-17A与八聚体结合转录因子4(OCT4)之间的相互作用。
结果：IL-17A在宫颈癌转移组织和细胞中的表达和浓度均较高。发现IL-17A促进宫颈癌中的M2巨噬细胞极化。此外，IL-17A促进巨噬细胞介导的宫颈癌细胞增殖,迁徙,和侵入能力。机制测定表明0ct4结合并转录激活宫颈癌细胞中的IL-17A。此外，Oct4通过激活p38通路促进宫颈癌细胞恶性表型和M2巨噬细胞极化,反过来,上调IL-17A。此外,体内实验证实Oct4敲低降低了肿瘤的生长和转移。
结论：Oct4触发IL-17A促进M2巨噬细胞的极化，促进宫颈癌细胞转移。
方法：RT-qPCR用于检测IL-17A在癌组织和细胞中的表达。流式细胞术用于评估M1或M2巨噬细胞极化。细胞增殖性,迁徙,和侵入能力通过集落形成和transwell测定来测量。应用ChIP和荧光素酶报告基因测定来确定IL-17A与八聚体结合转录因子4(OCT4)之间的相互作用。
结果：IL-17A在宫颈癌转移组织和细胞中的表达和浓度均较高。发现IL-17A促进宫颈癌中的M2巨噬细胞极化。此外，IL-17A促进巨噬细胞介导的宫颈癌细胞增殖,迁徙,和侵入能力。机制测定表明0ct4结合并转录激活宫颈癌细胞中的IL-17A。此外，Oct4通过激活p38通路促进宫颈癌细胞恶性表型和M2巨噬细胞极化,反过来,上调IL-17A。此外,体内实验证实Oct4敲低降低了肿瘤的生长和转移。
结论：Oct4触发IL-17A促进M2巨噬细胞的极化，促进宫颈癌细胞转移。
