Because altered microRNAs (miRNAs) expression patterns have been observed in a variety of diseased tissues, miRNA expression was compared in human cervical cancer tissues relative to adjacent normal cervical tissues in the present study. Microarray chips with 924 probes were used to detect the expression of miRNAs in cervical cancer tissue and adjacent normal cervical tissue of 13 patients with cervical cancer (11 squamous cervical cancers, one cervical adenocarcinoma, and one cervical sarcoma), all of whom were infected with human papilloma virus (HPV) 16 and/or HPV18. Compared to the expression levels in normal cervical tissues, 18 miRNAs (1.9%) were significantly upregulated (increase of ≥2×), and 19 miRNAs (2.1%) were significantly downregulated (decrease of ≤0.5×) in cervical cancer tissues. miRNA expression was independent of lymph node involvement, vascular invasion, and pathological differentiation. Taken together, cervical cancer tissues have altered expression of miRNAs relative to adjacent normal tissues. Further studies are necessary to determine whether aberrant miRNA expression is related to the pathogenesis of cervical cancer.
[Show abstract][Hide abstract] ABSTRACT: Background: miRNAs are a class of small non-coding RNAs that are approximately 21-24 nucleotides in length and regulate gene expression post-transcriptionally by way of translational repression or transcript cleavage. They are undoubtedly dysregulated in several neoplastic events but the discordant reports trailing some of them have limited their application in diagnostic pathology. The aim of this review was to evaluate reports of miRNA dysregulation in cervical cancer in a bid to finding explanation for the discordance and to identify the best diagnostic and prognostic biomarker for cervical cancer. Method: Articles on miRNA expression in cervical cancer were downloaded from journal websites, Google scholar, Pubmed and Researchgate. The MiRNAs were classified using two criteria; 1) Frequency of reports using a scale of: 6-5 for Class I, 4-3 for Class II, 2 for Class III and 1 report for Class IV; 2) status of controversy, which included: Controversial (C) and Uncontroversial (UC). The controversial group was subdivided into Most Controversial (MC; >25%) and Less Controversial (LC; ≤25%). Result: Sixty-six (66) miRNAs were found to be dysregulated in cervical cancers, out of which 9 (13.6%) miRNAs were controversial, 20 (30.3%) miRNAs were uncontroversial and 37 (56.1%) miRNAs are yet to be validated by other reports. Considering frequency of reports, 5 miRNAs (7.7%), 13 miRNAs (20%), 10 miRNAs (15.4%) and 37 (56.9%) were grouped into Class I, II, III and IV, respectively. In all, only 8 (12%) miRNAs (miR-21, miR-18a, miR-20a, miR-29a, miR-25, miR-183, miR-196a, miR-218) were found to be most reported and without controversy. Conclusions: the expression of miRNAs is affected by overlapping factors such as cancer stage, type of sample analyzed, technique employed, type of viral agent and oncoprotein present. In is important that this factors be considered prior to sample analysis. Since miR-21 is more frequently reported without any discordance when compared with other miRNAs, it should be adopted as the best biomarker in monitoring and management of cervical cancer patients.
"The expressions of the 2 novel miRNAs were not correlated with tumor stage, lymph node metastasis or pathological differentiation (all P > 0.05), which indicates that, although the aberrant expression of the 2 miRNAs may be unrelated to the advancement of cancer, the expression of these miRNAs may be related to the occurrence of cervical cancer. These results were consistent with a study by Qunxian Rao et al., which found miRNA expression was independent of lymph node involvement, vascular invasion, and pathological differentiation18. Analysis of an miRNA-gene-network revealed that IL-1β, MAP3K14, PAX 7, PIGK, SEMA5B and TSHR were key target genes for the 2 novel miRNAs. "
[Show abstract][Hide abstract] ABSTRACT: Small non-coding microRNAs (miRNAs) are involved in cancer development and progression, and serum profiles of cervical cancer patients may be useful for identifying novel miRNAs. We performed deep sequencing on serum pools of cervical cancer patients and healthy controls with 3 replicates and constructed a small RNA library. We used MIREAP to predict novel miRNAs and identified 2 putative novel miRNAs between serum pools of cervical cancer patients and healthy controls after filtering out pseudo-pre-miRNAs using Triplet-SVM analysis. The 2 putative novel miRNAs were validated by real time PCR and were significantly decreased in cervical cancer patients compared with healthy controls. One novel miRNA had an area under curve (AUC) of 0.921 (95% CI: 0.883, 0.959) with a sensitivity of 85.7% and a specificity of 88.2% when discriminating between cervical cancer patients and healthy controls. Our results suggest that characterizing serum profiles of cervical cancers by Solexa sequencing may be a good method for identifying novel miRNAs and that the validated novel miRNAs described here may be cervical cancer-associated biomarkers.
"Changes in the expression profile of miRNAs have been reported in cervical cancer cell lines, cervical cancer tissue and precursor lesions (1,11–13). Similarly, studies conducted in cell lines suggest that HPV participates in deregulating miRNA expression by modifying the expression profile of miRNAs associated with the presence of HPV and the viral genotype (1,5,11,14,15). Given that a considerable number of miRNAs are subject to epigenetic regulation, it has been proposed that aberrant methylation of miRNA promoters is one of the mechanisms responsible for deregulated miRNA expression in cervical cancer (2,12,16). "
[Show abstract][Hide abstract] ABSTRACT: Cancer is a complex disease caused by genetic and epigenetic abnormalities that affect gene expression. The progression from precursor lesions to invasive cervical cancer is influenced by persistent human papilloma virus (HPV) infection, which induces changes in the host genome and epigenome. Epigenetic alterations, such as aberrant miRNA expression and changes in DNA methylation status, favor the expression of oncogenes and the silencing of tumor-suppressor genes. Given that some miRNA genes can be regulated through epigenetic mechanisms, it has been proposed that alterations in the methylation status of miRNA promoters could be the driving mechanism behind their aberrant expression in cervical cancer. For these reasons, we assessed the relationship among HPV infection, cellular DNA methylation and miRNA expression. We conclude that alterations in the methylation status of protein-coding genes and various miRNA genes are influenced by HPV infection, the viral genotype, the physical state of the viral DNA, and viral oncogenic risk. Furthermore, HPV induces deregulation of miRNA expression, particularly at loci near fragile sites. This deregulation occurs through the E6 and E7 proteins, which target miRNA transcription factors such as p53.
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