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Lin28

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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
#1
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/28768505/tough-decoy-targeting-of-predominant-let-7-mirna-species-in-adult-human-hematopoietic-cells
#2
Jaira F de Vasconcellos, Colleen Byrnes, Y Terry Lee, Joshua M Allwardt, Megha Kaushal, Antoinette Rabel, Jeffery L Miller
BACKGROUND: In humans, the heterochronic cascade composed of the RNA-binding protein LIN28 and its major target, the let-7 family of microRNAs (miRNAs), is highly regulated during human erythroid ontogeny. Additionally, down-regulation of the let-7 miRNAs in cultured adult CD34(+) cells or the over-expression of LIN28 in cultured erythrocytes from pediatric patients with HbSS genotype causes increased levels of fetal hemoglobin (HbF) in the range of 19-40% of the total. Therefore, we hypothesized that focused targeting of individual let-7 miRNA family members would exhibit regulatory effect on HbF expression in human adult erythroblasts...
August 2, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28745393/beyond-an-oncogene-lin28-is-a-master-regulator-of-cancer-progression
#3
REVIEW
Xuefei Wang, Mingjiao Weng, Yinji Jin, Weiwei Yang, Xin Wang, Di Wu, Tianzhen Wang, Xiaobo Li
The RNA binding protein Lin28 is increased in most human malignancies, and elevated Lin28 is a biomarker for poor prognosis and contributes to cancer progression. Lin28 functions as a master oncogene and is involved in almost all hallmarks of cancer. In this review, we summarize the aberrant molecular expression mechanisms and pathological roles of Lin28 in cancer progression. Moreover, we elaborate on the established molecular mechanisms, from the transcriptional level to the post-transcriptional and translational levels, by which Lin28 regulates cancer progression...
July 26, 2017: Histology and Histopathology
https://www.readbyqxmd.com/read/28737214/decline-in-cellular-function-of-aged-mouse-c-kit-cardiac-progenitor-cells
#4
Alessandra Castaldi, Ramsinh Mansinh Dodia, Amabel M Orogo, Cristina M Zambrano, Rita H Najor, Åsa B Gustafsson, Joan Heller Brown, Nicole H Purcell
Therapeutic use of c-kit(+) cardiac progenitor cells (CPCs) is being evaluated for regenerative therapy in older patients with ischemic heart failure. Our understanding of the biology of these CPCs has however, largely come from studies of young cells and animal models. In the present study we examined characteristics of CPCs isolated from young (3 months) and aged (24 month) mice that could underlie the diverse outcomes reported for CPC-based therapeutics. We observed morphological differences and altered senescence indicated by increased senescence associated markers β-galactosidase and p16 mRNA in aged CPCs...
July 24, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28732738/association-of-microrna-125a-and-microrna-499a-polymorphisms-in-chronic-periodontitis-in-a-sample-south-indian-population-a-hospital-based-genetic-association-study
#5
Priyanka Venugopal, Vamsi Lavu, Suresh Ranga Rao, Vettriselvi Venkatesan
Periodontitis is a chronic inflammatory disease, caused by interaction between periodontopathic bacteria and the host immune response. MicroRNAs are small, single-stranded molecules, which play a key role in the regulation of diverse biological processes. Dysregulation of microRNAs function can lead to several diseases such as autoimmune and chronic inflammatory diseases. The objective of the study was to determine the association between selected single nucleotide polymorphisms in miR-125a, miR-499 and LIN28 homology A with chronic periodontitis susceptibility in a sample population from south India...
July 18, 2017: Gene
https://www.readbyqxmd.com/read/28703793/linc-dync2h1-4-promotes-emt-and-csc-phenotypes-by-acting-as-a-sponge-of-mir-145-in-pancreatic-cancer-cells
#6
Yuran Gao, Zhicheng Zhang, Kai Li, Liying Gong, Qingzhu Yang, Xuemei Huang, Chengcheng Hong, Mingfeng Ding, Huanjie Yang
The acquisition of epithelial-mesenchymal transition (EMT) and/or existence of a sub-population of cancer stem-like cells (CSC) are associated with malignant behavior and chemoresistance. To identify which factor could promote EMT and CSC formation and uncover the mechanistic role of such factor is important for novel and targeted therapies. In the present study, we found that the long intergenic non-coding RNA linc-DYNC2H1-4 was upregulated in pancreatic cancer cell line BxPC-3-Gem with acquired gemcitabine resistance...
