MicroRNAs: exploring a new dimension in the pathogenesis of kidney cancer

Renal cell carcinoma (RCC) is the most common neoplasm of the adult kidney. The role of the von-Hippel-Lindeau (VHL) tumour suppressor gene is well established in RCC with a loss of VHL protein leading to accumulated hypoxia-induced factor (HIF) and the subsequent transcriptional activation of multiple downstream targets. Recently, microRNAs (miRNAs) have been shown to be differentially expressed in RCC and their role in RCC pathogenesis is emerging. This month, in BMC Medicine, Gleadle and colleagues show that certain miRNAs are regulated by VHL in either a hypoxia-inducible factor (HIF)-dependent or HIF-independent manner in RCC. They also show that miRNA expression correlates with the survival of RCC patients

MicroRNA-22 Regulates Hypoxia Signaling in Colon Cancer Cells

MicroRNAs (MiRNAs) are short, non-coding RNA that regulate a variety of cellular functions by suppressing target protein expression. We hypothesized that a set of microRNA regulate tumor responses to hypoxia by inhibiting components of the hypoxia signaling pathway. We found that miR-22 expression in human colon cancer is lower than in normal colon tissue. We also found that miR-22 controls hypoxia inducible factor 1α (HIF-1α) expression in the HCT116 colon cancer cell line. Over-expression of miR-22 inhibits HIF-1α expression, repressing vascular endothelial growth factor (VEGF) production during hypoxia. Conversely, knockdown of endogenous miR-22 enhances hypoxia induced expression of HIF-1α and VEGF. The conditioned media from cells over-expressing miR-22 contain less VEGF protein than control cells, and also induce less endothelial cell growth and invasion, suggesting miR-22 in adjacent cells influences endothelial cell function. Taken together, our data suggest that miR-22 might have an anti-angiogenic effect in colon cancer

The Contribution of High Levels of Somatic Symptom Severity to Sickness Absence Duration, Disability and Discharge

Introduction: The primary objectives were to compare the duration of sickness absence in employees with high levels of somatic symptom severity (HLSSS) with employees with lower levels of somatic symptom severity, and to establish the long-term outcomes concerning return to work (RTW), disability and discharge. Secondary objective was to evaluate determinants of the duration of sickness absence in employees with HLSSS. Methods: 489 sick-listed employees registered with five Occupational Health Physician (OHP) group practices were included in this study. We measured their baseline scores for somatic symptoms severity, depressive disorders, anxiety disorders, health anxiety, distress and functional impairment. The OHPs filled in a questionnaire on their diagnosis. A prospective 2-year follow-up was carried out to assess the long-term outcomes concerning sickness absence, and retrospective information was gathered with regard to sickness absence during the 12 months before the employees were sick-listed. Results: The median duration of sickness absence was 78 days longer for employees with HLSSS. They more often remained disabled and were discharged more often, especially due to problems in the relationship between the employer and the employee. HLSSS, health anxiety and older age contributed to a longer duration of sickness absence of employees. Conclusion: High levels of somatic symptom severity are a determinant of prolonged sickness absence, enduring disabilities and health-related job loss. Occupational health physicians should identify employees who are at risk and adhere to guidelines for medically unexplained somatic symptoms

Regulation of microRNA biogenesis and turnover by animals and their viruses

Item does not contain fulltextMicroRNAs (miRNAs) are a ubiquitous component of gene regulatory networks that modulate the precise amounts of proteins expressed in a cell. Despite their small size, miRNA genes contain various recognition elements that enable specificity in when, where and to what extent they are expressed. The importance of precise control of miRNA expression is underscored by functional studies in model organisms and by the association between miRNA mis-expression and disease. In the last decade, identification of the pathways by which miRNAs are produced, matured and turned-over has revealed many aspects of their biogenesis that are subject to regulation. Studies in viral systems have revealed a range of mechanisms by which viruses target these pathways through viral proteins or non-coding RNAs in order to regulate cellular gene expression. In parallel, a field of study has evolved around the activation and suppression of antiviral RNA interference (RNAi) by viruses. Virus encoded suppressors of RNAi can impact miRNA biogenesis in cases where miRNA and small interfering RNA pathways converge. Here we review the literature on the mechanisms by which miRNA biogenesis and turnover are regulated in animals and the diverse strategies that viruses use to subvert or inhibit these processes