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Lin28A

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https://www.readbyqxmd.com/read/28049690/rewiring-of-embryonic-glucose-metabolism-via-suppression-of-pfk-1-and-aldolase-during-mouse-chorioallantoic-branching
#1
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
#2
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
#3
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
#4
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
#5
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-positively-and-negatively-mirna-levels
#6
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...
November 23, 2016: 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
#7
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 1115 cases and 1173 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...
November 18, 2016: Genes, Chromosomes & Cancer
https://www.readbyqxmd.com/read/27793004/comparison-of-the-expression-and-function-of-lin28a-and-lin28b-in-colon-cancer
#8
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...
October 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/27721018/musashi-2-contributes-to-the-stemness-and-chemoresistance-of-liver-cancer-stem-cells-via-lin28a-activation
#9
Tian Fang, Hongwei Lv, Fuquan Wu, Changzheng Wang, Ting Li, Guishuai Lv, Liang Tang, Linna Guo, Shanhua Tang, Dan Cao, Mengchao Wu, Wen Yang, Hongyang Wang
Accumulating evidence suggests that cancer stem cells (CSCs), a small subset of cancer cells, are responsible for tumor initiation, progression, relapse and metastasis. Musashi 2 (MSI2), a RNA-binding protein, was proposed to be a potent oncogene playing key roles in myeloid leukemia and gastrointestinal malignancies. However, it remains elusive how MSI2 regulates stem cell features in HCC. Herein, we demonstrated that MSI2 was highly expressed in liver CSCs. Overexpression or knockdown of MSI2 altered CSC-related gene expression, self-renewal as well as resistance to chemotherapy in HCC cell lines...
January 1, 2017: Cancer Letters
https://www.readbyqxmd.com/read/27693787/lin28a-protects-against-postinfarction-myocardial-remodeling-and-dysfunction-through-sirt1-activation-and-autophagy-enhancement
#10
Yuanyuan Hao, Qun Lu, Guodong Yang, Aiqun Ma
BACKGROUND: Myocardial remodeling and cardiac dysfunction prevention may represent a therapeutic approach to reduce mortality in patients with myocardial infarction (MI). We investigated the effects of Lin28a in experimental MI models, as well as the mechanisms underlying these effects. METHODS: Left anterior descending (LAD) coronary artery ligation was used to construct an MI-induced injury model. Neonatal cardiomyocytes were isolated and cultured to investigate the mechanisms underlying the protective effects of Lin28a against MI-induced injury...
October 28, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27636107/cdk1-pdk1-pi3k-akt-signaling-pathway-regulates-embryonic-and-induced-pluripotency
#11
Xiao Qi Wang, Chung Mau Lo, Lin Chen, Elly S-W Ngan, Aimin Xu, Randy Yc Poon
The mechanisms of how signaling pathways are coordinated and integrated for the maintenance of the self-renewal of human embryonic stem cells (hESCs) and the acquisition of pluripotency in reprogramming are still only partly understood. CDK1 is a key regulator of mitosis. Recently, CDK1 has been shown to be involved in regulating self-renewal of stem cells, even though the mechanistic role of how CDK1 regulates pluripotency is unknown. In this report, we aim to understand how CDK1 can control pluripotency by reducing CDK1 activity to a level that has no effect on cell cycle progression...
January 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/27559824/human-lin28-forms-a-high-affinity-1-1-complex-with-the-106-363-cluster-mirna-mir-363
#12
Daniel T Peters, Herman K H Fung, Vladimir M Levdikov, Tobias Irmscher, Fiona C Warrander, Sandra J Greive, Oleg Kovalevskiy, Harry V Isaacs, Mark Coles, Alfred A Antson
Lin28A is a post-transcriptional regulator of gene expression that interacts with and negatively regulates the biogenesis of let-7 family miRNAs. Recent data suggested that Lin28A also binds the putative tumor suppressor miR-363, a member of the 106~363 cluster of miRNAs. Affinity for this miRNA and the stoichiometry of the protein-RNA complex are unknown. Characterization of human Lin28's interaction with RNA has been complicated by difficulties in producing stable RNA-free protein. We have engineered a maltose binding protein fusion with Lin28, which binds let-7 miRNA with a Kd of 54...
