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Si Li, Hai-Yan Zhang, Zhen-Xian Du, Chao Li, Ming-Xin An, Zhi-Hong Zong, Bao-Qin Liu, Hua-Qin Wang
Beclin 1 has emerged as a haploinsufficient tumor suppression gene in a variety of human carcinomas. In order to clarify the role of Beclin 1 in thyroid cancer, Beclin 1 was knockdown in thyroid cancer cell lines. The current study demonstrated that knockdown of Beclin 1 resulted in morphological and molecular changes of thyroid cancer cells consistent with epithelial-mesenchymal transition (EMT), a morphogenetic procedure during which cells lose their epithelial characteristics and acquire mesenchymal properties concomitantly with gene expression reprogramming...
September 23, 2016: Oncotarget
Elizabeth J F White, Aerielle E Matsangos, Gerald M Wilson
AUF1 is a family of four RNA-binding proteins (RBPs) generated by alternative pre-messenger RNA (pre-mRNA) splicing, with canonical roles in controlling the stability and/or translation of mRNA targets based on recognition of AU-rich sequences within mRNA 3' untranslated regions. However, recent studies identifying AUF1 target sites across the transcriptome have revealed that these canonical functions are but a subset of its roles in posttranscriptional regulation of gene expression. In this review, we describe recent developments in our understanding of the RNA-binding properties of AUF1 together with their biochemical implications and roles in directing mRNA decay and translation...
September 13, 2016: Wiley Interdisciplinary Reviews. RNA
Huda H Al-Khalaf, Abdelilah Aboussekhra
Senescence and epithelial-to-mesenchymal transition (EMT) processes are under the control of common tumor suppressor proteins, EMT transcription factors, and microRNAs. However, the molecular mechanisms that coordinate the functional link between senescence and EMT are still elusive. We have shown here that p16(INK4A) -reltaed induction of senescence is mediated through miR-141 and miR-146b-5p. These 2 microRNAs are up-regulated in aging human fibroblast and epithelial cells. Furthermore, miR-141 and miR146b-5p trigger cell cycle arrest at G1 phase and induce senescence in primary human fibroblasts and breast cancer cells in the presence and absence of p16(INK4A) ...
September 6, 2016: Molecular Carcinogenesis
Jiahui Chen, Lihui Liu, Guifeng Wei, Wei Wu, Huaxia Luo, Jiao Yuan, Jianjun Luo, Runsheng Chen
The identification and characterization of long non-coding RNAs (lncRNAs) in diverse biological processes has recently developed rapidly. The large amounts of non-coding RNAs scale consistent with developmental complexity in eukaryotes, indicating that most of these transcripts may have functions in the regulation of biological processes and disorder in the organisms. In particular, Understanding of the overall biological significance of lncRNAs in cancers still remains limited. Here, we found a nuclear-retained lncRNA, termed Lnc_ASNR (apoptosis suppressing-noncoding RNA), which serves as a repressor of apoptosis...
2016: Scientific Reports
Zdenka Navratilova, Eva Novosadova, Michael Hagemann-Jensen, Susanna Kullberg, Vitezslav Kolek, Johan Grunewald, Martin Petrek
BACKGROUND: Sarcoidosis is characterised by up-regulation of cytokines and chemokine ligands/receptors and proteolytic enzymes. This pro-inflammatory profile is regulated post-transcriptionally by RNA-binding proteins (RBPs). We investigated in vivo expression of six RBPs (AUF1, HuR, NCL, TIA, TIAR, PCBP2) and two inhibitors of proteolytic enzymes (RECK, PTEN) in pulmonary sarcoidosis and compared it to the expression in four control groups of healthy individuals and patients with other respiratory diseases: chronic obstructive pulmonary disease (COPD), asthma and idiopathic interstitial pneumonias (IIPs)...
2016: PloS One
Susann Friedrich, Tobias Schmidt, Angelika Schierhorn, Hauke Lilie, Grit Szczepankiewicz, Sandra Bergs, Uwe G Liebert, Ralph P Golbik, Sven-Erik Behrens
A prerequisite for the intracellular replication process of the Flavivirus West Nile virus (WNV) is the cyclization of the viral RNA genome, which enables the viral replicase to initiate RNA synthesis. Our earlier studies indicated that the p45 isoform of the cellular AU-rich element binding protein 1 (AUF1) has an RNA chaperone activity, which supports RNA cyclization and viral RNA synthesis by destabilizing a stem structure at the WNV RNA's 3'-end. Here we show that in mammalian cells, AUF1 p45 is consistently modified by arginine methylation of its C terminus...
