Juan Du

Enhancement of circular RNA 0002577 in serum exosomes in patients with endometrial cancer accelerates disease progression via general transcription factor II-I repeat domain-containing 1 (GTF2IRD1)

Uterine corpus endometrial carcinoma (UCEC) is a common gynecologic malignancy with poor prognosis in advanced stages. Circular RNA (circRNA) and exosomes have been documented as significant contributors to the advancement of tumor cells, but the specific regulatory mechanisms between them is unclear. Therefore, our study attempts to explore the mechanism between them. Firstly, we isolated and identified exosomes, and then validated their role in UCEC progression by experiments in vivo and in vitro. Secondly, a human competing endogenous RNA (ceRNA) array was used to identify the circRNA with the most significant differences in expression from serum of UCEC patient, and validated its role in UCEC progression by experiments in vitro. Then, we find the target gene of this circRNA by RNA sequencing, and further clarify the correlation between those and their role in tumor cell progression through experiments in vitro. Serum exosomes in patients with UCEC can promote the progression of UCEC. The human ceRNA array identified that circRNA 0002577 (circ_0002577) was up-regulated and was the most significantly altered circRNA. Moreover, the up-regulated circ_0002577 in exosomes derived from UCEC patients promote proliferation and migration of UCEC. Based on RNA sequencing results, general transcription factor II-I repeat domain-containing 1 ( Exosomes promote UCEC progression through circ_0002577 mediated regulation of

Polystyrene nanoparticles promote endometrial cancer progression via downregulation of UGT1A genes

The widespread environmental presence of polystyrene nanoparticles (PS-NPs) and their potential health risks have become a growing concern. Concurrently, mortality rates associated with endometrial cancer (EC) have significantly increased in recent years. However, the impact of PS-NPs on the progression of EC remains insufficiently understood. This study investigates the specific biological effects of PS-NPs on EC cell lines and in vivo models. Our findings demonstrate that PS-NPs localize within lysosomes in EC cells and significantly enhance their migratory capacity in vitro. Further in vivo experiments utilizing a Balb/C nude mouse model revealed that exposure to PS-NPs accelerates the growth of EC tumors. Transcriptomic analysis of tumor tissues from PS-NPs-exposed mice showed significant alterations in pathways such as steroid hormone biosynthesis pathways, alongside a widespread downregulation of UGT1A family gene expression. Mechanistically, the targeted knockdown of UGT1A1 and UGT1A10 in EC cells significantly accelerated malignant progression, whereas the overexpression of these genes partially mitigated the malignant phenotype induced by PS-NPs exposure. Collectively, our findings show that PS-NPs promote EC progression by downregulating UGT1A genes (especially UGT1A1 and UGT1A10) and disrupting the homeostasis of the steroid hormone pathway. This research not only introduces a novel perspective for interdisciplinary studies bridging environmental toxicology and gynecological oncology but also provides critical scientific insights into understanding the pathogenesis of EC, developing prevention and treatment strategies, and assessing the safety of NPs.

Exploring the Clinical Signatures of Cervical Dysplasia Patients and Their Association With Vaginal Microbiota

ABSTRACTAimsThe vaginal microbiota plays a crucial role in women's health, and an imbalanced vaginal microbiota is linked to various diseases, including human papillomavirus (HPV) infection. However, most available data comes from Western countries and primarily focuses on HPV infection, with only a few studies considering detailed clinical factors to explore the relationship between vaginal microbiota and the development of cervical cancer, especially in China.Materials and MethodsOur study involved 266 women, including individuals at all stages of cervical dysplasia, and healthy controls with and without HPV infection. We assessed several aspects of the vaginal environment, including vaginal microbiota composition using 16S rRNA gene sequencing, HPV infection status using the standard Roche Cobas method, pH value, age, and H2O2 levels from clinical records, and partner numbers and contraceptive methods obtained through questionnaires. The association of these clinical signatures with cervical dysplasia stages and vaginal microbiota was analyzed.Key FindingsOur findings demonstrate a significant association between vaginal microbiota and cervical dysplasia stages. Patients with cervical dysplasia and cancer showed a substantial increase in HPV 16 infection, a higher prevalence of pH > 5, a lower H2O2 level, and older ages compared to healthy individuals. Additionally, these factors influence the beta diversity of the vaginal microbiota.SignificanceThese results underscore the importance of considering the vaginal microbiota within the cancer microenvironment and highlight the need to integrate all available data to aid in the current diagnosis and understanding of cervical dysplasia and the cervical cancer microenvironment.

Human papilloma virus (HPV) prevalence upon HPV vaccination in Swedish youth: a review based on our findings 2008–2018, and perspectives on cancer prevention

Abstract Purpose Three human papillomavirus (HPV) vaccines are available against up to nine HPV types. In Sweden, from 2012, Gardasil was offered to 10−12 year old girls through the school-based vaccination program, and as catchup vaccination for women up to 26 years. To obtain a baseline, and follow HPV vaccination effects, during 2008−2018, cervical and oral HPV prevalence were followed at a youth clinic in Stockholm, and in 2013 for comparison oral HPV prevalence was examined in high-school youth in a middle-sized county in Sweden. Methods In this review, we discuss all our data with cervical and oral mouthwash samples that were collected and tested for 24−27 HPV types by a bead-based multiplex assay from 2008. Results Compared with 2008−2011, with ~ 35% HPV16 and > 60% high risk (HR) HPV cervical prevalence at the youth clinic, a decrease of vaccine HPV types was observed between 2013 and 2018, with e.g., HPV16 falling to 5% in catchup vaccinated women and 15−18% in nonvaccinated women. Most common cervical HR-HPV types were HPV39, 51, 52, 56, and 59 together accounting for ~ 10% of cervical cancer, and where only HPV52 is included in Gardasil-9. At baseline 2009−2011, oral HPV prevalence was ~ 10% in unvaccinated youth at the youth clinic, but after 2013 it dropped to < 2% at the youth clinic and high schools. Conclusion To conclude, Gardasil HPV types have decreased, but it is still important to follow remaining HR-HPV types and cancer development, since there is an ongoing increase in the incidence of HPV-associated tonsillar and base of tongue cancer, and cervical cancer in Sweden.