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Lin28A

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https://www.readbyqxmd.com/read/28592444/cellular-differentiation-state-modulates-the-mrna-export-activity-of-sr-proteins
#1
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...
June 7, 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
#2
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
#3
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...
June 3, 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
#4
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...
May 31, 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
#5
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
#6
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 to 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...
May 26, 2017: Diabetes
https://www.readbyqxmd.com/read/28525643/synthetic-mrna-devices-that-detect-endogenous-proteins-and-distinguish-mammalian-cells
#7
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...
May 19, 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
#8
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
#9
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
https://www.readbyqxmd.com/read/28281692/ibuprofen-results-in-alterations-of-human-fetal-testis-development
#10
Millissia Ben Maamar, Laurianne Lesné, Kristin Hennig, Christèle Desdoits-Lethimonier, Karen R Kilcoyne, Isabelle Coiffec, Antoine D Rolland, Cécile Chevrier, David M Kristensen, Vincent Lavoué, Jean-Philippe Antignac, Bruno Le Bizec, Nathalie Dejucq-Rainsford, Rod T Mitchell, Séverine Mazaud-Guittot, Bernard Jégou
Among pregnant women ibuprofen is one of the most frequently used pharmaceutical compounds with up to 28% reporting use. Regardless of this, it remains unknown whether ibuprofen could act as an endocrine disruptor as reported for fellow analgesics paracetamol and aspirin. To investigate this, we exposed human fetal testes (7-17 gestational weeks (GW)) to ibuprofen using ex vivo culture and xenograft systems. Ibuprofen suppressed testosterone and Leydig cell hormone INSL3 during culture of 8-9 GW fetal testes with concomitant reduction in expression of the steroidogenic enzymes CYP11A1, CYP17A1 and HSD17B3, and of INSL3...
March 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28179426/extracellular-signal-regulated-kinases-erks-phosphorylate-lin28a-protein-to-modulate-p19-cell-proliferation-and-differentiation
#11
Xiangyuan Liu, Min Chen, Long Li, Liyan Gong, Hu Zhou, Daming Gao
Lin28a, originally discovered in the nematode Caenorhabditis elegans and highly conserved across species, is a well characterized regulator of let-7 microRNA (miRNA) and is implicated in cell proliferation and pluripotency control. However, little is known about how Lin28a function is modulated at the post-translational level and thereby responds to major signaling pathways. Here we show that Lin28a is directly phosphorylated by ERK1/2 kinases at Ser-200. By editing lin28a gene with the CRISPR/Cas9-based method, we generated P19 mouse embryonic carcinoma stem cells expressing Lin28a-S200A (phospho-deficient) and Lin28a-S200D (phospho-mimetic) mutants, respectively, to study the functional impact of Ser-200 phosphorylation...
March 10, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28132840/a-rapid-induction-mechanism-for-lin28a-in-trophic-responses
#12
Alexandra M Amen, Claudia R Ruiz-Garzon, Jay Shi, Megha Subramanian, Daniel L Pham, Mollie K Meffert
Environmental cues provoke rapid transitions in gene expression to support growth and cellular plasticity through incompletely understood mechanisms. Lin28 RNA-binding proteins have evolutionarily conserved roles in post-transcriptional coordination of pro-growth gene expression, but signaling pathways allowing trophic stimuli to induce Lin28 have remained uncharacterized. We find that Lin28a protein exhibits rapid basal turnover in neurons and that mitogen-activated protein kinase (MAPK)-dependent phosphorylation of the RNA-silencing factor HIV TAR-RNA-binding protein (TRBP) promotes binding and stabilization of Lin28a, but not Lin28b, with an accompanying reduction in Lin28-regulated miRNAs, downstream of brain-derived neurotrophic factor (BDNF)...