September 13, 2016: Biochemistry
https://www.readbyqxmd.com/read/27538419/lin28a-enhances-the-therapeutic-potential-of-cultured-neural-stem-cells-in-a-parkinson-s-disease-model
#13
Yong-Hee Rhee, Tae-Ho Kim, A-Young Jo, Mi-Yoon Chang, Chang-Hwan Park, Sang-Mi Kim, Jae-Jin Song, Sang-Min Oh, Sang-Hoon Yi, Hyeon Ho Kim, Bo-Hyun You, Jin-Wu Nam, Sang-Hun Lee
The original properties of tissue-specific stem cells, regardless of their tissue origins, are inevitably altered during in vitro culturing, lessening the clinical and research utility of stem cell cultures. Specifically, neural stem cells derived from the ventral midbrain lose their dopamine neurogenic potential, ventral midbrain-specific phenotypes, and repair capacity during in vitro cell expansion, all of which are critical concerns in using the cultured neural stem cells in therapeutic approaches for Parkinson's disease...
August 18, 2016: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/27528750/the-role-of-trim25-in-development-disease-and-rna-metabolism
#14
REVIEW
Gregory Heikel, Nila Roy Choudhury, Gracjan Michlewski
Trim25 is a member of the tripartite motif family of E3 ubiquitin ligases. It plays major roles in innate immunity and defence against viral infection, control of cell proliferation and migration of cancer cells. Recent work identified Trim25 as being able to bind to RNA and to regulate Lin28a-mediated uridylation of pre-let-7. Here we review the current knowledge of the role of Trim25 in development, disease and RNA metabolism.
August 15, 2016: Biochemical Society Transactions
https://www.readbyqxmd.com/read/27494865/lin28a-activates-androgen-receptor-via-regulation-of-c-myc-and-promotes-malignancy-of-er-her2-breast-cancer
#15
Honghong Shen, Lin Zhao, Xiaolong Feng, Cong Xu, Congying Li, Yun Niu
Having previously demonstrated the co-expression status of the Lin28A and androgen receptor (AR) in ER-/Her2+ breast cancer, we tested the hypothesis that Lin28A can activate AR and promotes growth of ER-/Her2+ breast cancer. The expression of Lin28A and AR were examined after Lin28A siRNA and Lin28A plasmid were transfected into ER-/Her2+ breast cancer cells. Chromatin immune-precipitation (ChIP) analysis and Luciferase Assays were used to evaluate the effect of Lin28A and c-myc on AR promoter activity. MTT assays, Boyden chamber invasion assays, colony formation assays and flow cytometry analysis were performed...
September 13, 2016: Oncotarget
https://www.readbyqxmd.com/read/27469285/stemness-of-spermatogonial-stem-cells-encapsulated-in-alginate-hydrogel-during-cryopreservation
#16
A Pirnia, K Parivar, M Hemadi, P Yaghmaei, M Gholami
This study investigated the effect of spermatogonial stem cell encapsulated in alginate hydrogel during cryopreservation, as cells were protected against damage during cryopreservation within the hydrogel. Spermatogonial stem cells were isolated from the testes of Balb/c mice pups (6 days old), purified in laminin-coated dishes and CD90.1 microbeads, encapsulated in alginate hydrogel and then cryopreserved. After thawing, cell viability and Spermatogonial stem cell (SSC) colony diameter were evaluated. After RNA was isolated and cDNA was synthesised, the expression of stemness genes was considered using RT real-time PCR...
