Dataset Information

Dysregulation of an X-linked primate-specific epididymal microRNA cluster in unexplained asthenozoospermia.

ABSTRACT: Asthenoszoopermia, characterized by reduced sperm motility, is one of the primary forms of male infertility. Whereas most cases were diagnosed into unexplained asthenozoospermia (UA) because the etiology cannot be identified. In animal models, epigenetic dysregulation in epididymis can impair sperm maturation and result in asthenozoospermia. However, researches of epididymal epigenetic regulation on humans are impeded by the difficulty in obtaining epididymal tissues. We previously identified cell-free seminal microRNAs predominately derived from epididymis in human ejaculate. In the present study, these microRNAs were used to screen and validate the microRNA dysregulation in men with UA, which were divided into screening set and validation set. The expression of five miRNAs (miR-891b, miR-892b, miR-892a, miR-888 and miR-890) was found and confirmed to be dysregulated in men with UA. Interestingly, these five miRNAs belong to a primate-specific miRNA cluster located on the X chromosome with epididymis specific expression. Moreover, obvious coherent dysregulation of these miRNAs were observed in 13% men with UA. Regression analysis demonstrated that levels of these miRNAs were significantly correlated with progressive sperm motility. Functions and pathways of predicted target genes of this cluster suggested its role in sperm maturation. Dysregulation of this miRNA cluster might be an epigenetic basis for some patients with UA. We also showed a noninvasive and feasible approach to get epigenetic information of human epididymis.

SUBMITTER: Qing X

PROVIDER: S-EPMC5593606 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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Dysregulation of an X-linked primate-specific epididymal microRNA cluster in unexplained asthenozoospermia.

Qing Xingrong X Shi Jian J Dong Tingting T Wu Chunlin C Hu Lian L Li Honggang H

Oncotarget 20170523 34

Asthenoszoopermia, characterized by reduced sperm motility, is one of the primary forms of male infertility. Whereas most cases were diagnosed into unexplained asthenozoospermia (UA) because the etiology cannot be identified. In animal models, epigenetic dysregulation in epididymis can impair sperm maturation and result in asthenozoospermia. However, researches of epididymal epigenetic regulation on humans are impeded by the difficulty in obtaining epididymal tissues. We previously identified ce ...[more]

PMID: 28915635

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Project description:BACKGROUND:Current evidence implicates aberrant microRNA expression patterns in human malignancies; measurement of microRNA expression may have diagnostic and prognostic applications. Roles for microRNAs in head and neck squamous cell carcinomas (HNSCC) are largely unknown. HNSCC, a smoking-related cancer, is one of the most common malignancies worldwide but reliable diagnostic and prognostic markers have not been discovered so far. Some studies have evaluated the potential use of microRNA as biomarkers with clinical application in HNSCC. METHODS:MicroRNA expression profile of oral squamous cell carcinoma samples was determined by means of DNA microarrays. We also performed gain-of-function assays for two differentially expressed microRNA using two squamous cell carcinoma cell lines and normal oral keratinocytes. The effect of the over-expression of these molecules was evaluated by means of global gene expression profiling and cell proliferation assessment. RESULTS:Altered microRNA expression was detected for a total of 72 microRNAs. Among these we found well studied molecules, such as the miR-17-92 cluster, comprising potent oncogenic microRNA, and miR-34, recently found to interact with p53. HOX-cluster embedded miR-196a/b and miR-10b were up- and down-regulated, respectively, in tumor samples. Since validated HOX gene targets for these microRNAs are not consistently deregulated in HNSCC, we performed gain-of-function experiments, in an attempt to outline their possible role. Our results suggest that both molecules interfere in cell proliferation through distinct processes, possibly targeting a small set of genes involved in cell cycle progression. CONCLUSIONS:Functional data on miRNAs in HNSCC is still scarce. Our data corroborate current literature and brings new insights into the role of microRNAs in HNSCC. We also show that miR-196a and miR-10b, not previously associated with HNSCC, may play an oncogenic role in this disease through the deregulation of cell proliferation. The study of microRNA alterations in HNSCC is an essential step to the mechanistic understanding of tumor formation and could lead to the discovery of clinically relevant biomarkers.

Dataset Information

Dysregulation of an X-linked primate-specific epididymal microRNA cluster in unexplained asthenozoospermia.

Publications

Dysregulation of an X-linked primate-specific epididymal microRNA cluster in unexplained asthenozoospermia.

Similar Datasets

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