February 2, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28049690/rewiring-of-embryonic-glucose-metabolism-via-suppression-of-pfk-1-and-aldolase-during-mouse-chorioallantoic-branching
#13
Hidenobu Miyazawa, Yoshifumi Yamaguchi, Yuki Sugiura, Kurara Honda, Koki Kondo, Fumio Matsuda, Takehiro Yamamoto, Makoto Suematsu, Masayuki Miura
Adapting the energy metabolism state to changing bioenergetic demands is essential for mammalian development accompanying massive cell proliferation and cell differentiation. However, it remains unclear how developing embryos meet the changing bioenergetic demands during the chorioallantoic branching (CB) stage, when the maternal-fetal exchange of gases and nutrients is promoted. In this study, using metabolome analysis with mass-labeled glucose, we found that developing embryos redirected glucose carbon flow into the pentose phosphate pathway via suppression of the key glycolytic enzymes PFK-1 and aldolase during CB...
January 1, 2017: Development
https://www.readbyqxmd.com/read/27992407/lin28-phosphorylation-by-mapk-erk-couples-signalling-to-the-post-transcriptional-control-of%C3%A2-pluripotency
#14
Kaloyan M Tsanov, Daniel S Pearson, Zhaoting Wu, Areum Han, Robinson Triboulet, Marc T Seligson, John T Powers, Jihan K Osborne, Susan Kane, Steven P Gygi, Richard I Gregory, George Q Daley
Signalling and post-transcriptional gene control are both critical for the regulation of pluripotency, yet how they are integrated to influence cell identity remains poorly understood. LIN28 (also known as LIN28A), a highly conserved RNA-binding protein, has emerged as a central post-transcriptional regulator of cell fate through blockade of let-7 microRNA biogenesis and direct modulation of mRNA translation. Here we show that LIN28 is phosphorylated by MAPK/ERK in pluripotent stem cells, which increases its levels via post-translational stabilization...
January 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/27941834/lin28a-promotes-self-renewal-and-proliferation-of-dairy-goat-spermatogonial-stem-cells-sscs-through-regulation-of-mtor-and-pi3k-akt
#15
Fanglin Ma, Zhe Zhou, Na Li, Liming Zheng, Chongyang Wu, Bowen Niu, Furong Tang, Xin He, Guangpeng Li, Jinlian Hua
Lin28a is a conserved RNA-binding protein that plays an important role in development, pluripotency, stemness maintenance, proliferation and self-renewal. Early studies showed that Lin28a serves as a marker of spermatogonial stem cells (SSCs) and promotes the proliferation capacity of mouse SSCs. However, there is little information about Lin28a in livestock SSCs. In this study, we cloned Capra hircus Lin28a CDS and found that it is evolutionarily conserved. Lin28a is widely expressed in different tissues of Capra hircus, but is expressed at a high level in the testis...
December 12, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27934604/generation-of-induced-pluripotent-stem-cells-ipscs-stably-expressing-crispr-based-synergistic-activation-mediator-sam
#16
Kai Xiong, Yan Zhou, Poul Hyttel, Lars Bolund, Kristine Karla Freude, Yonglun Luo
Human fibroblasts were engineered to express the CRISPR-based synergistic activation mediator (SAM) complex: dCas9-VP64 and MS2-P65-HSF1. Two induced pluripotent stem cells (iPSCs) clones expressing SAM were established by transducing these fibroblasts with lentivirus expressing OCT4, SOX2, KLF4 and C-MYC. We have validated that the reprogramming cassette is silenced in the SAM iPSC clones. Expression of pluripotency genes (OCT4, SOX2, LIN28A, NANOG, GDF3, SSEA4, and TRA-1-60), differentiation potential to all three germ layers, and normal karyotypes are validated...
