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

Abstract

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-κB 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.

Editorial Commentary: Challenge of Non–AIDS-Defining Cancers (NADCs), Focusing on Trans Activation Response Element (TAR) RNA Embedding Exosomes

“…Interestingly, the data from the analysis by Mass Spectrometry showed that, compared to exosomes from uninfected T-cells, exosomes from HIV-1-infected T-cells are enriched in histones, RNA-binding proteins, Cdks and Src family kinases (Barclay et al, 2019). Consistent with the observation in Jin's group on HNSCC and lung cancer, it has been found that exosomes isolated from HIV-1-infected cells promote the growth and progression of cervical cancer as well (Li et al, 2019). In this study, miR-155-5p was identified as the culprit molecule in exosomes to promote the pathogenic progress of HIV-1associated cervical cancer.…”

The versatile role of exosomes in human retroviral infections: from immunopathogenesis to clinical application

“…People living with HIV/AIDS may be at higher risk of cancer, which is known as HIV-associated malignancy (HAM) [100]. Traditionally, HAM is categorized into two types: AIDS-defining cancers (ADCs) and non-AIDS-defining cancers (NADCs).…”

“…Although the underlying mechanism deals with the development and progression of HAM is not yet completely understood, the association between exosomes secreted from HIV-infected cells and HAM has attracted attention in recent years. Li et al investigated that exosomes from HIV-infected T lymphocytes contain miRNA-155-5p which can contribute to the advancement of cervical cancer cells via the ARID2-ERCC5-NF-κB signaling pathway and up-regulating the expression of such cytokines as IL-1, IL-6, and IL-8 [100]. Besides, Chen et al reported that TAR RNA-containing exosomes secreted from HIV-infected T-cells, by activation of the ERK1/2 signaling, may have a potential role in the development of lung cancer and HNSCC [102].…”

ASK1 Enhances Angiotensin II-Induced Liver Fibrosis In Vitro by Mediating Endoplasmic Reticulum Stress-Dependent Exosomes

“…Exosomes were prepared from the cell supernatants of different groups by differential ultracentrifugation as previously described [ 30 ]. In brief, the culture medium was quickly filtered to separate intact cells and debris.…”