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Lin28A

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https://www.readbyqxmd.com/read/28938627/prostate-tumor-overexpressed-1-ptov1-promotes-docetaxel-resistance-and-survival-of-castration-resistant-prostate-cancer-cells
#1
Verónica Cánovas, Yolanda Puñal, Valentina Maggio, Enric Redondo, Mercedes Marín, Begoña Mellado, Mireia Olivan, Matilde Lleonart, Jacques Planas, Juan Morote, Rosanna Paciucci
Metastatic prostate cancer is presently incurable. The oncogenic protein PTOV1, first described in prostate cancer, was reported as overexpressed and significantly correlated with poor survival in numerous tumors. Here, we investigated the role of PTOV1 in prostate cancer survival to docetaxel and self-renewal ability. Transduction of PTOV1 in docetaxel-sensitive Du145 and PC3 cells significantly increased cell survival after docetaxel exposure and induced docetaxel-resistance genes expression (ABCB1, CCNG2 and TUBB2B)...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28921745/transcription-factor-ccaat-enhancer-binding-protein-%C3%AE-upregulates-microrna-let-7f-1-in-human-endocervical-cells
#2
Kanchana Ayyar, Kudumula Venkata Rami Reddy
PROBLEM: In endocervical epithelial cells (End1/E6E7), miRNA let-7f plays an important role in the control of innate immunity. The underlying molecular mechanism for let-7f regulation in these cells remains largely unclear. METHODS OF STUDY: let-7f was knocked down in End1/E6E7 cells using siRNA, and differential gene expression was analyzed by microarray. Differentially expressed genes were validated by qPCR and Western blot. Expression of let-7f was studied by qPCR after inhibition of C/EBPβ with betulinic acid (BA) and pCMVβ plasmid and after overexpression of C/EBPβ with pCMVβ+ plasmid...
September 16, 2017: American Journal of Reproductive Immunology: AJRI
https://www.readbyqxmd.com/read/28892074/replacing-reprogramming-factors-with-antibodies-selected-from-combinatorial-antibody-libraries
#3
Joel W Blanchard, Jia Xie, Nadja El-Mecharrafie, Simon Gross, Sohyon Lee, Richard A Lerner, Kristin K Baldwin
The reprogramming of differentiated cells into induced pluripotent stem cells (iPSCs) is usually achieved by exogenous induction of transcription by factors acting in the nucleus. In contrast, during development, signaling pathways initiated at the membrane induce differentiation. The central idea of this study is to identify antibodies that can catalyze cellular de-differentiation and nuclear reprogramming by acting at the cell surface. We screen a lentiviral library encoding ∼100 million secreted and membrane-bound single-chain antibodies and identify antibodies that can replace either Sox2 and Myc (c-Myc) or Oct4 during reprogramming of mouse embryonic fibroblasts into iPSCs...
September 11, 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/28892064/a-mouse-model-for-embryonal-tumors-with-multilayered-rosettes-uncovers-the-therapeutic-potential-of-sonic-hedgehog-inhibitors
#4
Julia E Neumann, Annika K Wefers, Sander Lambo, Edoardo Bianchi, Marie Bockstaller, Mario M Dorostkar, Valerie Meister, Pia Schindler, Andrey Korshunov, Katja von Hoff, Johannes Nowak, Monika Warmuth-Metz, Marlon R Schneider, Ingrid Renner-Müller, Daniel J Merk, Mehdi Shakarami, Tanvi Sharma, Lukas Chavez, Rainer Glass, Jennifer A Chan, M Mark Taketo, Philipp Neumann, Marcel Kool, Ulrich Schüller
Embryonal tumors with multilayered rosettes (ETMRs) have recently been described as a new entity of rare pediatric brain tumors with a fatal outcome. We show here that ETMRs are characterized by a parallel activation of Shh and Wnt signaling. Co-activation of these pathways in mouse neural precursors is sufficient to induce ETMR-like tumors in vivo that resemble their human counterparts on the basis of histology and global gene-expression analyses, and that point to apical radial glia cells as the possible tumor cell of origin...
September 11, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28820723/a-lncrna-fine-tunes-the-dynamics-of-a-cell-state-transition-involving-lin28-let-7-and-de-novo-dna-methylation
#5
Meng Amy Li, Paulo P Amaral, Priscilla Cheung, Jan H Bergmann, Masaki Kinoshita, Tüzer Kalkan, Meryem Ralser, Sam Robson, Ferdinand von Meyenn, Maike Paramor, Fengtang Yang, Caifu Chen, Jennifer Nichols, David L Spector, Tony Kouzarides, Lin He, Austin Smith
Execution of pluripotency requires progression from the naïve status represented by mouse embryonic stem cells (ESCs) to a state capacitated for lineage specification. This transition is coordinated at multiple levels. Non-coding RNAs may contribute to this regulatory orchestra. We identified a rodent-specific long non-coding RNA (lncRNA) linc1281, hereafter Ephemeron (Eprn), that modulates the dynamics of exit from naïve pluripotency. Eprn deletion delays the extinction of ESC identity, an effect associated with perduring Nanog expression...
