Changes of miRNA Expression Profiles from Cervical-Vaginal Fluid-Derived Exosomes in Response to HPV16 Infection

As an oncogenic virus, HPV16 can lead to the dysfunction of cervical epithelial cells and contribute to the progression of cervical cancer. Components from the cervical-vaginal fluid (CVF) could be used as the basis for cervical cancer screening. Exosomes are widely present in various body fluids and participate in intercellular communication via its cargos of proteins, mRNAs, and miRNAs. This study was conducted to explore the changes of miRNAs in exosomes isolated form the cervical-vaginal fluid during HPV16 infection and to predict the potential effects of exosomal miRNAs on the development of cervical cancer. CVF was collected from volunteers with or without HPV16 infection. The exosomes in CVF were identified by electron microscopy. Microarray analysis was subjected to find the differentially expressed miRNAs in CVF exosomes. To confirm the results, 16 miRNAs were randomly selected to go through real-time quantitative polymerase chain reaction. In addition, GO and pathway analyses were conducted to reveal potential functions of differentially expressed miRNAs. A total of 2548 conserved miRNAs were identified in the cervical-vaginal fluid-derived exosomes. In response to HPV16 infection, 45 miRNAs are significantly upregulated and 55 miRNAs are significantly downregulated (P < 0.05). The GO and KEGG pathway analyses revealed that these differentially expressed miRNAs are tightly associated with cervical cancer tumorigenesis, through interaction with the Notch signaling pathway, TNF signaling pathway, and TGF-β signaling pathway. These results suggest that exosomal miRNAs in CVF are differentially expressed in HPV16 infection patients and HPV16-free volunteers. It provided a novel insight to understand the underlying mechanism of HPV16 infection in regulating cervical cancer progression.