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Shingo Matsushima, Junichi Ishiyama
MicroRNAs play an important role in the development and progression of various diseases, such as idiopathic pulmonary fibrosis (IPF). Although the accumulation of aberrant fibroblasts resistant to apoptosis is a hallmark in IPF lungs, the mechanism regulating apoptosis susceptibility is not fully understood. Here, we investigated the role of miR-29, which is the most downregulated microRNA in IPF lungs and is also known as a regulator of extracellular matrix (ECM), in the mechanism of apoptosis resistance. We found that functional inhibition of miR-29c caused resistance to Fas-mediated apoptosis in lung fibroblasts...
October 7, 2016: American Journal of Physiology. Lung Cellular and Molecular Physiology
Kamil Duris, Jolana Lipkova
BACKGROUND: Stroke is the second leading cause of death worldwide. Understanding of gene expression dynamics could bring new approaches in diagnostics and therapy of stroke. Small noncoding molecules termed "microRNA" represent the most flexible network of gene expression regulators. METHODS: The aim of this review was to briefly describe the structure and function of microRNA and summarize the current knowledge about the involvement of microRNAs in the pathophysiology of ischemic and hemorrhagic stroke based on both experimental and clinical studies...
September 19, 2016: Current Drug Delivery
Edgard Verdura, Dominique Hervé, Françoise Bergametti, Clémence Jacquet, Typhaine Morvan, Carol Prieto-Morin, Alexandre Mackowiak, Eric Manchon, Hassan Hosseini, Charlotte Cordonnier, Isabelle Girard-Buttaz, Sophie Rosenstingl, Christian Hagel, Gregor Kuhlenbaümer, Elena Leca-Radu, Didier Goux, Lauren Fleming, Tom Van Agtmael, Hugues Chabriat, Françoise Chapon, Elisabeth Tournier-Lasserve
OBJECTIVE: Cerebral small vessel disease (cSVD) is an heterogeneous group of disorders. Screening of known cSVD genes identifies the causative mutation in less than 15% of familial cSVD cases. We sought to identify novel causes of cSVD. METHODS: We used linkage analysis and exome sequencing to identify the causal mutation in a French cSVD family. The identified candidate gene was then screened in 202 cSVD unrelated probands, including one proband from the first reported Pontine Autosomal Dominant MicroAngiopathy with Leukoencephalopathy (PADMAL) family...
September 26, 2016: Annals of Neurology
C-Y Wang, J-B Ren, M Liu, L Yu
OBJECTIVE: Recent studies have shown that high miR-29 expression was associated with poor prognosis in patients with osteosarcoma (OS). However, the exact role and mechanisms of miR-29 in human OS remains speculative. Here, we identify a connection between miR-29 and TGF-β1/PUMA signaling in this context. PATIENTS AND METHODS: MG-63 cells were treated with anti-miR-29 for 48 h. Cell growth and apoptosis in vitro were detected by MTT, colony formation and flow cytometry assay...
September 2016: European Review for Medical and Pharmacological Sciences
Lingqian Chang, Daniel Gallego-Perez, Chi-Ling Chiang, Paul Bertani, Tairong Kuang, Yan Sheng, Feng Chen, Zhou Chen, Junfeng Shi, Hao Yang, Xiaomeng Huang, Veysi Malkoc, Wu Lu, Ly James Lee
While electroporation has been widely used as a physical method for gene transfection in vitro and in vivo, its application in gene therapy of cardiovascular cells remains challenging. Due to the high concentration of ion-transport proteins in the sarcolemma, conventional electroporation of primary cardiomyocytes tends to cause ion-channel activation and abnormal ion flux, resulting in low transfection efficiency and high mortality. In this work, a high-throughput nanoelectroporation technique based on a nanochannel array platform is reported, which enables massively parallel delivery of genetic cargo (microRNA, plasmids) into mouse primary cardiomyocytes in a controllable, highly efficient, and benign manner...