August 18, 2017: ELife
https://www.readbyqxmd.com/read/28771809/role-of-xist-mir-29a-lin28a-pathway-in-denatured-dermis-and-human-skin-fibroblasts-hsfs-after-thermal-injury
#6
Le Guo, Xu Huang, Pengfei Liang, Pihong Zhang, Minghua Zhang, Licheng Ren, Jizhang Zeng, Xv Cui, Xiaoyuan Huang
Denatured dermis is a part of the dermis in deep burn wound and has the ability to restore normal morphology and function. In our previous study, we revealed that miR-29a downregulation in denatured dermis may help burn wound healing in the later phase, and further enhance type I collagen synthesis. LIN28A, a highly-conserved RNA binding protein expressed during embryogenesis, plays roles in development, pluripotency, metabolism, as well as tissue repair in adults. In the present study, we investigated the functional roles of LIN28A in human skin fibroblasts (HSFs) and extracellular matrix (ECM), and the interaction between miR-29a and LIN28A...
August 3, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28750082/enhanced-generation-of-ipscs-from-older-adult-human-cells-by-a-synthetic-five-factor-self-replicative-rna
#7
Naohisa Yoshioka, Steven F Dowdy
We previously devised a polycistronic, synthetic self-replicating RNA (srRNA) to generate human induced Pluripotent Stem Cells (iPSCs) that simultaneously expresses four reprogramming factors (4F). However, while the best 4F srRNA efficiently generated iPSCs from young fibroblasts, it was inefficient on adult human fibroblasts (>50 years). To increase the iPSC generation efficiency, we included additional reprogramming factors. We found that a single transfection of a five factor (5F) srRNA, containing OCT4, KLF4, SOX2, GLIS1 and c-MYC, robustly generated iPSCs from adult human fibroblasts aged 54 to 77 and from a 24 year old cardiomyopathy patient donor...
2017: PloS One
https://www.readbyqxmd.com/read/28746394/effects-of-oxidative-and-thermal-stresses-on-stress-granule-formation-in-human-induced-pluripotent-stem-cells
#8
Freshteh Palangi, Samson M Samuel, I Richard Thompson, Chris R Triggle, Mohamed M Emara
Stress Granules (SGs) are dynamic ribonucleoprotein aggregates, which have been observed in cells subjected to environmental stresses, such as oxidative stress and heat shock (HS). Although pluripotent stem cells (PSCs) are highly sensitive to oxidative stress, the role of SGs in regulating PSC self-renewal and differentiation has not been fully elucidated. Here we found that sodium arsenite (SA) and HS, but not hydrogen peroxide (H2O2), induce SG formation in human induced (hi) PSCs. Particularly, we found that these granules contain the well-known SG proteins (G3BP, TIAR, eIF4E, eIF4A, eIF3B, eIF4G, and PABP), were found in juxtaposition to processing bodies (PBs), and were disassembled after the removal of the stress...
2017: PloS One
https://www.readbyqxmd.com/read/28744687/lin28a-a-sensitive-immunohistochemical-marker-for-embryonal-tumor-with-multilayered-rosettes-etmr-is-also-positive-in-a-subset-of-atypical-teratoid-rhabdoid-tumor-at-rt
#9
Shilpa Rao, R T Rajeswarie, T Chickabasaviah Yasha, Bevinahalli N Nandeesh, Arimappamagan Arivazhagan, Vani Santosh
INTRODUCTION: CNS embryonal tumors comprise a group of highly malignant neoplasms with a wide spectrum of histomorphological entities that includes Medulloblastoma (MB), Atypical Teratoid/Rhabdoid Tumor (AT/RT), Neuroblastoma (NB), Ganglioneuroblastoma (GNB), Embryonal Tumor with Multilayered Rosettes (ETMR), and the embryonal tumor-Not Otherwise Specified (NOS). The entity ETMR includes previously described histopathologic patterns-Embryonal Tumor with Abundant Neuropil and True Rosettes (ETANTR), Ependymoblastoma (EBL), and Medulloepithelioma (MEPL)...
July 25, 2017: Child's Nervous System: ChNS: Official Journal of the International Society for Pediatric Neurosurgery
https://www.readbyqxmd.com/read/28710541/injury-induced-purinergic-signalling-molecules-upregulate-pluripotency-gene-expression-and-mitotic-activity-of-progenitor-cells-in-the-zebrafish-retina
#10
Matías P Medrano, Claudio A Bejarano, Ariadna G Battista, Graciela D Venera, Ramón O Bernabeu, Maria Paula Faillace
Damage in fish activates retina repair that restores sight. The purinergic signalling system serves multiple homeostatic functions and has been implicated in cell cycle control of progenitor cells in the developing retina. We examined whether changes in the expression of purinergic molecules were instrumental in the proliferative phase after injury of adult zebrafish retinas with ouabain. P2RY1 messenger RNA (mRNA) increased early after injury and showed maximal levels at the time of peak progenitor cell proliferation...
