Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bipolar disorder (BD), characterized by recurrent mood swings between depression and mania, is a highly heritable and devastating mental illness with poorly defined pathophysiology. Recent genome-wide molecular genetic studies have identified several protein-coding genes and microRNAs (miRNAs) significantly associated with BD. Notably, some of the proteins expressed from BD-associated genes function in neuronal synapses, suggesting that abnormalities in synaptic function could be one of the key pathogenic mechanisms of BD. In contrast, however, the role of BD-associated miRNAs in disease pathogenesis remains largely unknown, mainly because of a lack of understanding about their target mRNAs and pathways in neurons. To address this problem, in this study, we focused on a recently identified BD-associated but uncharacterized miRNA, miR-1908-5p. We identified and validated its novel target genes including DLGAP4, GRIN1, STX1A, CLSTN1 and GRM4, which all function in neuronal glutamatergic synapses. Moreover, bioinformatic analyses of human brain expression profiles revealed that the expression levels of miR-1908-5p and its synaptic target genes show an inverse-correlation in many brain regions. In our preliminary experiments, the expression of miR-1908-5p was increased after chronic treatment with valproate but not lithium in control human neural progenitor cells. In contrast, it was decreased by valproate in neural progenitor cells derived from dermal fibroblasts of a BD subject. Together, our results provide new insights into the potential role of miR-1908-5p in the pathogenesis of BD and also propose a hypothesis that neuronal synapses could be a key converging pathway of some BD-associated protein-coding genes and miRNAs.
 ...
PMID:Bipolar Disorder Associated microRNA, miR-1908-5p, Regulates the Expression of Genes Functioning in Neuronal Glutamatergic Synapses. 2803 80

To investigate the role of circular RNA DLGAP4 (circDLGAP4) in lung cancer. circDLGAP4 expression was detected in lung cancer tissues and cell lines by PCR. The correlation between circDLGAP4 and clinicopathological characteristics of lung cancer patients was investigated. Moreover, the influences of depression of circDLGAP4 on the biological processes biological processes of lung cancer cells were explored in vitro. In addition, whether circDLGAP4 regulated lung cancer cell biological processes by sponging microRNA-143 (miR-143) to regulate cyclin-dependent kinase 1 (CDK1) expression was explored and verified in another lung cell line. CircDLGAP4 expression was remarkably elevated in lung cancer tissues and was significantly corrected with TNM stage and tumor metastasis. Suppression of circDLGAP4 inhibited the biological performances of lung cancer cells. Also, there was a negative regulatory relationship between circDLGAP4 and miR-143. Inhibition of miR-143 alleviated the influences of circDLGAP4 depression on lung cancer cell biological processes. Moreover, CDK1 was discovered as a target of miR-143, and miR-143 was involved in the process of lung cancer cell biological processes through targeting CDK1. Our findings reveal that circular RNA circDLGAP4 is involved in lung cancer development through modulating microRNA-143/CDK1 axis. circDLGAP4 may serve as a potential biomarker for the diagnosis or treatment of lung cancer.
 ...
PMID:Circular RNA circDLGAP4 is involved in lung cancer development through modulating microRNA-143/CDK1 axis. 3264 40