Medicine and Health Sciences Commons^™

Racial Differences In Human Platelet Par4 Reactivity Reflect Expression Of Pctp And Mir-376c., Leonard Edelstein, Lukas M Simon, Raúl Teruel Montoya, Michael Holinstat, Edward S Chen, Angela Bergeron, Xianguo Kong, Srikanth Nagalla, Narla Mohandas, David E Cohen, Jing-Fei Dong, Chad Shaw, Paul Bray

Cardeza Foundation for Hematologic Research

Racial differences in the pathophysiology of atherothrombosis are poorly understood. We explored the function and transcriptome of platelets in healthy black (n = 70) and white (n = 84) subjects. Platelet aggregation and calcium mobilization induced by the PAR4 thrombin receptor were significantly greater in black subjects. Numerous differentially expressed RNAs were associated with both race and PAR4 reactivity, including PCTP (encoding phosphatidylcholine transfer protein), and platelets from black subjects expressed higher levels of PC-TP protein. PC-TP inhibition or depletion blocked PAR4- but not PAR1-mediated activation of platelets and megakaryocytic cell lines. miR-376c levels were differentially expressed by race and …

Microrna-200c Modulates The Expression Of Muc4 And Muc16 By Directly Targeting Their Coding Sequences In Human Pancreatic Cancer., Prakash Radhakrishnan, Ashley M. Mohr, Paul M. Grandgenett, Maria M. Steele, Surinder K. Batra, Michael A. Hollingsworth

Journal Articles: Biochemistry & Molecular Biology

Transmembrane mucins, MUC4 and MUC16 are associated with tumor progression and metastatic potential in human pancreatic adenocarcinoma. We discovered that miR-200c interacts with specific sequences within the coding sequence of MUC4 and MUC16 mRNAs, and evaluated the regulatory nature of this association. Pancreatic cancer cell lines S2.028 and T3M-4 transfected with miR-200c showed a 4.18 and 8.50 fold down regulation of MUC4 mRNA, and 4.68 and 4.82 fold down regulation of MUC16 mRNA compared to mock-transfected cells, respectively. A significant reduction of glycoprotein expression was also observed. These results indicate that miR-200c overexpression regulates MUC4 and MUC16 mucins in pancreatic …

Cytotoxic Lymphocyte Micrornas As Prospective Biomarkers For Chronic Fatigue Syndrome/Myalgic Encephalomyelitis, Ekua Brenu, Kevin Ashton, Mieke Van Driel, Donald Staines, Daniel Peterson, Gunn Atkinson, Sonia Marshall-Gradisnika

Kevin Ashton

Background: Immune dysfunction associated with a disease often has a molecular basis. A novel group of molecules known as microRNAs (miRNAs) have been associated with suppression of translational processes involved in cellular development and proliferation, protein secretion, apoptosis, immune function and inflammatory processes. MicroRNAs may be implicated in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME), where immune function is impaired. The objective of this study was to determine the association between miRNAs in cytotoxic cells and CFS/ME. Methods: Natural Killer (NK) and CD8+T cells were preferentially isolated from peripheral blood mononuclear cells from all participants (CFS/ME, n = 28; mean age = …

Alcohol Facilitates Hcv Rna Replication Via Up-Regulation Of Mir-122 Expression And Inhibition Of Cyclin G1 In Human Hepatoma Cells, Wei Hou, Terence Bukong, Karen Kodys, Gyongyi Szabo

Gyongyi Szabo

BACKGROUND: Clinical studies demonstrate synergistic liver damage by alcohol and hepatitis C virus (HCV); however, the mechanisms by which alcohol promotes HCV infection remain obscure. The liver-specific microRNA-122 (miR-122) regulates HCV replication and expression of host genes, including Cyclin G1. Here, we hypothesized that alcohol regulates miR-122 expression and thereby modulates HCV RNA replication. METHODS: The J6/JFH/Huh-7.5 model of HCV infection was used in this study. Real-time quantitative polymerase chain reaction, Western blotting, electrophoretic mobility shift assay, and confocal microscopy were used for experimental analysis. RESULTS: We found that acute alcohol exposure (25 mM) significantly increased intracellular HCV RNA as …

Preeclampsia And Micrornas, Eric J. Devor, Donna A. Santillan, Mark K. Santillan

Donna A. Santillan

Preeclampsia is a critical gestational condition that threatens the life of both mother and child. One of the most serious aspects of preeclampsia hampering both clinical management and scientific understanding is that there are, as yet, no early warning signs or risk markers. The discovery of microRNAs (miRNAs), tiny post-transcriptional regulators of gene expression, offers potentially fertile ground for developing such markers. The current state of knowledge about miRNAs in preeclampsia is presented along with information regarding miRNA detection in peripheral fluids that could lead to minimally invasive risk assessment.