July 13, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28683410/different-expression-patterns-of-lin28-and-lin28b-in-mouse-molar-development
#7
Ning Dong, Yan Liu, Tiantian Zhang, Lin Zhao, Jiangang Tian, Jianping Ruan
OBJECTIVE: The RNA-binding proteins Lin28 and Lin28b are expressed in many developing tissues and are involved in the biosynthesis of the microRNA let-7 family and embryogenesis processes. However, their roles in mammalian tooth development remain ill-defined. DESIGN: The spatiotemporal expressions of Lin28 and Lin28b during mouse molar odontogenesis from day E11.5 to P21 were examined through immunohistochemistry and western blot analysis. RESULTS: Both Lin28 and Lin28b were initially expressed in dental epithelium, but the expression patterns varied thereafter...
June 23, 2017: Archives of Oral Biology
https://www.readbyqxmd.com/read/28677541/generation-of-induced-pluripotent-stem-cell-ipsc-line-from-a-36-year-old-charcot-marie-tooth-disease-patient-with-gjb1-mutation-cmtx
#8
Daryeon Son, Phil Jun Kang, Wonjin Yun, Seungkwon You
Charcot-Marie-Tooth disease (CMTX) is inherited neurological disorder caused by gap junction beta 1 gene (GJB1) mutation. We generated induced pluripotent stem cell (iPSC) line from 36-year-old CMTX disease patient by electroporation of skin fibroblasts with episomal vectors encoding OCT4, SOX2, KLF4, L-MYC, LIN28 and shRNA-p53. Established iPSCs expressed various pluripotency markers, had differentiation potential of three germ layers in vitro, had normal karyotype and retained GJB1 mutation. This CMT patient-derived iPSC line could be useful in vitro tool for CMTX research as disease modeling and drug development...
May 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28671666/multi-domain-utilization-by-tut4-and-tut7-in-control-of-let-7-biogenesis
#9
Christopher R Faehnle, Jack Walleshauser, Leemor Joshua-Tor
The uridyl transferases TUT4 and TUT7 (collectively called TUT4(7)) switch between two modes of activity, either promoting expression of let-7 microRNA (monoU) or marking it for degradation (oligoU). Lin28 modulates the switch via recruitment of TUT4(7) to the precursor pre-let-7 in stem cells and human cancers. We found that TUT4(7) utilize two multidomain functional modules during the switch from monoU to oligoU. The catalytic module (CM) is essential for both activities, while the Lin28-interacting module (LIM) is indispensable for oligoU...
August 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28669602/the-bile-acid-nuclear-receptor-fxr%C3%AE-is-a-critical-regulator-of-mouse-germ-cell-fate
#10
Emmanuelle Martinot, Lauriane Sèdes, Marine Baptissart, Hélène Holota, Betty Rouaisnel, Christelle Damon-Soubeyrand, Angélique De Haze, Jean-Paul Saru, Christelle Thibault-Carpentier, Céline Keime, Jean-Marc A Lobaccaro, Silvère Baron, Gérard Benoit, Françoise Caira, Claude Beaudoin, David H Volle
Spermatogenesis is the process by which spermatozoa are generated from spermatogonia. This cell population is heterogeneous, with self-renewing spermatogonial stem cells (SSCs) and progenitor spermatogonia that will continue on a path of differentiation. Only SSCs have the ability to regenerate and sustain spermatogenesis. This makes the testis a good model to investigate stem cell biology. The Farnesoid X Receptor alpha (FXRα) was recently shown to be expressed in the testis. However, its global impact on germ cell homeostasis has not yet been studied...