July 29, 2016: Andrologia
https://www.readbyqxmd.com/read/27320042/lin28-regulates-stem-cell-metabolism-and-conversion-to-primed-pluripotency
#17
Jin Zhang, Sutheera Ratanasirintrawoot, Sriram Chandrasekaran, Zhaoting Wu, Scott B Ficarro, Chunxiao Yu, Christian A Ross, Davide Cacchiarelli, Qing Xia, Marc Seligson, Gen Shinoda, Wen Xie, Patrick Cahan, Longfei Wang, Shyh-Chang Ng, Supisara Tintara, Cole Trapnell, Tamer Onder, Yuin-Han Loh, Tarjei Mikkelsen, Piotr Sliz, Michael A Teitell, John M Asara, Jarrod A Marto, Hu Li, James J Collins, George Q Daley
The RNA-binding proteins LIN28A and LIN28B play critical roles in embryonic development, tumorigenesis, and pluripotency, but their exact functions are poorly understood. Here, we show that, like LIN28A, LIN28B can function effectively with NANOG, OCT4, and SOX2 in reprogramming to pluripotency and that reactivation of both endogenous LIN28A and LIN28B loci are required for maximal reprogramming efficiency. In human fibroblasts, LIN28B is activated early during reprogramming, while LIN28A is activated later during the transition to bona fide induced pluripotent stem cells (iPSCs)...
July 7, 2016: Cell Stem Cell
https://www.readbyqxmd.com/read/27230676/lin28a-induces-energetic-switching-to-glycolytic-metabolism-in-human-embryonic-kidney-cells
#18
Craig K Docherty, Ian P Salt, John R Mercer
BACKGROUND: Loss of a cell's capacity to generate sufficient energy for cellular functions is a key hallmark of the ageing process and ultimately leads to a variety of important age-related pathologies such as cancer, Parkinson's disease and atherosclerosis. Regenerative medicine has sought to reverse these pathologies by reprogramming somatic cells to a more juvenile energetic state using a variety of stem cell factors. One of these factors, Lin28, is considered a candidate for modification in the reprogramming of cellular energetics to ameliorate the ageing process while retaining cell phenotype...
May 26, 2016: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/27197175/activation-of-the-lin28-let-7-axis-by-loss-of-ese3-ehf-promotes-a-tumorigenic-and-stem-like-phenotype-in-prostate-cancer
#19
Domenico Albino, Gianluca Civenni, Cecilia Dallavalle, Martina Roos, Hartmut Jahns, Laura Curti, Simona Rossi, Sandra Pinton, Gioacchino D'Ambrosio, Fausto Sessa, Jonathan Hall, Carlo V Catapano, Giuseppina M Carbone
Although cancer stem-like cells (CSC) are thought to be the most tumorigenic, metastatic, and therapy-resistant cell subpopulation within human tumors, current therapies target bulk tumor cells while tending to spare CSC. In seeking to understand mechanisms needed to acquire and maintain a CSC phenotype in prostate cancer, we investigated connections between the ETS transcription factor ESE3/EHF, the Lin28/let-7 microRNA axis, and the CSC subpopulation in this malignancy. In normal cells, we found that ESE3/EHF bound and repressed promoters for the Lin28A and Lin28B genes while activating transcription and maturation of the let-7 microRNAs...
June 15, 2016: Cancer Research
https://www.readbyqxmd.com/read/27184842/the-rna-binding-protein-imp2-preserves-glioblastoma-stem-cells-by-preventing-let-7-target-gene-silencing
#20
Nils Degrauwe, Tommy B Schlumpf, Michalina Janiszewska, Patricia Martin, Alexandra Cauderay, Paolo Provero, Nicolo Riggi, Mario-L Suvà, Renato Paro, Ivan Stamenkovic
Cancer stem cells (CSCs) can drive tumor growth, and their maintenance may rely on post-transcriptional regulation of gene expression, including that mediated by microRNAs (miRNAs). The let-7 miRNA family has been shown to induce differentiation by silencing stem cell programs. Let-7-mediated target gene suppression is prevented by LIN28A/B, which reduce let-7 biogenesis in normal embryonic and some cancer stem cells and ensure maintenance of stemness. Here, we find that glioblastoma stem cells (GSCs) lack LIN28 and express both let-7 and their target genes, suggesting LIN28-independent protection from let-7 silencing...
May 24, 2016: Cell Reports
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