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https://www.readbyqxmd.com/read/28301057/the-correlation-between-lin28b-gene-potentially-functional-variants-and-wilms-tumor-susceptibility-in-chinese-children
#1
Wen Fu, Guo-Chang Liu, Zhang Zhao, Jinhong Zhu, Wei Jia, Shi-Bo Zhu, Jin-Hua Hu, Feng-Hua Wang, Jing He, Huimin Xia
BACKGROUND: Wilms tumor (WT) is the most common urologic cancer in children. However, genetic bases underlying WT remain largely unknown. Previous studies indicated that Lin28 homolog B (LIN28B) level is significantly elevated in some WTs. Enforced expression of Lin28b during kidney development could induce WT. Genetic variations in the LIN28B gene may be related to WT susceptibility. METHOD: In this study, we aimed to assess the association between LIN28B gene polymorphisms and WT susceptibility in Chinese children...
March 16, 2017: Journal of Clinical Laboratory Analysis
https://www.readbyqxmd.com/read/28297670/lin28-zinc-knuckle-domain-is-required-and-sufficient-to-induce-let-7-oligouridylation
#2
Longfei Wang, Yunsun Nam, Anna K Lee, Chunxiao Yu, Kira Roth, Casandra Chen, Elizabeth M Ransey, Piotr Sliz
LIN28 is an RNA binding protein that plays crucial roles in pluripotency, glucose metabolism, tissue regeneration, and tumorigenesis. LIN28 binds to the let-7 primary and precursor microRNAs through bipartite recognition and induces degradation of let-7 precursors (pre-let-7) by promoting oligouridylation by terminal uridylyltransferases (TUTases). Here, we report that the zinc knuckle domain (ZKD) of mouse LIN28 recruits TUT4 to initiate the oligouridylation of let-7 precursors. Our crystal structure of human LIN28 in complex with a fragment of pre-let-7f-1 determined to 2...
March 14, 2017: Cell Reports
https://www.readbyqxmd.com/read/28147339/oncogenic-mechanisms-of-lin28-in-breast-cancer-new-functions-and-therapeutic-opportunities
#3
REVIEW
Hanchu Xiong, Wenhe Zhao, Ji Wang, Benjamin J Seifer, Chenyang Ye, Yongxia Chen, Yunlu Jia, Cong Chen, Jianguo Shen, Linbo Wang, Xinbing Sui, Jichun Zhou
The RNA binding protein Lin28 is best known for the critical role in cell development, recent researches also have implied its oncogenic function in various human cancers, including breast cancer. Specifically, aberrant Lin28 participates in multiple pathological processes, such as proliferation, metastasis, radiotherapy and chemotherapy resistance, metabolism, immunity and inflammation as well as stemness. In this review, we summarize the let-7-dependent and let-7-independent mechanism regulated by Lin28, focusing on its relation with tumor hallmarks in breast cancer, and subsequently discuss our present knowledge of Lin28 to develop a molecular-based therapeutic strategy against breast cancer...
January 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28132840/a-rapid-induction-mechanism-for-lin28a-in-trophic-responses
#4
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/28128346/a-lin28-homologue-reprograms-differentiated-cells-to-stem-cells-in-the-moss-physcomitrella-patens
#5
Chen Li, Yusuke Sako, Akihiro Imai, Tomoaki Nishiyama, Kari Thompson, Minoru Kubo, Yuji Hiwatashi, Yukiko Kabeya, Dale Karlson, Shu-Hsing Wu, Masaki Ishikawa, Takashi Murata, Philip N Benfey, Yoshikatsu Sato, Yosuke Tamada, Mitsuyasu Hasebe
Both land plants and metazoa have the capacity to reprogram differentiated cells to stem cells. Here we show that the moss Physcomitrella patens Cold-Shock Domain Protein 1 (PpCSP1) regulates reprogramming of differentiated leaf cells to chloronema apical stem cells and shares conserved domains with the induced pluripotent stem cell factor Lin28 in mammals. PpCSP1 accumulates in the reprogramming cells and is maintained throughout the reprogramming process and in the resultant stem cells. Expression of PpCSP1 is negatively regulated by its 3'-untranslated region (3'-UTR)...
