Department of Infectious Diseases, Chongqing Public Health Medical Center, Chongqing, China.
Departments of Department of Gastroenterology, Chongqing Public Health Medical Center, Southwest University, Chongqing, China.
Int J Biol Sci. 2019 Sep 7;15(11):2438-2447. doi: 10.7150/ijbs.38146. eCollection 2019.
: 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. : 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. : 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-κB signaling pathway. MiR-155-5p promotes cervical cancer progression by secreting proinflammatory cytokines, including IL-6 and IL-8. : 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.
: 感染 HIV 的女性更容易患上侵袭性宫颈癌,并且感染 HIV 的患者通常比未感染 HIV 的患者病情更为严重。然而,宫颈癌进展的潜在机制尚未完全阐明,需要进一步研究。 : 使用差速超速离心法从细胞培养上清液中分离出外泌体。通过电子显微镜和纳米粒子跟踪分析对纯化部分进行鉴定,确认了外泌体的分离。通过 CCK8 和 Transwell 侵袭实验确定了源自 HIV 感染 T 细胞的外泌体在宫颈癌中的功能。 : HIV 感染 T 细胞衍生的外泌体 miR-155-5p 促进宫颈癌细胞的增殖、迁移和侵袭。此外,我们发现 HIV 感染的 T 细胞分泌外泌体 miR-155-5p,可直接靶向 ARID2 降解,从而激活 NF-κB 信号通路。miR-155-5p 通过分泌促炎细胞因子,包括 IL-6 和 IL-8,促进宫颈癌的进展。 : 总之,我们证明了 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 细胞来源的外泌体介导的,这有助于宫颈癌的恶性进展,为预防和治疗与 HIV 相关的宫颈癌提供了潜在的靶点。