Preeclampsia And Micrornas, Eric J. Devor, Donna A. Santillan, Mark K. Santillan

Mark K. Santillan

Preeclampsia is a critical gestational condition that threatens the life of both mother and child. One of the most serious aspects of preeclampsia hampering both clinical management and scientific understanding is that there are, as yet, no early warning signs or risk markers. The discovery of microRNAs (miRNAs), tiny post-transcriptional regulators of gene expression, offers potentially fertile ground for developing such markers. The current state of knowledge about miRNAs in preeclampsia is presented along with information regarding miRNA detection in peripheral fluids that could lead to minimally invasive risk assessment.

Micrornas In Liver Disease, Gyongyi Szabo, Shashi Bala

Gyongyi Szabo

Small, noncoding microRNAs (miRNAs) regulate diverse biological functions in the liver and increasing evidence suggests that they have a role in liver pathology. This Review summarizes advances in the field of miRNAs in liver diseases, inflammation and cirrhosis. MicroRNA-122, the most abundant miRNA in hepatocytes, has well-defined roles in HCV replication, and data indicate that it also serves as a viable therapeutic target. The role of miR-122 is also emerging in other liver diseases. Ample evidence exists for the important regulatory potential of other miRNAs in conditions associated with liver inflammation related to alcohol use, the metabolic syndrome or autoimmune …

Preeclampsia And Micrornas, Eric J. Devor, Donna A. Santillan, Mark K. Santillan

Eric J Devor

Preeclampsia is a critical gestational condition that threatens the life of both mother and child. One of the most serious aspects of preeclampsia hampering both clinical management and scientific understanding is that there are, as yet, no early warning signs or risk markers. The discovery of microRNAs (miRNAs), tiny post-transcriptional regulators of gene expression, offers potentially fertile ground for developing such markers. The current state of knowledge about miRNAs in preeclampsia is presented along with information regarding miRNA detection in peripheral fluids that could lead to minimally invasive risk assessment.

A Study Of Small Rnas From Cerebral Neocortex Of Pathology-Verified Alzheimer's Disease, Dementia With Lewy Bodies, Hippocampal Sclerosis, Frontotemporal Lobar Dementia, And Non-Demented Human Controls, Sébastien S. Hébert, Wang-Xia Wang, Qi Zhu, Peter T. Nelson

Sanders-Brown Center on Aging Faculty Publications

MicroRNAs (miRNAs) are small (20-22 nucleotides) regulatory non-coding RNAs that strongly influence gene expression. Most prior studies addressing the role of miRNAs in neurodegenerative diseases (NDs) have focused on individual diseases such as Alzheimer's disease (AD), making disease-to-disease comparisons impossible. Using RNA deep sequencing, we sought to analyze in detail the small RNAs (including miRNAs) in the temporal neocortex gray matter from non-demented controls (n = 2), AD (n = 5), dementia with Lewy bodies (n = 4), hippocampal sclerosis of aging (n = 4), and frontotemporal lobar dementia (FTLD) (n = 5) cases, together accounting for the most prevalent …

Chronic Ethanol Feeding Alters Mirna Expression Dynamics During Liver Regeneration., Rachael P Dippold, Rajanikanth Vadigepalli, Gregory E. Gonye, Biswanath Patra, Jan B. Hoek

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: Adaptation to chronic ethanol (EtOH) treatment of rats results in a changed functional state of the liver and greatly inhibits its regenerative ability, which may contribute to the progression of alcoholic liver disease.

METHODS: In this study, we investigated the effect of chronic EtOH intake on hepatic microRNA (miRNA) expression in male Sprague-Dawley rats during the initial 24 hours of liver regeneration following 70% partial hepatectomy (PHx) using miRNA microarrays. miRNA expression during adaptation to EtOH was investigated using RT-qPCR. Nuclear factor kappa B (NFκB) binding at target miRNA promoters was investigated with chromatin immunoprecipitation.

RESULTS: Unsupervised clustering of …

Clinical Consequences Of Micrornas In Colorectal Cancer, Liselle C. Bovell

All ETDs from UAB

Colorectal cancer (CRC) is a heterogeneous disease, and factors such as tumor location, the environment, genetics, and ethnic differences, can influence its development and progression. Over the last few decades, overall CRC mortality rates have declined; however, racial disparities in mortality rates have increased. The discovery of biomarkers that focus on identifying individual differences based on confounders such as tumor stage and patient race/ethnicity is needed, for such biomarkers can lead to development of personalized therapeutic approaches to target these molecules. MicroRNAs (miRNAs) are a class of small molecules that regulate genes at the post-transcriptional level. Altered miRNA expression levels …