January 27, 2017: Nature Communications
https://www.readbyqxmd.com/read/28102845/h19-let-7-lin28-reciprocal-negative-regulatory-circuit-promotes-breast-cancer-stem-cell-maintenance
#6
Fei Peng, Ting-Ting Li, Kai-Li Wang, Guo-Qing Xiao, Ju-Hong Wang, Hai-Dong Zhao, Zhi-Jie Kang, Wen-Jun Fan, Li-Li Zhu, Mei Li, Bai Cui, Fei-Meng Zheng, Hong-Jiang Wang, Eric W-F Lam, Bo Wang, Jie Xu, Quentin Liu
Long noncoding RNA-H19 (H19), an imprinted oncofetal gene, has a central role in carcinogenesis. Hitherto, the mechanism by which H19 regulates cancer stem cells, remains elusive. Here we show that breast cancer stem cells (BCSCs) express high levels of H19, and ectopic overexpression of H19 significantly promotes breast cancer cell clonogenicity, migration and mammosphere-forming ability. Conversely, silencing of H19 represses these BCSC properties. In concordance, knockdown of H19 markedly inhibits tumor growth and suppresses tumorigenesis in nude mice...
January 19, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28076679/molecular-dynamics-simulations-for-deciphering-the-structural-basis-of-recognition-of-pre-let-7-mirnas-by-lin28
#7
Chhaya Sharma, Debasisa Mohanty
LIN28 protein inhibits biogenesis of miRNAs belonging to the let-7 family by binding to precursor forms of miRNAs. Overexpression of LIN28 and low levels of let-7 miRNAs are associated with several forms of cancer cells. We have performed multiple explicit solvent molecular dynamics simulations ranging from 200 to 500 ns in length on different isoforms of preE-let-7 in complex with LIN28 and also in isolation to identify structural features and key specificity-determining residues (SDRs) that are important for the inhibitory role of LIN28...
January 24, 2017: Biochemistry
https://www.readbyqxmd.com/read/28042541/rational-development-of-a-polycistronic-plasmid-with-a-cpg-free-bacterial-backbone-as-a-potential-tool-for-direct-reprogramming
#8
Kianoush Dormiani, Hamid Mir Mohammad Sadeghi, Hojjat Sadeghi-Aliabadi, Mahboobeh Forouzanfar, Hossein Baharvand, Kamran Ghaedi, Mohammad Hossein Nasr-Esfahani
OBJECTIVE: Induced pluripotent stem cells are generated from somatic cells by direct reprogramming. These reprogrammed pluripotent cells have different applications in biomedical fields such as regenerative medicine. Although viral vectors are widely used for efficient reprogramming, they have limited applications in the clinic due to the risk for immunogenicity and insertional mutagenesis. Accordingly, we designed and developed a small, non-integrating plasmid named pLENSO/Zeo as a 2A-mediated polycistronic expression vector...
2017: Cell Journal
https://www.readbyqxmd.com/read/27992407/lin28-phosphorylation-by-mapk-erk-couples-signalling-to-the-post-transcriptional-control-of%C3%A2-pluripotency
#9
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/27934587/generation-of-an-ipsc-line-from-a-patient-with-tyrosine-hydroxylase-th-deficiency-th-1-ipsc
#10
Sabine Jung-Klawitter, Nenad Blau, Attila Sebe, Juliane Ebersold, Gudrun Göhring, Thomas Opladen
Fibroblasts from a male patient with compound heterozygous variants in the tyrosine hydroxylase gene (TH; OMIM: 191290; c.[385-C>T]; [692-G>C]/p.[R129*]; [R231P]), the rate-limiting enzyme for dopamine synthesis, were reprogrammed to iPSCs using episomal reprogramming delivering the reprogramming factors Oct3/4, Sox2, L-Myc, Lin28, Klf4 and p53 shRNA Okita et al. (2011). Pluripotency of TH-1 iPSC was verified by immunohistochemistry and RT-PCR analysis. Cells exhibited a normal karyotype and differentiated spontaneously into the 3 germ layers in vitro...
October 26, 2016: Stem Cell Research
https://www.readbyqxmd.com/read/27931036/clinical-exome-sequencing-reveals-mkrn3-pathogenic-variants-in-familial-and-nonfamilial-idiopathic-central-precocious-puberty
#11
Nelmar Valentina Ortiz-Cabrera, Rosa Riveiro-Álvarez, Miguel Ángel López-Martínez, Pilar Pérez-Segura, Isabel Aragón-Gómez, María José Trujillo-Tiebas, Leandro Soriano-Guillén
BACKGROUND/AIMS: Idiopathic central precocious puberty (ICPP) is the premature activation of the hypothalamic-pituitary-gonadal axis in the absence of organic disease. Up to now, just gain-of-function mutations of KISS1/KISS1R and loss-of-function mutations of the maternally imprinted gene MKRN3 are the known genetic causes of ICPP. Our intention is to evaluate variants present in genes related to the pubertal onset pathway that could act as disease-causing or predisposing variants. METHODS: We studied the clinical exome of 20 patients diagnosed with ICPP using the Illumina platform...
