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Lin28

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https://www.readbyqxmd.com/read/29902745/lymphoblast-derived-integration-free-ipsc-line-ad-trem2-3-from-a-74-year-old-alzheimer-s-disease-patient-expressing-the-trem2-p-r47h-variant
#1
Soraia Martins, Hatice Yigit, Martina Bohndorf, Nina Graffmann, Aurelian Robert Fiszl, Wasco Wruck, Kristel Sleegers, Christine Van Broeckhoven, James Adjaye
Human lymphoblast cells from a male diagnosed with Alzheimer's disease (AD) expressing the TREM2 p.R47H variant were used to generate integration-free induced pluripotent stem cells (iPSCs) by over-expressing episomal-based plasmids harbouring OCT4, SOX2, KLF4, LIN28, L-MYC and p53 shRNA. The derived iPSC line - AD-TREM2-3 was defined as pluripotent based on (i) expression of pluripotency-associated markers (ii) embryoid body-based differentiation into cell types representative of the three germ layers and (iii) the similarity between the transcriptome of the iPSC line and the human embryonic stem cell line H1 with a Pearson correlation of 0...
June 1, 2018: Stem Cell Research
https://www.readbyqxmd.com/read/29874593/small-molecule-inhibitors-disrupt-let-7-oligouridylation-and-release-the-selective-blockade-of-let-7-processing-by-lin28
#2
Longfei Wang, R Grant Rowe, Adriana Jaimes, Chunxiao Yu, Yunsun Nam, Daniel S Pearson, Jin Zhang, Xiangyu Xie, William Marion, Gregory J Heffron, George Q Daley, Piotr Sliz
LIN28 is an RNA-binding protein that regulates the maturation of the let-7 family of microRNAs by bipartite interactions with let-7 precursors through its two distinct cold shock and zinc-knuckle domains. Through inhibition of let-7 biogenesis, LIN28 functions as a pluripotency factor, as well as a driver of tumorigenesis. Here, we report a fluorescence polarization assay to identify small-molecule inhibitors for both domains of LIN28 involved in let-7 interactions. Of 101,017 compounds screened, six inhibit LIN28:let-7 binding and impair LIN28-mediated let-7 oligouridylation...
June 5, 2018: Cell Reports
https://www.readbyqxmd.com/read/29852467/derivation-of-an-induced-pluripotent-stem-cell-line-musii004-a-from-dermal-fibroblasts-of-a-48-year-old-spinocerebellar-ataxia-type-3-patient
#3
Alisa Ritthaphai, Methichit Wattanapanitch, Manop Pithukpakorn, Worapa Heepchantree, Rungtip Soi-Ampornkul, Panchalee Mahaisavariya, Daranporn Triwongwaranat, Kovit Pattanapanyasat, Chinnavuth Vatanashevanopakorn
Dermal fibroblasts were obtained from a 48-year-old female patient with spinocerebellar ataxia type 3 (SCA3). Fibroblasts were reprogrammed by nucleofection with episomal plasmids, carrying L-MYC, LIN28, OCT4, SOX2, KLF4, EBNA-1 and shRNA against p53. The SCA3 patient-specific iPSC line, MUSIi004-A, was characterized by immunofluorescence staining to verify the expression of pluripotent markers. The iPSC line exhibited an ability to differentiate into three germ layers by embryoid body (EB) formation. Karyotypic analysis of the MUSIi004-A line was normal...
May 21, 2018: Stem Cell Research
https://www.readbyqxmd.com/read/29770701/mk2-mediates-macrophage-activation-and-acute-lung-injury-by-regulating-let-7e-mirna
#4
Yaxian Wu, Huiqiong He, Yunhe Ding, Sirui Liu, Depeng Zhang, Jun Wang, Hongchao Jiang, Dan Zhang, Lei Sun, Richard D Ye, Feng Qian
MAPK-activated protein kinase 2 (MK2) plays a critical role in the development of inflammation. However, the modulatory mechanisms in macrophage activation and acute lung injury (ALI) haven't been completely defined. Here, we reported that MK2 deficient mice (MK2-/-) protected against sepsis-induced ALI. In response to lipopolysaccharide (LPS) challenge, MK2-/- mice and myeloid cell-specific MK2 conditional knockout mice (MK2Lyz2-KO) exhibited attenuated inflammatory response, especially producing fewer amounts of tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and macrophage inflammatory protein 2 (MIP-2)...
