Project description:Ulcerative colitis is a chronic inflammatory disorder for which a definitive cure is still missing. This is characterized by an overwhelming inflammatory milieu in the colonic tract where a composite set of immune and non-immune cells orchestrate its pathogenesis. Over the last years, a growing body of evidence has been pinpointing gut virome dysbiosis as underlying its progression. Nonetheless, its role during the early phases of chronic inflammation is far from being fully defined. Here we show the gut virome-associated Hepatitis B virus protein X, most likely acquired after an event of zoonotic spillover, to be associated with the early stages of ulcerative colitis and to induce colonic inflammation in mice. It acts as a transcriptional regulator in epithelial cells, provoking barrier leakage and altering mucosal immunity at the level of both innate and adaptive immunity. This study paves the way to the comprehension of the aetiopathogenesis of intestinal inflammation and encourages further investigations of the virome as a trigger also in other scenarios. Moreover, it provides a brand-new standpoint that looks at the virome as a target for tailored treatments, blocking the early phases of chronic inflammation and possibly leading to better disease management.
2023-02-20 | GSE204665 | GEO
Project description:Cervicovaginal virome alterations associated with cervical cancer risk factors
Project description:This study aims to explore the relationship between the respiratory virome, specifically bacteriophages, HERV and the host response in ARDS and to assess their value in predicting the prognosis of ARDS.
Project description:The study examined the infection state of HPV in the Uyghur population with cervical cancer, followed by genotyping to determine the variation in the types of HPV. Using microRNA microarray technology, differential gene expression between HPV-infected cervical cancer and uninfected normal cervical tissues was determined. The microarray results were verified by qRT-PCR using 20 sets of HPV-infected cervical cancer and uninfected cervical tissues.
Project description:Cervical cancer is one of the most common cancers in women worldwide. The role of HPV in cervical cancer is well studied, however, the underlying mechanism promoting cervical tumorigenesis is still not fully understood. Recently, emodin was shown to induce cell cycle arrest, induction of differentiation, downregulation of TGF β signaling pathway and apoptosis in cervical cancer cell lines. Further, recent studies have shown the role of miRNAs in mediating abnormal regulatory mechanisms leading to the pathogenesis of cervical cancer and large scale miRNA profiling studies have examined the use of miRNAs as cervical cancer diagnostic markers. However, to date, there is no study being performed to analyze the changes in miRNAs following emodin treatment to determine whether emodin mediates its effects by regulating the expression of miRNAs. Therefore, the aim of the current study is to perform miRNA profiling in cervical cancer cells following emodin treatment and to analyze the roles of differentially expressed miRNAs in regulating the pathogenesis and treatment of cervical cancer.
Project description:Five human cervical cancer cell lines (HeLa, CaSki, SiHa, C-33A, SW756) and one human normal cervical epithelial cell line HcerEpic were included in the study. Microarray based circRNA expression profiles were acquired using the Arraystar Human circRNA Array (8x15K, Arraystar). We identified circRNAs differentially expressed in human cervical cancer cell lines compared to human normal cervical epithelial HcerEpic cells (control).
Project description:To explore the circRNA expression profiles during the development and progression of cervical cancer, we performed RNA sequencing analysis with ribosomal RNA-depleted in HPV negative normal cervical epithelium, HPV16 positive normal cervical epithelium, HPV16 positive high-grade squamous intraepithelial lesion (HSIL), and HPV16 positive cervical squamous cell carcinoma tissues,6 cases in each group.Totally 66868 circRNAs were identified (Back-spliced junctions reads≥1)
Project description:Cervical cancer results from the accumulation of (epi)genetic aberrations following persistent infection with high-risk human papillomavirus (HPV). In order to define genetic aberrations associated with cervical carcinogenesis, chromosomal profiles of high-grade cervical intraepithelial neoplasia (CIN) were generated. Common aberrations usually encompass large genomic regions and contain numerous genes, hampering identification of actual driver genes. Consequently, direct evidence of chromosomal alterations actively contributing to cervical carcinogenesis has been lacking so far. By analyzing 60 high-grade CIN with high resolution arrayCGH we identified focal chromosomal aberrations that each harbour only one or a few genes. In total 74 focal aberrations were identified encoding 305 genes. Analysis of genes located within these focal aberrations, using two independent expression microarray datasets, revealed concurrent altered expression in high-grade CIN and/or cervical carcinomas compared to normal cervical samples for 8 genes: ATP13A3, HES1, OPA1, HRASLS, EYA2, ZMYND8, APOBEC2 and NCR2. Gene silencing of EYA2, located within a focal gain at 20q13, significantly reduced viability and migratory capacity of HPV16-transformed keratinocytes. Interestingly, for hsa-miR-375, located within the most frequently identified focal loss at 2q35, a direct correlation between a (focal) loss and significantly reduced expression was found. Down-regulation of hsa-miR-375 expression during cervical carcinogenesis was confirmed in a second independent series of cervical tissues. Moreover, ectopic expression of hsa-miR-375 in 2 cervical carcinoma cell lines reduced cellular viability. In conclusion, our data provide a proof of concept that chromosomal aberrations are actively contributing to HPV-induced carcinogenesis and identify EYA2 and hsa-mir-375 as oncogene and tumor suppressor gene, respectively. DNA from microdissected tissues: 60 samples total. 11 high-grade CIN, <5yr preceding hrHPV infection, 43 high-grade CIN >5yr preceding hrHPV infection, 6 CIN3 adjacent to SCC