1,720,980 research outputs found
Dietary phytochemicals for possible preventive and therapeutic option of uterine fibroids: Signaling pathways as target
No full textA Practical Guide to miRNA Target Prediction
No full textMicroRNAs (miRNAs) are small endogenous noncoding RNA molecules that posttranscriptionally regulate gene expression. Since their discovery, a huge number of miRNAs have been identified in a wide range of species. Through binding to the 3' UTR of mRNA, miRNA can block translation or stimulate degradation of the targeted mRNA, thus affecting nearly all biological processes. Prediction and identification of miRNA target genes is crucial toward understanding the biology of miRNAs. Currently, a number of sophisticated bioinformatics approaches are available to perform effective prediction of miRNA target sites. In this chapter, we present the major features that most algorithms take into account to efficiently predict miRNA target: seed match, free energy, conservation, target site accessibility, and contribution of multiple binding sites. We also give an overview of the frequently used bioinformatics tools for miRNA target prediction. Understanding the basis of these prediction methodologies may help users to better select the appropriate tools and analyze their output
Bioinformatic tools for microRNA dissection
No full textRecently, microRNAs (miRNAs) have emerged as important elements of gene regulatory networks. MiRNAs are endogenous single-stranded non-coding RNAs (∼22-nt long) that regulate gene expression at the post-transcriptional level. Through pairing with mRNA, miRNAs can down-regulate gene expression by inhibiting translation or stimulating mRNA degradation. In some cases they can also up-regulate the expression of a target gene. MiRNAs influence a variety of cellular pathways that range from development to carcinogenesis. The involvement of miRNAs in several human diseases, particularly cancer, makes them potential diagnostic and prognostic biomarkers. Recent technological advances, especially high-throughput sequencing, have led to an exponential growth in the generation of miRNA-related data. A number of bioinformatic tools and databases have been devised to manage this growing body of data. We analyze 129 miRNA tools that are being used in diverse areas of miRNA research, to assist investigators in choosing the most appropriate tools for their needs
Molecular targets of dietary phytochemicals for possible prevention and therapy of uterine fibroids: Focus on fibrosis
No full textTranilast, an orally active antiallergic compound, inhibits extracellular matrix production in human uterine leiomyoma and myometrial cells
No full textTo determine the effect of tranilast (an antiallergic drug known to suppress fibrosis or to stabilize mast cells) on extracellular matrix production in human leiomyoma and myometrial cells
Locostatin, a disrupter of Raf kinase inhibitor protein, inhibits extracellular matrix production, proliferation, and migration in human uterine leiomyoma and myometrial cells
No full textObjective To investigate the presence of Raf kinase inhibitor protein (RKIP) in human myometrium and leiomyoma as well as to determine the effect of locostatin (RKIP inhibitor) on extracellular matrix (ECM) production, proliferation, and migration in human myometrial and leiomyoma cells. Design Laboratory study. Setting Human myometrium and leiomyoma. Patient(s) Thirty premenopausal women who were admitted to the hospital for myomectomy or hysterectomy. Intervention(s) Myometrial and leiomyoma tissues were used to investigate the localization and the expression level of RKIP through immunohistochemistry and Western blotting. Myometrial and leiomyoma cells were treated with locostatin (10 μM) to measure ECM expression by real-time polymerase chain reaction, GSK3β expression by Western blotting, cell migration by wound-healing assay, and cell proliferation by MTT assay and immunocytochemistry. Main Outcome Measure(s) The expression of RKIP in human myometrial and leiomyoma tissue; ECM components and GSK3β expression, migration, and proliferation in myometrial and leiomyoma cells. Result(s) RKIP is expressed in human myometrial and leiomyoma tissue. Locostatin treatment resulted in the activation of the mitogen-activated protein kinase (MAPK) signal pathway (ERK phosphorylation), providing a powerful validation of our targeting protocol. Further, RKIP inhibition by locostatin reduces ECM components. Moreover, the inhibition of RKIP by locostatin impaired cell proliferation and migration in both leiomyoma and myometrial cells. Finally, locostatin treatment reduced GSK3β expression. Therefore, even if the activation of MAPK pathway should increase proliferation and migration, the destabilization of GSK3β leads to the reduction of proliferation and migration of myometrial and leiomyoma cells. Conclusion(s) Our results indicate that RKIP may be involved in leiomyoma pathophysiology
Extracellular matrix in uterine leiomyoma pathogenesis: a potential target for future therapeutics
Full text linkUterine leiomyoma (also known as fibroid or myoma) is the most common benign tumor of the uterus found in women of reproductive age. It is not usually fatal but can produce serious clinical symptoms, including excessive uterine bleeding, pelvic pain or pressure, infertility and pregnancy complications. Due to lack of effective medical treatments surgery has been a definitive choice for the management of this tumor
Role of activin-A and myostatin and their signaling pathway in human myometrial and leiomyoma cell function.
No full textContext: Uterine leiomyomas are highly prevalent benign tumors of pre-menopausal women and the most common indication for hysterectomy. However, the exact etiology of this tumor is not fully understood. Objective: To evaluate the role of activin-A and myostatin, and their signaling pathways in human myometrial and leiomyoma cells. Design: Laboratory study Setting: Myometrial and leiomyoma cells (primary and cell lines) were cultured in vitro. Patients: The study included premenopausal women who were admitted to the hospital for myomectomy or hysterectomy. Interventions: Primary myometrial and leiomyoma cells and/or cell lines were treated with activin-A (4nM) and myostatin (4nM) for different days of interval (to measure proliferation rate) or 30 min (to measure signaling molecules) or 48 h to measure proliferating markers, extracellular matrix mRNA and/or protein expression by real-time polymerase chain reaction (PCR), western blot and/or immunocytochemistry. Results: We found that activin-A and myostatin significantly reduce cell proliferation in primary myometrial cells but not in leiomyoma cells as measured by CyQUANT cell proliferation assay kit. Reduced expression of PCNA and Ki-67 were also observed in myometrial cells in response to activin-A and myostatin treatment. Activin-A also significantly increased mRNA expression of fibronectin, collagen1A1 and versican in primary leiomyoma cells. Finally, we found that activin-A and myostatin activate Smad2/3 signaling but do not affect Erk or p38 signaling in both myometrial and leiomyoma cells. Conclusions: This study results suggest that activin-A and myostatin can exert antiproliferative and/or fibrotic effects on these cell types via Smad2/3 signaling
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