December 9, 2016: Hormone Research in Pædiatrics
https://www.readbyqxmd.com/read/27920151/lin28-is-induced-in-primed-embryonic-stem-cells-and-regulates-let-7-independent-events
#12
Silvia Parisi, Fabiana Passaro, Luigi Russo, Anna Musto, Angelica Navarra, Simona Romano, Giuseppe Petrosino, Tommaso Russo
Lin28 RNA-binding proteins play important roles in pluripotent stem cells, but the regulation of their expression and the mechanisms underlying their functions are still not definitively understood. Here we address the above-mentioned issues in the first steps of mouse embryonic stem cell (ESC) differentiation. We observed that the expression of Lin28 genes is transiently induced soon after the exit of ESCs from the naive ground state and that this induction is due to the Hmga2-dependent engagement of Otx2 with enhancers present at both Lin28 gene loci...
December 5, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/27895551/oct4-methylation-mediated-silencing-as-an-epigenetic-barrier-preventing-m%C3%A3-ller-glia-dedifferentiation-in-a-murine-model-of-retinal-injury
#13
Luis I Reyes-Aguirre, Monica Lamas
Müller glia (MG) is the most abundant glial type in the vertebrate retina. Among its many functions, it is capable of responding to injury by dedifferentiating, proliferating, and differentiating into every cell types lost to damage. This regenerative ability is notoriously absent in mammals. We have previously reported that cultured mammalian MG undergoes a partial dedifferentiation, but fails to fully acquire a progenitor phenotype and differentiate into neurons. This might be explained by a mnemonic mechanism comprised by epigenetic traits, such as DNA methylation...
2016: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/27879219/induced-pluripotent-stem-cells-ipscs-derived-from-cerebrotendinous-xanthomatosis-ctx-patient-s-fibroblasts-carrying-a-r395s-mutation
#14
Philip Höflinger, Stefan Hauser, Yvonne Theurer, Stefanie Weißenberger, Carlo Wilke, Ludger Schöls
Induced pluripotent stem cells (iPSCs) were generated from dermal fibroblasts from a 60-year-old cerebrotendinous xanthomatosis (CTX) patient, carrying a homozygous mutation c. [1183C>A]; p. R395S in CYP27A1. Episomal plasmids encoding the pluripotency genes OCT4, SOX2, KLF4, L-MYC and LIN28 were introduced via electroporation. The generated line iPS-CTX-R395S has no sign of plasmid integration or chromosomal aberration and retained the mutation site in CYP27A1. Furthermore, iPSCs express pluripotency markers and are able to differentiate in all germ layers in vitro...
September 2016: Stem Cell Research
https://www.readbyqxmd.com/read/27879208/generation-of-induced-pluripotent-stem-cells-ipscs-from-a-retinoblastoma-patient-carrying-a-c-2663g-a-mutation-in-rb1-gene
#15
Sicong Zeng, Lvjun Liu, Qi Ouyang, Yan Zhao, Ge Lin, Liang Hu, Wen Li
Skin fibroblasts were obtained from a male patient diagnosed with retinoblastoma (RB) carrying a c.2663G>A mutation in the 25 exon of RB1 gene. RB-iPS cells was generated via delivered four reprogramming factors (OCT4, SOX2, NANOG and LIN28) into these skin fibroblasts. The RB-iPS cells retained the RB1 heterozygous mutation resulted in a truncated RB1 mRNA. Characteristic tests proved that the iPSC line presented typical markers of pluripotency and had the capability to form the three germ layers in vitro...