November 17, 2016: Stem Cell Research
https://www.readbyqxmd.com/read/27906131/the-mir-125-family-is-an-important-regulator-of-the-expression-and-maintenance-of-maternal-effect-genes-during-preimplantational-embryo-development
#17
Kyeoung-Hwa Kim, You-Mi Seo, Eun-Young Kim, Su-Yeon Lee, Jini Kwon, Jung-Jae Ko, Kyung-Ah Lee
Previously, we reported that Sebox is a new maternal effect gene (MEG) that is required for early embryo development beyond the two-cell (2C) stage because this gene orchestrates the expression of important genes for zygotic genome activation (ZGA). However, regulators of Sebox expression remain unknown. Therefore, the objectives of the present study were to use bioinformatics tools to identify such regulatory microRNAs (miRNAs) and to determine the effects of the identified miRNAs on Sebox expression. Using computational algorithms, we identified a motif within the 3'UTR of Sebox mRNA that is specific to the seed region of the miR-125 family, which includes miR-125a-5p, miR-125b-5p and miR-351-5p...
November 2016: Open Biology
https://www.readbyqxmd.com/read/27881476/lin28a-uses-distinct-mechanisms-of-binding-to-rna-and-affects-mirna-levels-positively-and-negatively
#18
Jakub Stanislaw Nowak, Fruzsina Hobor, Angela Downie Ruiz Velasco, Nila Roy Choudhury, Gregory Heikel, Alastair Kerr, Andres Ramos, Gracjan Michlewski
Lin28a inhibits the biogenesis of let-7 miRNAs by triggering the polyuridylation and degradation of their precursors by terminal uridylyltransferases TUT4/7 and 3'-5' exoribonuclease Dis3l2, respectively. Previously, we showed that Lin28a also controls the production of neuro-specific miRNA-9 via a polyuridylation-independent mechanism. Here we reveal that the sequences and structural characteristics of pre-let-7 and pre-miRNA-9 are eliciting two distinct modes of binding to Lin28a. We present evidence that Dis3l2 controls miRNA-9 production...
March 2017: RNA
https://www.readbyqxmd.com/read/27859935/single-nucleotide-polymorphisms-within-micrornas-microrna-targets-and-microrna-biogenesis-genes-and-their-impact-on-colorectal-cancer-survival
#19
Lila E Mullany, Jennifer S Herrick, Roger K Wolff, Martha L Slattery
We have shown that single nucleotide polymorphisms (SNPs) in microRNA (miRNA) genes, miRNA target genes, and miRNA biogenesis genes minimally contribute to colon cancer risk. It is possible that these SNPs alter survival. We analyzed 565 SNPs in or adjacent to microRNAs, target genes, or biogenesis genes, using 1,115 cases and 1,173 controls; 837 cases had survival information. We tested SNPs for associations with colorectal cancer (CRC) survival using a Cox proportional hazard model adjusting for age, study center, gender, AJCC disease stage, and MSI tumor status...
April 2017: Genes, Chromosomes & Cancer
https://www.readbyqxmd.com/read/27793004/comparison-of-the-expression-and-function-of-lin28a-and-lin28b-in-colon-cancer
#20
Tianzhen Wang, Yan He, Yuanyuan Zhu, Mingwei Chen, Mingjiao Weng, Chao Yang, Yan Zhang, Ning Ning, Ran Zhao, Weiwei Yang, Yinji Jin, Jing Li, Riju James Rajkumar Ezakiel Redpath, Lei Zhang, Xiaoming Jin, Zhaohua Zhong, Fengmin Zhang, Yunwei Wei, Guomin Shen, Dong Wang, Ying Liu, Guangyu Wang, Xiaobo Li
Lin28A and Lin28B are highly conserved RNA binding proteins with similar structure and functions. Recent studies demonstrated that both of them act as oncogenes and promote cancer progression. However, few researches compared the expression and functions of both oncogenes in human malignant tumors at same time. Additionally, although the expression and role of Lin28B in colon cancer is frequently reported, the expression and functions of Lin28A in colon cancer are largely unknown. In this study, we have systematically evaluated the expressional pattern, mutation status and correlation of both Lin28A and Lin28B in colon cancer tissues for the first time, and compared the roles of Lin28A and Lin28B in the proliferation, migration, invasion and apoptosis of colon cancer cells in vitro...
November 29, 2016: Oncotarget
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