HIV-1-infected cell-derived exosomes promote the growth and progression of cervical cancer

HIV-1-infected cell-derived exosomes promote the growth and progression of cervical cancer
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DOI:
10.7150/ijbs.38146
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发表时间:
2019-01-01
影响因子:
9.2
通讯作者:
Chen, Yaokai
Chen, Yaokai
中科院分区:
生物学2区
文献类型:
--
作者:
Li, Haiyu;Chi, Xiangbo;Chen, Yaokai

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背景资料:感染艾滋病毒的妇女更容易患侵袭性宫颈癌,感染艾滋病毒的患者往往比未感染艾滋病毒的患者病情更严重。然而,宫颈癌的进展的潜在机制尚未完全理解,需要进一步的study.Methods:外泌体从细胞培养上清液中分离,使用微分超离心。外泌体分离的确认基于通过电子显微镜和纯化级分的NanoSight颗粒跟踪分析的鉴定。结果:来源于HIV感染T细胞的exosomal miR-155- 5 p促进宫颈癌细胞的增殖、迁移和侵袭,并与对照组相比,差异有统计学意义(P < 0. 05)。此外,我们发现HIV感染的T细胞分泌直接靶向ARID 2降解的外泌体miR-155- 5 p,导致NF-κ B信号通路的激活。miR-155- 5 p通过分泌IL-6和IL-8等促炎细胞因子促进宫颈癌的进展。结论:HIV感染的T细胞与宫颈癌之间的细胞间串扰是由HIV感染的T细胞的exosomes介导的,它促进了宫颈癌的恶性进展,为预防和治疗HIV相关的宫颈癌提供了潜在的靶点。
Background: Women infected with HIV are more likely to have aggressive cervical cancer, and patients with HIV infection are often more severely ill than those without HIV infection. However, the underlying mechanism for the progression of cervical cancer is not yet fully understood and requires further research.Methods: Exosomes were isolated from cell culture supernatants using differential ultracentrifugation. Confirmation of exosome isolation was based upon identification by electron microscopy and NanoSight particle tracking analysis of the purified fraction. The function of exosomes derived from HIV-infected T-cells in cervical cancer was determined by CCK8 and Transwell invasion assays.Results: Exosomal miR-155-5p derived from HIV-infected T-cells promotes the proliferation, migration and invasion of cervical cancer cells. Furthermore, we found that HIV-infected T-cells secrete exosomal miR-155-5p that directly targets ARID2 degradation, leading to activation of the NF-kappa B signaling pathway. MiR-155-5p promotes cervical cancer progression by secreting proinflammatory cytokines, including IL-6 and IL-8.Conclusions: In conclusion, we demonstrate that intercellular crosstalk between HIV-infected T-cells and cervical cancer is mediated by exosomes from HIV-infected T-cells that contribute to the malignant progression of cervical cancer, providing potential targets for the prevention and treatment of HIV-associated cervical cancer.