Project description:Background. MicroRNAs (miRNAs) are short (~22 nt) non-coding regulatory RNAs that control gene expression at the translational level. Deregulation of miRNA expression has been discovered in a wide variety of tumours and it is now clear that they contribute to cancer development and progression. This prompted the development of miRNA-chips for cancer diagnosis or prognosis, opening a new door to understand carcinogenesis. Cervical cancer is one of the most common cancers in women worldwide. Therefore, there is a strong need for a non-invasive, fast and efficient method to diagnose the disease. We investigated miRNA expression profiles in cervical cancer using a microarray platform developed in house containing probes for mature miRNAs. Results. We have evaluated miRNA expression profiles of a heterogeneous set of cervical tissues from 25 different patients. This set included 19 normal cervical tissues, 4 squamous cell carcinoma, 5 high-grade squamous intraepithelial lesion (HSIL) and 9 low-grade squamous intraepithelial lesion (LSIL) samples. We observed high variability in miRNA expression especially among normal cervical samples, which prevented us from obtaining a unique miRNA expression signature for this tumour type. However, miRNAs deregulation in malignant and pre-malignant cervical tissues was detected after tackling the high variability observed. We were also able to identify putative targets of relevant candidate miRNAs. Conclusions. Our results show that miRNA deregulation may play an important role in the malignant transformation of cervical squamous cells. In addition, deregulated miRNAs highlight new candidate targets allowing a better understanding of the molecular mechanism of this tumour type.
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 intraepithelial neoplasia (CIN), also known as cervical dysplasia, is premalignant lesions of the cervical squamous cell carcinoma (CSCC) that shows abnormal growth of squamous cells in the cervix epithelium. Given the evidence suggesting that differences may exist between CIN and CSCC, we hypothesize that progression may be mediated by subpopulation selection or by acquisition of additional alterations, including gene mutations or chromosomal alterations. In this study, we analyzed cervical CIN, microinvasive carcinoma (MIC) and CSCC by whole-exome sequencing and array-comparative genomic hybridization (array-CGH) and found that CIN genomes harbored fewer mutations (especially fewer driver mutations) and copy number alterations (CNAs), suggesting that additional genomic alterations might burst onto the CIN genome at the final stage of CIN progression to CSCC or an early stage of CSCC.
Project description:Cervical mucus was collected from 86 patients with a normal cervix, cervical intraepithelial neoplasia (CIN), squamous cell carcinoma (SCC), or adenocarcinoma (AD). 76 candidates of miRNAs were selected according to criteria such as absolute value of the signal intensity included more than 20 and the ratio of the SCC/normal or AD/normal included more than four.
Project description:<p>Introduction: Cervical cancer is the fourth most common malignancy in women and is primarily caused by persistent infection with high-risk human papillomavirus (HPV). In addition, host immune responses, genetic factors, and lifestyle habits also have etiological roles. The cervicovaginal microbiome undergoes dynamic changes during menopause, which may be involved in the progression of cervical neoplasia. We aimed to elucidate the association between cervical microenvironmental changes and the progression of cervical neoplasia before and after menopause by integrating analyses of the cervical microbiome, related metabolites, cytokines, and microRNAs. Methods: A total of 248 HPV-positive women with cervical neoplasia, including 17 with cervical intraepithelial neoplasia (CIN1), 80 with CIN2, 82 with CIN3, and 69 with squamous cell carcinoma (SCC), were enrolled. As normal controls, 48 HPV-negative healthy women were included. Each group was stratified based on the mean menopausal age of 50 years. Cervical mucus was analyzed according to the methods outlined below. The microbiota was profiled by 16S rRNA gene sequencing, metabolites were analyzed by ultra-HPLC-tandem mass spectrometry, RT-qPCR was used for miRNA expression analysis, and RANTES levels were quantified by multiplex bead array. Data analysis was performed using MicrobiomeAnalyst and MetaboAnalyst.Results: In the SCC group, Prevotella and Atopobium were the key bacterial genera among the younger group, while Peptoniphilus, Fusobacterium, and Porphyromonas were more prevalent in elderly group (LDA score > 4.5). We observed a consistent positive correlation between Atopobium and xanthine in younger groups with CIN2 or worse (p < 0.0001). However, no such correlations were detected in elderly women. In addition, Atopobium, Adlercreutzia, and Gardnerella showed significant positive correlation with nicotinic acid in younger women with SCC compared to the elderly women (p < 0.0001). In the younger SCC women, several metabolites were significantly elevated in groups with high expression levels of RANTES, miR-20b-5p, and miR-155-5p.The cervical microbiome undergoes changes during menopause, and may influence disease progression by interacting with metabolites, cytokines, and miRNAs. These results highlight the potential for personalized medicine for cervical cancer that is tailored to different age groups.Please update the study abstract/description</p>
Project description:Cervical cancer is characterized by a well-defined pre-malignant phase, cervical intraepithelial neoplasia (CIN). Identification of high grade CIN lesions by population-based screening programs and their subsequent treatment has led to a significant reduction of the incidence and mortality of cervical cancer. Cytology-based testing of cervical smears is the most widely used cervical cancer screening method, but is not ideal, as the sensitivity for detection of CIN2 and higher (CIN2+) is only ~55%. Therefore, more sensitive and specific biomarkers for cervical cancer and its precancerous stages are needed.
Project description:To investigate the differences in mRNA profiles specially related to metabolism in cervical cancer, 5 primary cervical cancer tissues and 6 normal cervical tissues were collected. The differential expression of metabolism-associated-mRNA was verified using qRT-PCR.