October 2016: RNA
Devon M Chenette, Adam B Cadwallader, Tiffany L Antwine, Lauren C Larkin, Jinhua Wang, Bradley B Olwin, Robert J Schneider
Following skeletal muscle injury, muscle stem cells (satellite cells) are activated, proliferate, and differentiate to form myofibers. We show that mRNA-decay protein AUF1 regulates satellite cell function through targeted degradation of specific mRNAs containing 3' AU-rich elements (AREs). auf1(-/-) mice undergo accelerated skeletal muscle wasting with age and impaired skeletal muscle repair following injury. Satellite cell mRNA analysis and regeneration studies demonstrate that auf1(-/-) satellite cell self-renewal is impaired due to increased stability and overexpression of ARE-mRNAs, including cell-autonomous overexpression of matrix metalloprotease MMP9...
August 2, 2016: Cell Reports
Young Jun Choi, Je-Hyun Yoon, Jeong Ho Chang
AU-rich element binding/degradation factor 1 (AUF1) plays a role in destabilizing mRNAs by forming complexes with AU-rich elements (ARE) in the 3'-untranslated regions. Multiple AUF1-ARE complexes regulate the translation of encoded products related to the cell cycle, apoptosis, and inflammation. AUF1 contains two tandem RNA recognition motifs (RRM) and a Gln- (Q-) rich domain in their C-terminal region. To observe how the two RRMs are involved in recognizing ARE, we obtained the AUF1-p37 protein covering the two RRMs...
2016: BioMed Research International
Siti-Fauziah Hendrayani, Bothaina Al-Harbi, Mysoon M Al-Ansari, Gabriela Silva, Abdelilah Aboussekhra
The IL-6/STAT3/NF-κB positive feedback loop links inflammation to cancer and maintains cells at a transformed state. Similarly, cancer-associated myofibroblats remains active even in absence of cancer cells. However, the molecular basis of this sustained active state remains elusive. We have shown here that breast cancer cells and IL-6 persistently activate breast stromal fibroblasts through the stimulation of the positive IL-6/STAT3/NF-κB feedback loop. Transient neutralization of IL-6 in culture inhibited this signaling circuit and reverted myofibrobalsts to a normalized state, suggesting the implication of the IL-6 autocrine feedback loop as well...
May 26, 2016: Oncotarget
Nicole Noren Hooten, Alejandro Martin-Montalvo, Douglas F Dluzen, Yongqing Zhang, Michel Bernier, Alan B Zonderman, Kevin G Becker, Myriam Gorospe, Rafael de Cabo, Michele K Evans
Metformin, an oral hypoglycemic agent, has been used for decades to treat type 2 diabetes mellitus. Recent studies indicate that mice treated with metformin live longer and have fewer manifestations of age-related chronic disease. However, the molecular mechanisms underlying this phenotype are unknown. Here, we show that metformin treatment increases the levels of the microRNA-processing protein DICER1 in mice and in humans with diabetes mellitus. Our results indicate that metformin upregulates DICER1 through a post-transcriptional mechanism involving the RNA-binding protein AUF1...
June 2016: Aging Cell
B Trojanowicz, C Sekulla, H Dralle, C Hoang-Vu
Both adenylate-uridylate rich elements binding proteins AUF1 and HuR may participate in thyroid carcinoma progression. In this study we investigated the expression of both factors on a protein level with a special focus on follicular adenoma and follicular thyroid carcinoma. By employment of immunofluorescence and western blot on 68 thyroid tissues including 7 goiter, 16 follicular adenoma (4 adenomatous hyperplasia), 19 follicular thyroid carcinomas, 13 papillary thyroid carcinomas and 14 undifferentiated thyroid carcinomas we investigated protein expression of AUF1 and HuR...
2016: Neoplasma
Jianguo Huang, Ali Zhang, Tsui-Ting Ho, Ziqiang Zhang, Nanjiang Zhou, Xianfeng Ding, Xu Zhang, Min Xu, Yin-Yuan Mo
Linc-RoR was originally identified to be a regulator for induced pluripotent stem cells in humans and it has also been implicated in tumorigenesis. However, the underlying mechanism of Linc-RoR-mediated gene expression in cancer is poorly understood. The present study demonstrates that Linc-RoR plays an oncogenic role in part through regulation of c-Myc expression. Linc-RoR knockout (KO) suppresses cell proliferation and tumor growth. In particular, Linc-RoR KO causes a significant decrease in c-Myc whereas re-expression of Linc-RoR in the KO cells restores the level of c-Myc...
April 20, 2016: Nucleic Acids Research
Jing-Yi Lin, Gary Brewer, Mei-Ling Li
EV71 (enterovirus 71) RNA contains an internal ribosomal entry site (IRES) that directs cap-independent initiation of translation. IRES-dependent translation requires the host's translation initiation factors and IRES-associated trans-acting factors (ITAFs). We reported recently that mRNA decay factor AUF1 is a negative-acting ITAF that binds IRES stem-loop II. We also reported that the small RNA-processing enzyme Dicer produces at least four small RNAs (vsRNAs) from the EV71 IRES. One of these, vsRNA1, derived from IRES stem-loop II, reduces IRES activity and virus replication...