September 20, 2016: Small
Adonis Sfera, Carolina Osorio, Luzmin Inderias, Michael Cummings
BACKGROUND: Exposed to antipsychotic drugs (APDs), older individuals with dementing illness are at risk of cerebrovascular adverse effects (CVAE), including sudden death. Transient microvascular dysfunctions are known to occur in younger persons exposed to APDs; however, they seldom progress to CVAE, suggesting that APDs alone are insufficient for engendering this untoward effect. It is, therefore, believed that a preexistent microvascular damage is necessary for CVAE to take place, but the exact nature of this lesion remains unclear...
2016: Frontiers in Endocrinology
N Schlabritz-Loutsevitch, K Apostolakis-Kyrus, R Krutilina, G Hubbard, M Kocak, Z Janjetovic, S Sathanandam, A T Slominski, G Mari, E Dick
BACKGROUND: Obesity in pregnancy (MO) is a risk factor for maternal and/or fetal cardiovascular system disorders. This study evaluated maternal CVS expression of microRNA-29 family and its target molecules in MO to test the hypotheses: CVS miR-29 concentrations are increased in pregnancy and decreased in MO. METHODS: Non-pregnant (n=4), pregnant obese (POb, n=4), and pregnant non-obese (PnOb, n=4) baboons (Papio spp.) were studied. Maternal left ventricle (LV), left atrium (LA), and aortic arch (AA) were collected at the end of gestation...
September 15, 2016: Journal of Medical Primatology
Jason J Kwon, Jeffrey A Willy, Kayla A Quirin, Ronald C Wek, Murray Korc, Xiao-Ming Yin, Janaiah Kota
Pancreatic Ductal Adenocarcinoma (PDAC) is a highly lethal malignancy that responds poorly to current therapeutic modalities. In an effort to develop novel therapeutic strategies, we found downregulation of miR-29 in pancreatic cancer cells, and overexpression of miR-29a sensitized chemotherapeutic resistant pancreatic cancer cells to gemcitabine, reduced cancer cell viability, and increased cytotoxicity. Furthermore, miR-29a blocked autophagy flux, as evidenced by an accumulation of autophagosomes and autophagy markers, LC3B and p62, and a decrease in autophagosome-lysosome fusion...
September 10, 2016: Oncotarget
Paolo Giuffrida, Massimo Pinzani, Gino R Corazza, Antonio Di Sabatino
Intestinal fibrosis, caused by an excessive deposition of extracellular matrix components, and subsequent stricture development are a common complication of inflammatory bowel disease. However, currently there are no biomarkers which reliably predict the risk of developing intestinal strictures or identify early stages of fibrosis prior to clinical symptoms. Candidate biomarkers of intestinal fibrosis, including gene variants (i.e. nucleotide-binding oligomerization domain-2 gene), serum microRNAs (miR-19, miR-29), serum extracellular matrix proteins (i...
August 2016: United European Gastroenterology Journal
Weiwei Luo, Xiao Liang, Songqian Huang, Xiaojuan Cao
Vascular endothelial growth factor A (VEGFA) is the most studied and the best characterized member of the VEGF family and is a key regulator of angiogenesis via its ability to affect the proliferation, migration, and differentiation of endothelial cells. In this study, the full-length cDNAs encoding VEGFAa and VEGFAb from pond loach, Misgurnus anguillicaudatus, were isolated. The VEGFAa is constituted by an open reading frame (ORF) of 570bp encoding for a peptide of 189 amino acid residues, a 639bp 5'-untranslated region (UTR) and a 2383bp 3' UTR...