July 14, 2017: Purinergic Signalling
https://www.readbyqxmd.com/read/28647433/targeted-release-of-transcription-factors-for-human-cell-reprogramming-by-zebra-cell-penetrating-peptide
#11
Benjamin Caulier, Lionel Berthoin, Helène Coradin, Frédéric Garban, Marie Claire Dagher, Benoît Polack, Bertrand Toussaint, Jean Luc Lenormand, David Laurin
Transcription factors (TFs) are key actors of the control of gene expression and consequently of every major process within cells, ranging from cell fate determination, cell cycle control and response to environment. Their ectopic expression has proven high potential in reprogramming cells for regenerative medicine; ontogenesis studies and cell based modelling. Direct delivery of proteins could represent an alternative to current reprogramming methods using gene transfer but still needs technological improvements...
June 21, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28592444/cellular-differentiation-state-modulates-the-mrna-export-activity-of-sr-proteins
#12
COMPARATIVE STUDY
Valentina Botti, François McNicoll, Michaela C Steiner, Florian M Richter, Anfisa Solovyeva, Marius Wegener, Oliver D Schwich, Ina Poser, Kathi Zarnack, Ilka Wittig, Karla M Neugebauer, Michaela Müller-McNicoll
SR proteins function in nuclear pre-mRNA processing, mRNA export, and translation. To investigate their cellular dynamics, we developed a quantitative assay, which detects differences in nucleocytoplasmic shuttling among seven canonical SR protein family members. As expected, SRSF2 and SRSF5 shuttle poorly in HeLa cells but surprisingly display considerable shuttling in pluripotent murine P19 cells. Combining individual-resolution cross-linking and immunoprecipitation (iCLIP) and mass spectrometry, we show that elevated arginine methylation of SRSF5 and lower phosphorylation levels of cobound SRSF2 enhance shuttling of SRSF5 in P19 cells by modulating protein-protein and protein-RNA interactions...
July 3, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28587210/curcumin-inhibits-lin-28a-through-the-activation-of-mirna-98-in-the-lung-cancer-cell-line-a549
#13
Wei-Lun Liu, Jia-Ming Chang, Inn-Wen Chong, Yi-Li Hung, Yung-Hsiang Chen, Wen-Tsung Huang, Hsuan-Fu Kuo, Chong-Chao Hsieh, Po-Len Liu
Metastasis is common in lung cancer and is associated with poor clinical outcomes and increased mortality. Curcumin is a natural anti-cancer agent that inhibits the metastasis of various cancers by modulating the expression of micro (mi) RNAs such as miR-98, which acts as a tumor suppressor. This study investigated the effect of curcumin on miR-98 expression and in vitro cell line growth and invasiveness in lung cancer. Curcumin treatment enhanced the expression of miR-98 and reduced that of the miR-98 target gene LIN28A as well as matrix metalloproteinase (MMP) 2 and MMP9 in vitro and in vivo...
June 3, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28582547/the-torc1-2-inhibitor-tak228-sensitizes-atypical-teratoid-rhabdoid-tumors-to-cisplatin-induced-cytotoxicity
#14
Jeffrey A Rubens, Sabrina Z Wang, Antoinette Price, Melanie F Weingart, Sariah J Allen, Brent A Orr, Charles G Eberhart, Eric H Raabe
Background: Atypical teratoid/rhabdoid tumors (AT/RTs) are deadly pediatric brain tumors driven by LIN28. Mammalian target of rapamycin (mTOR) is activated in many deadly, drug-resistant cancers and governs important cellular functions such as metabolism and survival. LIN28 regulates mTOR in normal cells. We therefore hypothesized that mTOR is activated downstream of LIN28 in AT/RT, and the brain-penetrating mTOR complex 1 and 2 (mTORC1/2) kinase inhibitor TAK228 would reduce AT/RT tumorigenicity...
October 1, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28577895/sox2-regulates-m%C3%A3-ller-glia-reprogramming-and-proliferation-in-the-regenerating-zebrafish-retina-via-lin28-and-ascl1a
#15
Ryne A Gorsuch, Manuela Lahne, Clare E Yarka, Michael E Petravick, Jingling Li, David R Hyde
Sox2 is a well-established neuronal stem cell-associated transcription factor that regulates neural development and adult neurogenesis in vertebrates, and is one of the critical genes used to reprogram differentiated cells into induced pluripotent stem cells. We examined if Sox2 was involved in the early reprogramming-like events that Müller glia undergo as they upregulate many pluripotency- and neural stem cell-associated genes required for proliferation in light-damaged adult zebrafish retinas. In the undamaged adult zebrafish retina, Sox2 is expressed in Müller glia and a subset of amacrine cells, similar to other vertebrates...