July 11, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28665509/direct-reprogramming-of-human-suspension-cells-into-mesodermal-cell-lineages-via-combined-magnetic-targeting-and-photothermal-stimulation-by-magnetic-graphene-oxide-complexes
#11
Min-Yu Chiang, Yi-Zhen Lin, Shwu-Jen Chang, Woei-Cherng Shyu, Huai-En Lu, San-Yuan Chen
Suspension cells can provide a source of cells for cellular reprogramming, but they are difficult to transfect by nonviral vectors. An efficient and safe nonviral vector (GO-Fe3 O4 -PEI complexes) based on iron oxide nanoparticle (Fe3 O4 )-decorated graphene oxide (GO) complexed with polyethylenimine (PEI) for the first time is developed for delivering three individual episomal plasmids (pCXLE-hOCT3/4-shp53, pCXLE-hSK, and pCXLE-hUL) encoding pluripotent-related factors of Oct3/4, shRNA against p53, Sox2, Klf4, L-Myc, and Lin28 into human peripheral blood mononuclear cells (PBMCs) simultaneously...
June 30, 2017: Small
https://www.readbyqxmd.com/read/28635509/induced-pluripotent-stem-cell-derived-dopaminergic-neurons-from-adult-common-marmoset-fibroblasts
#12
Scott C Vermilyea, Scott Guthrie, Michael Meyer, Kim Smuga-Otto, Katarina Braun, Sara Howden, James A Thomson, Su-Chun Zhang, Marina Emborg, Dr Thaddeus G Golos
The common marmoset monkey (Callithrix jacchus; Cj) is an advantageous nonhuman primate species for modeling age-related disorders, including Parkinson's disease, due to their shorter lifespan compared to macaques. Cj-derived induced pluripotent stem cells (Cj-iPSCs) from somatic cells are needed for in vitro disease modeling and testing regenerative medicine approaches. Here we report the development of a novel Cj-iPSC line derived from adult marmoset fibroblasts. The Cj-iPSCs showed potent pluripotency properties including development of mesodermal lineages in tumors after injection to immunocompromised mice, as well as ectoderm and endoderm lineages after in vitro differentiation regimens, demonstrating differentiated derivatives of all three embryonic layers...
June 21, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/28632762/dot1l-inhibitor-improves-early-development-of-porcine-somatic-cell-nuclear-transfer-embryos
#13
Jia Tao, Yu Zhang, Xiaoyuan Zuo, Renyun Hong, Hui Li, Xing Liu, Weiping Huang, Zubing Cao, Yunhai Zhang
Incomplete epigenetic reprogramming of the genome of donor cells causes poor early and full-term developmental efficiency of somatic cell nuclear transfer (SCNT) embryos. Previous research indicate that inhibition of the histone H3 K79 methyltransferase DOT1L, using a selective pharmacological inhibitor EPZ004777 (EPZ), significantly improved reprogramming efficiency during the generation of mouse induced pluripotent stem cells. However, the roles of DOT1L in porcine nuclear transfer-mediated cellular reprogramming are not yet known...
2017: PloS One
https://www.readbyqxmd.com/read/28618452/murine-melanoma-cells-incomplete-reprogramming-using-non-viral-vector
#14
D A D Câmara, A S Porcacchia, A S Costa, R A Azevedo, I Kerkis
OBJECTIVES: The reprogramming of cancer cells into induced pluripotent stem cells or less aggressive cancer cells can provide a modern platform to study cancer-related genes and their interactions with cell environment before and after reprogramming. Herein, we aimed to investigate the reprogramming capacity of murine melanoma B16F10 cells. MATERIALS AND METHODS: The B16F10 was transfected using non-viral circular DNA plasmid containing the genes Sox-2, Oct4, Nanog, Lin28 and green fluorescent protein (GFP)...