August 8, 2016: Comparative Biochemistry and Physiology. Part B, Biochemistry & Molecular Biology
Tetsuya Toyono, Tomohiko Usui, Guadalupe Villarreal, Laura Kallay, Mario Matthaei, Lucas M M Vianna, Angela Y Zhu, Masahiko Kuroda, Shiro Amano, Albert S Jun
PURPOSE: MicroRNAs are small noncoding RNAs that regulate gene expression at the posttranscriptional level. We reported that levels of microRNA (miR)-29 family are decreased in corneas of patients with Fuchs endothelial corneal dystrophy (FECD). The miR-29 family regulates the production of extracellular matrix (ECM) proteins. Accumulation of ECM proteins in Descemet membrane is an important pathologic change in FECD. In this study, we transfected miR-29b into human corneal endothelial cells and tissues and evaluated ECM protein expression levels...
November 2016: Cornea
Peng Ru, Peng Hu, Feng Geng, Xiaokui Mo, Chunming Cheng, Ji Young Yoo, Xiang Cheng, Xiaoning Wu, Jeffrey Yunhua Guo, Ichiro Nakano, Etienne Lefai, Balveen Kaur, Arnab Chakravarti, Deliang Guo
Dysregulated lipid metabolism is a characteristic of malignancies. Sterol regulatory element binding protein 1 (SREBP-1), a transcription factor playing a central role in lipid metabolism, is highly activated in malignancies. Here, we unraveled a link between miR-29 and the SCAP (SREBP cleavage-activating protein)/SREBP-1 pathway in glioblastoma (GBM) growth. Epidermal growth factor receptor (EGFR) signaling enhances miR-29 expression in GBM cells via upregulation of SCAP/SREBP-1, and SREBP-1 activates miR-29 expression via binding to specific sites in its promoter...
August 9, 2016: Cell Reports
Z-G Zuo, X-F Zhang, X-Z Ye, Z-H Zhou, X-B Wu, S-C Ni, H-Y Song
OBJECTIVE: RNA-seq data of rectal adenocarcinoma (READ) were analyzed with bioinformatics tools to unveil potential biomarkers in the disease. MATERIALS AND METHODS: RNA-seq data of READ were downloaded from The Cancer Genome Atlas (TCGA) database. Differential analysis was performed with package edgeR. False discovery rate (FDR) < 0.05 and |log2 (fold change)|>1 were set as cut-off values to screen out differentially expressed genes (DEGs). Gene coexpression network was constructed with package Ebcoexpress...
July 2016: European Review for Medical and Pharmacological Sciences
Yanhua Cui, Ting Li, Dehua Yang, Song Li, Weidong Le
The ten-eleven translocation-1 (Tet1), which converts 5-methylcytosine (5mC) to 5-hydroxymethycytosine (5hmC), plays important roles in many important biological processes, such as mouse embryonic stem cells (ESCs) maintenance. However, the mechanisms for Tet-1 regulation remain largely unknown. Here we showed that miR-29 family (miR-29a, miR-29b and miR-29c) can directly repress Tet1 expression. We found that Tet1 was highly expressed and 5hmC was presented at relatively high levels in mouse ESCs, but the levels of both Tet1 and 5hmC were reduced during the early differentiation of ESCs...
July 21, 2016: Oncotarget
Ryan M Spengler, Xiaoming Zhang, Congsheng Cheng, Jared M McLendon, Jessica M Skeie, Frances L Johnson, Beverly L Davidson, Ryan L Boudreau
MicroRNAs (miRs) have emerged as key biological effectors in human health and disease. These small noncoding RNAs are incorporated into Argonaute (Ago) proteins, where they direct post-transcriptional gene silencing via base-pairing with target transcripts. Although miRs have become intriguing biological entities and attractive therapeutic targets, the translational impacts of miR research remain limited by a paucity of empirical miR targeting data, particularly in human primary tissues. Here, to improve our understanding of the diverse roles miRs play in cardiovascular function and disease, we applied high-throughput methods to globally profile miR:target interactions in human heart tissues...