2015: PloS One
Kuei-Yang Hsiao, Meng-Hsing Wu, Ning Chang, Shang-Hsun Yang, Chun-Wei Wu, H Sunny Sun, Shaw-Jenq Tsai
STUDY HYPOTHESIS: DNA methylation is regulated by hypoxia in endometriosis. STUDY FINDING: Hypoxia causes global hypomethylation through AU-rich element binding factor 1 (AUF1)/microRNA-148a (miR-148a)-mediated destabilization of DNA methyltransferase 1 (DNMT1) mRNA. WHAT IS KNOWN ALREADY: Eutopic endometrial and ectopic endometriotic stromal cells have the same genetic background, but differ in several cellular and molecular responses. Both hypoxia and DNA methylation regulate several genes involved in the development of endometriosis...
December 2015: Molecular Human Reproduction
Yong-Seok Lee, Jin-A Lee, Bong-Kiun Kaang
Formation of long-term memories requires coordinated gene expression, which can be regulated at transcriptional, post-transcriptional, and translational levels. Post-transcriptional stabilization and destabilization of mRNAs provides precise temporal and spatial regulation of gene expression, which is critical for consolidation of synaptic plasticity and memory. mRNA stability is regulated by interactions between the cis-acting elements of mRNAs, such as adenine-uridine-rich elements (AREs), and the trans-acting elements, ARE-binding proteins (AUBPs)...
October 2015: Neurobiology of Learning and Memory
Je-Hyun Yoon, Myung Hyun Jo, Elizabeth J F White, Supriyo De, Markus Hafner, Beth E Zucconi, Kotb Abdelmohsen, Jennifer L Martindale, Xiaoling Yang, William H Wood, Yu Mi Shin, Ji-Joon Song, Thomas Tuschl, Kevin G Becker, Gerald M Wilson, Sungchul Hohng, Myriam Gorospe
Eukaryotic gene expression is tightly regulated post-transcriptionally by RNA-binding proteins (RBPs) and microRNAs. The RBP AU-rich-binding factor 1 (AUF1) isoform p37 was found to have high affinity for the microRNA let-7b in vitro (Kd = ∼ 6 nM) in cells. Ribonucleoprotein immunoprecipitation, in vitro association, and single-molecule-binding analyses revealed that AUF1 promoted let-7b loading onto Argonaute 2 (AGO2), the catalytic component of the RNA-induced silencing complex (RISC). In turn, AGO2-let-7 triggered target mRNA decay...
August 1, 2015: Genes & Development
Anastasios Fotinos, David T Fritz, Steven Lisica, Yijun Liu, Melissa B Rogers
The amount, timing, and location of bone morphogenetic protein 2 (BMP2) synthesis influences the differentiation of pluripotent mesenchymal cells in embryos and adults. The BMP2 3'untranslated region (3'UTR) contains a highly conserved AU-rich element (ARE) embedded in a sequence that commonly represses gene expression in mesenchymal cells. Computational analyses indicate that this site also may bind several microRNAs (miRNAs). Although miRNAs frequently target AU-rich regions, this ARE is unusual because the miRNAs directly span the ARE...
February 2016: Journal of Cellular Biochemistry
Genaro Pimienta, Victor Fok, Maria Haslip, Maria Nagy, Seyedtaghi Takyar, Joan A Steitz
In Epstein-Barr virus (EBV) latent infection, the EBV-encoded RNAs EBER1 and EBER2 accumulate in the host cell nucleus to ~10(6) copies. While the expression of EBERs in cell lines is associated with transformation, a mechanistic explanation of their roles in EBV latency remains elusive. To identify EBER-specific gene expression features, we compared the proteome and mRNA transcriptome from BJAB cells (an EBV-negative B lymphoma cell line) stably transfected with an empty plasmid or with one carrying both EBER genes...
2015: PloS One
Roopa Thapar
The peptidyl-prolyl cis-trans isomerases (PPIases) that include immunophilins (cyclophilins and FKBPs) and parvulins (Pin1, Par14, Par17) participate in cell signaling, transcription, pre-mRNA processing and mRNA decay. The human genome encodes 19 cyclophilins, 18 FKBPs and three parvulins. Immunophilins are receptors for the immunosuppressive drugs cyclosporin A, FK506, and rapamycin that are used in organ transplantation. Pin1 has also been targeted in the treatment of Alzheimer's disease, asthma, and a number of cancers...
2015: Biomolecules
Thomas Beiter, Miriam Hoene, Frauke Prenzler, Frank C Mooren, Jürgen M Steinacker, Cora Weigert, Andreas M Nieß, Barbara Munz
The role of inflammation in skeletal muscle adaptation to exercise is complex and has hardly been elucidated so far. While the acute inflammatory response to exercise seems to promote skeletal muscle training adaptation and regeneration, persistent, low-grade inflammation, as seen in a multitude of chronic diseases, is obviously detrimental. The regulation of cytokine production in skeletal muscle cells has been relatively well studied, yet little is known about the compensatory and anti-inflammatory mechanisms that resolve inflammation and restore tissue homeostasis...
2015: Exercise Immunology Review
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