In Silico Analysis of Regulatory Elements of the Vitamin D Receptor

مستقبل الفيتامين دي (VDR) هو عامل النسخ النووي الذي يتحكم بالتفسير الجيني. تم التوصل إلى أن الضعف في التفسير الجيني يرتبط بأمراض مختلفة. يقوم VDR بمهمة تنظيم مسارات مختلفة مثل التشخيص، الالتهاب وامتصاص الكالسيوم والفوسفات.. إلخ. مع ذلك لا توجد معلومات كافية حول تنظيم الجين نفسه. لذلك فإن فهماً أكثر وضوحاً للعوامل الوراثية والجينية لتنظيم VDR قد يسهل تطور استراتيجيات للوقاية من الأمراض المتعلقة بعوز VDR وعلاجها. ويعتمد هذا البحث على مجموعة من قواعد المعلومات والطرف المستخدمة من أجل تشخيص العناصر الوظيفية المفترضة في VDR. تم تحديد تعديلات هيستون، جزر CpG والعلامات الجينية لـ VDR. وتم رصد سلاسل متكررة، محسنات عوازل ونقاط لربط عوامل النسخ وأهداف جينات VDR بالإضافة إلى تفاعلات بين البروتينات مع الأدوات المعلوماتية الحيوية. وتتداخل بعض هذه العناصر الوراثية مع جزر CpG وأدت الدراسة إلى اكتشاف مقاربة جديدة في مجال الآليات الجزيئية لتنظيم جينات VDR في الخلايا والأنسجة البشرية.Vitamin D receptor (VDR) is a nuclear transcription factor that controls gene expression. Its impaired expression was found to be related to different diseases. VDR also acts as a regulator of different pathways including differentiation, inflammation, calcium and phosphate absorption, etc. but there is no sufficient knowledge about the regulation of the gene itself. Therefore, a better understanding of the genetic and epigenetic factors regulating the VDR may facilitate the improvement of strategies for the prevention and treatment of diseases associated with dysregulation of VDR. In the present investigation, a set of databases and methods were used to identify putative functional elements in the VDR locus. Histone modifications, CpG Islands, epigenetic marks at VDR locus were indicated. In addition, repeated sequences, enhancers, insulators, transcription factor binding sites and targets of the VDR gene, as well as protein-protein interactions with bioinformatics tools, were reported. Some of these genetic elements had overlapped with CpG Islands. These results revealed important new insight into the molecular mechanisms of the VDR gene regulation in human cells and tissues

The role of microRNAs in the pathogenesis of thyroid cancer

Thyroid cancer is the most frequent type of cancers originating from the endocrine system. Early diagnosis leads to good clinical outcome in differentiated types of thyroid cancer. Yet, there are few treatment options for patients with medullary or anaplastic thyroid cancer. Thus, identification of molecular markers that explain the pathologic process during evolution of this cancer has practical significance. MicroRNAs (miRNAs) have been shown to influence the activity of thyroid cancer-related signaling pathways such as MAPK pathway and RET gene. These small transcripts not only can differentiate malignant tissues from non-malignant tissues, but also have differential expression in different stages of thyroid cancer. Assessment of serum levels of miRNAs is a practical noninvasive method for follow-up of patients after thyroidectomy. Moreover, the therapeutic effects of a number of miRNAs have been verified in xenograft models of thyroid cancer. In the current review, we summarize the data regarding the role of miRNAs in thyroid cancer

An update on the molecular mechanisms of ZFAS1 as a prognostic, diagnostic, or therapeutic biomarker in cancers

Abstract Zinc finger antisense 1 (ZFAS1), a newly discovered long noncoding RNA, is expressed in various tissues and organs and has been introduced an oncogenic gene in human malignancies. In various cancers, ZFAS1 regulates apoptosis, cell proliferation, the cell cycle, migration, translation, rRNA processing, and spliceosomal snRNP assembly; targets signaling cascades; and interacts with transcription factors via binding to key proteins and miRNAs, with conflicting findings on its effect on these processes. ZFAS1 is elevated in different types of cancer, like colorectal, colon, osteosarcoma, and gastric cancer. Considering the ZFAS1 expression pattern, it also has the potential to be a diagnostic or prognostic marker in various cancers. The current review discusses the mode of action of ZFAS1 in various human cancers and its regulation function related to chemoresistance comprehensively, as well as the potential role of ZFAS1 as an effective and noninvasive cancer-specific biomarker in tumor diagnosis, prognosis, and treatment. We expected that the current review could fill the current scientific gaps in the ZFAS1-related cancer causative mechanisms and improve available biomarkers

DNA methylation signature as a biomarker of major neuropsychiatric disorders

DNA methylation is a broadly-investigated epigenetic modification that has been considered as a heritable and reversible change. Previous findings have indicated that DNA methylation regulates gene expression in the central nervous system (CNS). Also, disturbance of DNA methylation patterns has been associated with destructive consequences that lead to human brain diseases such as neuropsychiatric disorders (NPDs). In this review, we comprehensively discuss the mechanism and function of DNA methylation and its most recent associations with the pathology of NPDs-including major depressive disorder (MDD), schizophrenia (SZ), autism spectrum disorder (ASD), bipolar disorder (BD), and attention/deficit hyperactivity disorder (ADHD). We also discuss how heterogeneous findings demand further investigations. Finally, based on the recent studies we conclude that DNA methylation status may have implications in clinical diagnostics and therapeutics as a potential epigenetic biomarker of NPDs

Reduction of GAS5 and FOXD3-AS1 long non-coding RNAs in patients with bipolar disorder

Abstract Bipolar disorder (BD) patients suffer from severe disability and premature death because of failure in prognosis, diagnosis, and treatment. Although neural mechanisms of bipolar have not been fully discovered, studies have shown long noncoding RNAs (lncRNAs) can play an important role in signaling pathways such as PI3K/AKT pathway. There has been little study on deregulated lncRNAs and the lncRNAs’ mode of action in the BD. Hence, we aimed to investigate the expression of PI3K/AKT pathway-related lncRNAs named TUG1, GAS5, and FOXD3-AS1 lncRNAs in the PMBC in 50 bipolar patients and 50 healthy controls. Our results showed that FOXD3-AS1 and GAS5 under-expressed significantly in bipolar patients compared to healthy controls (P = 0.0028 and P < 0.0001 respectively). Moreover, after adjustment, all P values remained significant (q value < 0.0001). According to the ROC curve, AUC (area under the curve), specificity, and sensitivity of these lncRNAs, GAS5 and FOXD3-AS1 might work as BD candidate diagnostic biomarkers. Taken together, the current results highlight that the dysregulation of FOXD3-AS1 and GAS5 may be associated with an increased risk of BD