September 6, 2016: Nucleic Acids Research
Eriona Hysolli, Yoshiaki Tanaka, Juan Su, Kun-Yong Kim, Tianyu Zhong, Ralf Janknecht, Xiao-Ling Zhou, Lin Geng, Caihong Qiu, Xinghua Pan, Yong-Wook Jung, Jijun Cheng, Jun Lu, Mei Zhong, Sherman M Weissman, In-Hyun Park
Reprogramming to pluripotency after overexpression of OCT4, SOX2, KLF4, and MYC is accompanied by global genomic and epigenomic changes. Histone modification and DNA methylation states in induced pluripotent stem cells (iPSCs) have been shown to be highly similar to embryonic stem cells (ESCs). However, epigenetic differences still exist between iPSCs and ESCs. In particular, aberrant DNA methylation states found in iPSCs are a major concern when using iPSCs in a clinical setting. Thus, it is critical to find factors that regulate DNA methylation states in reprogramming...
July 12, 2016: Stem Cell Reports
Akiyoshi Chikenji, Hitoshi Ando, Megumi Nariyama, Takeo Suga, Ryohei Iida, Kazuhiro Gomi
Skeletal myogenesis is regulated by a considerable number of microRNAs (miRNAs). miRNA regulatory networks are complicated, and details of how they operate remain unclear. In this study, MTT assays confirmed that miR-29a is the most effective miR-29 paralog. Microarray analysis demonstrated upregulation of ten-eleven translocation enzyme-1 (Tet1) mRNA in response to miR-29a inhibition in C2C12 murine myoblast cells. We investigated the factors acting downstream in the miR-29a-Tet1 signal pathway using real-time RT-PCR...
2016: Journal of Oral Science
Michael Vanden Oever, Daniel Muldoon, Wendy Mathews, Ron McElmurry, Jakub Tolar
Recessive dystrophic epidermolysis bullosa (RDEB) is a complex inherited skin disorder caused by loss-of-function mutations in the COL7A1 gene. For an effective treatment of this disorder to be realized, both a thorough understanding of the regulation of COL7A1 and an understanding of the underlying nature of the complications of RDEB are needed. Currently, both posttranscriptional regulation of COL7A1 and the underlying causes of fibrosis in RDEB patients are poorly understood. Here, we describe a mechanism of regulation, to our knowledge previously unknown, by which micro RNA-29 (miR-29) regulates COL7A1 in a complex network: both directly through targeting its 3' untranslated region at two distinct seed regions and indirectly through targeting an essential transcription factor required for basal COL7A1 expression, SP1...
October 2016: Journal of Investigative Dermatology
Chunli Liang, Shurui Bu, Xiaoming Fan
The microRNA (miR)-29 family is closely associated with fibrotic processes by virtue of its low expression in many tissues during organ fibrosis. The present study investigated whether miR-29b overexpression suppressed hepatic stellate cell (HSC) activation and its interactions with transforming growth factor (TGF)-β1/mothers against decapentaplegic homolog 3 (Smad3), a classical signal transduction pathway contributing to the activation of HSCs. The results showed that transfection of LX-2 (human HSC) cells with miR-29b mimic or pSUPER-Smad3 silencing (si)RNA resulted in significantly increased expression of miR-29b and decreased expression of Smad3...
July 2016: Cell Biochemistry and Function
Wei Guo, Houda Benlhabib, Carole R Mendelson
Lung alveolar type II cells uniquely synthesize surfactant, a developmentally regulated lipoprotein that is essential for breathing. Expression of the gene (SFTPA) encoding the major surfactant protein, SP-A, in midgestation human fetal lung (HFL) is dramatically induced by cyclic AMP (cAMP). cAMP induction of SP-A expression is repressed by transforming growth factor β (TGF-β) and by hypoxia. In this study, we found that expression of the microRNA 29 (miR-29) family was significantly upregulated in epithelial cells isolated from mouse fetal lung during late gestation and in epithelial cells isolated from HFL explants during type II cell differentiation in culture...
August 15, 2016: Molecular and Cellular Biology
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