August 2017: Experimental Eye Research
https://www.readbyqxmd.com/read/28569789/knockdown-of-mir-128a-induces-lin28a-expression-and-reverts-myeloid-differentiation-blockage-in-acute-myeloid-leukemia
#16
Luciana De Luca, Stefania Trino, Ilaria Laurenzana, Daniela Tagliaferri, Geppino Falco, Vitina Grieco, Gabriella Bianchino, Filomena Nozza, Valentina Campia, Francesca D'Alessio, Francesco La Rocca, Antonella Caivano, Oreste Villani, Daniela Cilloni, Pellegrino Musto, Luigi Del Vecchio
Lin28A is a highly conserved RNA-binding protein that concurs to control the balance between stemness and differentiation in several tissue lineages. Here, we report the role of miR-128a/Lin28A axis in blocking cell differentiation in acute myeloid leukemia (AML), a genetically heterogeneous disease characterized by abnormally controlled proliferation of myeloid progenitor cells accompanied by partial or total inability to undergo terminal differentiation. First, we found Lin28A underexpressed in blast cells from AML patients and AML cell lines as compared with CD34+ normal precursors...
June 1, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28550108/hypothalamic-ventromedial-lin28a-enhances-glucose-metabolism-in-diet-induced-obesity
#17
Jung Dae Kim, Chitoku Toda, Cristina M Ramírez, Carlos Fernández-Hernando, Sabrina Diano
The Lin28a/Let-7 axis has been studied in peripheral tissues for its role in metabolism regulation. However, its central function remains unclear. Here we found that Lin28a is highly expressed in the hypothalamus compared with peripheral tissues. Its expression is positively correlated with positive energy balance, suggesting a potential central role for Lin28a in metabolism regulation. Thus, we targeted the hypothalamic ventromedial nucleus (VMH) to selectively overexpress (Lin28aKI(VMH) ) or downregulate (Lin28aKD(VMH) ) Lin28a expression in mice...
August 2017: Diabetes
https://www.readbyqxmd.com/read/28525643/synthetic-mrna-devices-that-detect-endogenous-proteins-and-distinguish-mammalian-cells
#18
Shunsuke Kawasaki, Yoshihiko Fujita, Takashi Nagaike, Kozo Tomita, Hirohide Saito
Synthetic biology has great potential for future therapeutic applications including autonomous cell programming through the detection of protein signals and the production of desired outputs. Synthetic RNA devices are promising for this purpose. However, the number of available devices is limited due to the difficulty in the detection of endogenous proteins within a cell. Here, we show a strategy to construct synthetic mRNA devices that detect endogenous proteins in living cells, control translation and distinguish cell types...
July 7, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28423547/genomic-imbalances-are-involved-in-mir-30c-and-let-7a-deregulation-in-ovarian-tumors-implications-for-hmga2-expression
#19
Antonio Agostini, Marta Brunetti, Ben Davidson, Claes G Tropé, Sverre Heim, Ioannis Panagopoulos, Francesca Micci
The High-mobility group AT-hook 2 protein (HMGA2) is involved in different processes during tumorigenesis. High expression levels of HMGA2 are found in various types of cancer, with recent studies highlighting the important role of miRNAs in the regulation of HMGA2 expression. We report a study of 155 ovarian tumors (30 sex-cord stromal tumors, 22 borderline tumors, and 103 carcinomas) analyzed for HMGA2 expression as well as the expression of two miRNAs targeting this gene, let-7a and miR-30c. We also evaluated the expression of the fragile histidine triad (FHIT) and lin28 homologues (LIN28A/B) genes which are known to be an enhancer of miR-30c expression and a repressor of let-7a, respectively...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28400788/the-lin28-let-7-pathway-in-cancer
#20
REVIEW
Julien Balzeau, Miriam R Menezes, Siyu Cao, John P Hagan
Among all tumor suppressor microRNAs, reduced let-7 expression occurs most frequently in cancer and typically correlates with poor prognosis. Activation of either LIN28A or LIN28B, two highly related RNA binding proteins (RBPs) and proto-oncogenes, is responsible for the global post-transcriptional downregulation of the let-7 microRNA family observed in many cancers. Specifically, LIN28A binds the terminal loop of precursor let-7 and recruits the Terminal Uridylyl Transferase (TUTase) ZCCHC11 that polyuridylates pre-let-7, thereby blocking microRNA biogenesis and tumor suppressor function...
2017: Frontiers in Genetics
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