The Role of Extracellular Matrix Proteins on Epithelial to Mesenchymal Transition in Glioblastoma Multiforme

Glioblastoma multiforme (GBM) is the most common primary brain tumor in humans and is characterized as being highly aggressive and invasive, with the ability to locally invade different areas of the central nervous system (CNS). GBM local invasion undergoes an epithelial to mesenchmal like (EMT) process characterized by the loss of cell-cell adhesion and increased cell mobility. The EMT-like switch in GBM is triggered by a single transcription factor, Twist1, and is characterized by the loss of cell clustering, re-organization of the basement membrane, and increased cell migration. GBM invasion depends on the remodeling of the extracellular matrix (ECM) microenvironment, which is induced in part by activated matrix metalloproteinases (MMPs). MMPs have proteolytic activity, acting in the breakdown of the basement membrane (BM), and facilitating cell proliferation, adhesion, migration and angiogenesis. The progression of GBM tumor malignancy is a multistep process that involves cell-cell and cell-ECM adhesion, invasion and migration. In this study, we examined the ability of the neural ECM proteins vitronectin, fibronectin, laminin and collagen IV to trigger an EMT-like response in GBM. We found that, monolayer formation of GBM cells on purified ECM proteins exhibited the mesenchymal phenotype, but this did not lead to the induction of the transcription factor Twist1, a marker used to determine GBM invasion. On the contrary, we found that GBM cells grown on collagen IV show heightened levels of Twist without the EMT-like switch in morphologies. These findings suggest an important role for collagen IV in the process of GBM local invasion

Parkinson’s Disease-related Circulating microRNA Biomarkers - a Validation Study

Parkinson’s disease (PD) is the second most common neurodegenerative disease. One of the major challenges in studying this progressive neurological disorder is to identify and develop biomarkers for early detection. Recently, several blood-based microRNA (miRNA) biomarkers for PD have been reported. However, follow-up studies with new, independent cohorts have been rare. Previously, we identified a panel of four circulating miRNA biomarkers for PD (miR-1826, miR-450b-3p, miR-505, and miR-626) with biomarker performance of 91% sensitivity and 100% specificity. However, the expression of miR-450b-3p could not be detected in a new, independent validation set. In our current study, we improved the detection power by including a non-biased pre-amplification step in quantitative real-time PCR (qRT-PCR) and reevaluated the biomarker performance. We found the panel of four PD-related miRNAs achieved the predictive power of 83% sensitivity and 75% specificity in our validation set. This is the first biomarker validation study of PD which showed reproducibility and robustness of plasma-based circulating miRNAs as molecular biomarkers and qRT-PCR as potential diagnostic assay

Parkinson’s Disease-related Circulating microRNA Biomarkers - a Validation Study

Parkinson’s disease (PD) is the second most common neurodegenerative disease. One of the major challenges in studying this progressive neurological disorder is to identify and develop biomarkers for early detection. Recently, several blood-based microRNA (miRNA) biomarkers for PD have been reported. However, follow-up studies with new, independent cohorts have been rare. Previously, we identified a panel of four circulating miRNA biomarkers for PD (miR-1826, miR-450b-3p, miR-505, and miR-626) with biomarker performance of 91% sensitivity and 100% specificity. However, the expression of miR-450b-3p could not be detected in a new, independent validation set. In our current study, we improved the detection power by including a non-biased pre-amplification step in quantitative real-time PCR (qRT-PCR) and reevaluated the biomarker performance. We found the panel of four PD-related miRNAs achieved the predictive power of 83% sensitivity and 75% specificity in our validation set. This is the first biomarker validation study of PD which showed reproducibility and robustness of plasma-based circulating miRNAs as molecular biomarkers and qRT-PCR as potential diagnostic assay

Cross-talk Between Alzheimer\u27s and Parkinson\u27s Disease: Evaluation of microRNA Expressions

Alzheimer\u27s disease (AD) is the most common neurodegenerative disease followed by Parkinson’s disease (PD). There is no cure for AD or PD and definitive diagnosis of these devastating diseases is achieved by autopsy. Although AD and PD are distinct clinical conditions, emerging evidence has shown pathological similarities between these two disorders, such as cognitive impairment and aggregation of misfolded proteins, suggests cross­disease association. MicroRNAs (miRNAs) are a class of small, non­coding RNA molecules that are involved in many essential biological processes such as cell development and differentiation. Recently, miRNAs have been found to distinguished PD patients from neurologically healthy controls. In this project, we investigate the gene expression of PD­related miRNAs on AD brain samples to shed light on the similarity between AD and PD