June 15, 2017: Cell Proliferation
https://www.readbyqxmd.com/read/28614211/mixed-gonadal-germ-cell-tumor-composed-of-a-spermatocytic-tumor-like-component-and-germinoma-arising-in-gonadoblastoma-in-a-phenotypic-woman-with-a-46-xx-peripheral-karyotype-report-of-the-first-case
#15
Alejandro A Gru, Eli S Williams, Dengfeng Cao
We report a unique case of gonadal mixed germ cell tumor (GCT) composed of a predominantly spermatocytic tumor (ST)-like component and a minor component of germinoma arising in gonadoblastoma in a phenotypic woman with a 46, XX peripheral karotype. The patient was a 24-year-old woman (gravida 2, para 1) found to have a 7 cm pelvic mass during routine obstetric ultrasound examination at 20 weeks gestational age. She underwent a left salpingo-gonadectomy at gestational age 23 and 2/7 weeks. She recovered well and delivered a healthy baby at full term...
September 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28596507/let-7g-suppresses-both-canonical-and-non-canonical-nf-%C3%AE%C2%BAb-pathways-in-macrophages-leading-to-anti-atherosclerosis
#16
Yung-Song Wang, Edward Hsi, Hsin-Yun Cheng, Shih-Hsien Hsu, Yi-Chu Liao, Suh-Hang H Juo
Transformation of macrophages to foam cells contributes to atherosclerosis. Here, we report that let-7g reduces macrophage transformation and alleviates foam cell apoptosis by suppressing both canonical and non-canonical NF-κB pathways. In the canonical pathway, let-7g inhibits phosphorylation of IKKβ and IκB, down-regulates SREBF2 and miR-33a, and up-regulates ABCA1. In the non-canonical pathway, let-7g directly knocks down MEKK1, IKKα and ablates IKKα phosphorylation. Let-7g's effects in macrophages can be almost completely blocked by inactivation of NF-κB signaling, which suggests that let-7g's effects are primarily mediated through the suppression of NF-κB pathways...
May 23, 2017: Oncotarget
https://www.readbyqxmd.com/read/28583172/fluorescent-tagged-episomals-for-stoichiometric-induced-pluripotent-stem-cell-reprogramming
#17
Christopher E Schmitt, Blanca M Morales, Ellen M H Schmitz, John S Hawkins, Carlos O Lizama, Joan P Zape, Edward C Hsiao, Ann C Zovein
BACKGROUND: Non-integrating episomal vectors have become an important tool for induced pluripotent stem cell reprogramming. The episomal vectors carrying the "Yamanaka reprogramming factors" (Oct4, Klf, Sox2, and L-Myc + Lin28) are critical tools for non-integrating reprogramming of cells to a pluripotent state. However, the reprogramming process remains highly stochastic, and is hampered by an inability to easily identify clones that carry the episomal vectors. METHODS: We modified the original set of vectors to express spectrally separable fluorescent proteins to allow for enrichment of transfected cells...
June 5, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28582547/the-torc1-2-inhibitor-tak228-sensitizes-atypical-teratoid-rhabdoid-tumors-to-cisplatin-induced-cytotoxicity
#18
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
#19
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/28557624/rna-guided-activation-of-pluripotency-genes-in-human-fibroblasts
#20
Kai Xiong, Yan Zhou, Kristian Aabo Blichfeld, Poul Hyttel, Lars Bolund, Kristine Karla Freude, Yonglun Luo
Specific activation of endogenous genes can be achieved by programmable artificial transcription factors (ATFs). In this study, we compared two artificial, programmable, clustered regularly interspaced short palindromic repeats (CRISPR)-based, ubiquitous transcription factors: deficient CRISPR-associated protein 9 (dCas9)-VP64 (CRISPRa) alone, or a combination of dCas9-VP64 and MS2-P65-HSF1 [synergistic activation mediator (SAM) system] mediated activation of five pluripotency genes: KLF4 (K), LIN28 (L), MYC (M), OCT4 (O), and SOX2 (S) in human cells (HEK293T, HeLa, HepG2, and primary fibroblasts)...
June 2017: Cellular Reprogramming
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