September 2016: Stem Cell Research
https://www.readbyqxmd.com/read/27822179/plasmid-based-generation-of-induced-neural-stem-cells-from-adult-human-fibroblasts
#16
Philipp Capetian, Luis Azmitia, Martje G Pauly, Victor Krajka, Felix Stengel, Eva-Maria Bernhardi, Mariana Klett, Britta Meier, Philip Seibler, Nancy Stanslowsky, Andreas Moser, Andreas Knopp, Gabriele Gillessen-Kaesbach, Guido Nikkhah, Florian Wegner, Máté Döbrössy, Christine Klein
Direct reprogramming from somatic to neural cell types has become an alternative to induced pluripotent stem cells. Most protocols employ viral expression systems, posing the risk of random genomic integration. Recent developments led to plasmid-based protocols, lowering this risk. However, these protocols either relied on continuous presence of a variety of small molecules or were only able to reprogram murine cells. We therefore established a reprogramming protocol based on vectors containing the Epstein-Barr virus (EBV)-derived oriP/EBNA1 as well as the defined expression factors Oct3/4, Sox2, Klf4, L-myc, Lin28, and a small hairpin directed against p53...
2016: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/27798668/the-lin28-expression-in-stallion-testes
#17
Geumhui Lee, Heejun Jung, Minjung Yoon
The molecular markers for specific germ cell stages can be utilized for identifying, monitoring, and separating a particular stage of germ cells. The RNA-binding protein Lin28 is expressed in gonocytes of human fetal testes. The Lin28 expression is restricted to a very small population of spermatogonial cells in human, mice, and monkey. The main objective of this study was to investigate the expression pattern of Lin28 in stallion testes at different reproductive stages. Based on the presence or absence of full spermatogenesis and lumina in seminiferous tubules, the testicular samples were categorized into two reproductive stages pre-pubertal and post-pubertal...
2016: PloS One
https://www.readbyqxmd.com/read/27789410/lymphoblast-derived-integration-free-ipsc-lines-from-a-female-and-male-alzheimer-s-disease-patient-expressing-different-copy-numbers-of-a-coding-cnv-in-the-alzheimer-risk-gene-cr1
#18
Friederike Schröter, Kristel Sleegers, Caroline Van Cauwenberghe, Martina Bohndorf, Wasco Wruck, Christine Van Broeckhoven, James Adjaye
Human lymphoblast cells from a female and male patient diagnosed with Alzheimer's disease (AD) with different genotypes of a functional copy number variation (CNV) in the AD risk gene CR1 were used to generate integration-free induced pluripotent stem cells (iPSCs) employing episomal plasmids expressing OCT4, SOX2, NANOG, LIN28, c-MYC and L-MYC. The iPSCs retained the CR1 CNV, and comparative transcriptome analyses with the human embryonic stem cell line H1 revealed a Pearson correlation of 0.956 for AD1-CR10 and 0...
October 19, 2016: Stem Cell Research
https://www.readbyqxmd.com/read/27789408/lymphoblast-derived-integration-free-ips-cell-line-from-a-female-67-year-old-alzheimer-s-disease-patient-with-trem2-r47h-missense-mutation
#19
Friederike Schröter, Kristel Sleegers, Elise Cuyvers, Martina Bohndorf, Wasco Wruck, Christine Van Broeckhoven, James Adjaye
Human lymphoblast cells from a female patient diagnosed with Alzheimer's disease (AD) possessing the missense mutation TREM2 p.R47H were used to generate integration-free induced pluripotent stem cells (iPSCs) employing episomal plasmids expressing OCT4, SOX2, NANOG, LIN28, c-MYC and L-MYC. The iPSCs retained the TREM2 mutation, and were defined as pluripotent based on (i) expression of pluripotent-associated markers, (ii) embryoid body-based differentiation into cell types representative of the three germ layers and (iii) the similarity between the transcriptomes of the iPSC line and the human embryonic stem cell line H1 with a Pearson correlation of 0...
October 20, 2016: Stem Cell Research
https://www.readbyqxmd.com/read/27789405/episomal-plasmid-based-generation-of-an-ipsc-line-from-a-79-year-old-individual-carrying-the-apoe4-4-genotype-i11001
#20
Shadaan Zulfiqar, Barbara Fritz, Katja Nieweg
In this study, lymphoblastoid cells derived from a 79-year old individual with a history of progressive presenile dementia, were used to generate iPS cells, employing episomal plasmids expressing OCT4, SOX2, KLF4, LIN28, L-MYC and a p53 shRNA. The individual was homozygous for the APOE4 allele. The resulting iPS cells had a normal karyotype, retained the APOE4/4 genotype, expressed pluripotency markers, were free of genomically integrated plasmids, and could be differentiated into cell type representatives from the three germ layers in vitro...
September 23, 2016: Stem Cell Research
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