May 17, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/29764469/chibby-suppresses-aerobic-glycolysis-and-proliferation-of-nasopharyngeal-carcinoma-via-the-wnt-%C3%AE-catenin-lin28-let7-pdk1-cascade
#5
Cheng-Fu Cai, Guo-Dong Ye, Dong-Yan Shen, Wei Zhang, Mao-Li Chen, Xin-Xin Chen, Da-Xiong Han, Yan-Jun Mi, Qi-Cong Luo, Wang-Yu Cai, Shu-Yu Yang
BACKGROUND: Great progress has been achieved in the study of the aerobic glycolysis or the so-called Warburg effect in a variety of cancers; however, the regulation of the Warburg effect in Nasopharyngeal carcinoma (NPC) has not been completely defined. METHODS: Gene expression pattern of NPC cells were used to test associations between Chibby and β-catenin expression. Chibby siRNAs and over-expression vector were transfected into NPC cells to down-regulate or up-regulate Chibby expression...
May 15, 2018: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/29758594/phox2b-is-a-reliable-immunomarker-in-distinguishing-peripheral-neuroblastic-tumors-from-cns-embryonal-tumors
#6
Sanda Alexandrescu, Vera Paulson, Adrian Dubuc, Azra Ligon, Hart G Lidov
INTRODUCTION: The PHOX2B gene regulates neuronal maturation in the brain stem nuclei associated with cardiorespiratory function, and in the autonomic sympathetic and enteric nervous system. PHOX2B expression is a reliable immunomarker for peripheral neuroblastic tumors, however no systematic evaluation of CNS embryonal tumors was included in the studies. We encountered two cases in which the differential diagnosis included neuroblastoma and CNS embryonal tumor, and we hypothesized that PHOX2B immunostain would be helpful establishing the diagnosis...
May 14, 2018: Histopathology
https://www.readbyqxmd.com/read/29758178/lin28a-regulates-neurogliogenesis-in-mammalian-retina-through-the-igf-signaling
#7
Xiaohuan Xia, Pooja Teotia, Iqbal Ahmad
In the developing central nervous system (CNS) the majority of neurons are born before the generation of glia. Emerging evidence implicates heterochronic gene, Lin28 in the temporal switch between two distinct lineages. However, the respective contributions of Lin28a and Lin28b in neurogliogenesis remain poorly understood. Here, we have examined the relative involvement of Lin28a and Lin28b in mammalian retina, a simple and accessible CNS model where neurogliogenic decision largely occurs postnatally. Examination of Lin28a/b involvement during late histogenesis by the perturbation of function approaches revealed that while Lin28b did not influence differentiation in general Lin28a facilitated and antagonized the generation of neurons and glia, respectively...
May 11, 2018: Developmental Biology
https://www.readbyqxmd.com/read/29753273/generation-of-an-induced-pluripotent-stem-cell-line-from-a-patient-with-non-syndromic-cln3-associated-retinal-degeneration-and-a-coisogenic-control-line
#8
Xiao Zhang, Dan Zhang, Shang-Chih Chen, Tina Lamey, Jennifer A Thompson, Terri McLaren, John N De Roach, Fred K Chen, Samuel McLenachan
We report the generation of the human iPSC line LEIi004-A from a patient with late-onset non-syndromic retinitis pigmentosa caused by compound heterozygous mutations in the CLN3 gene. Reprogramming of primary dermal fibroblasts was performed using episomal plasmids containing OCT4, SOX2, KLF4, L-MYC, LIN28, shRNA for p53 and mir302/367 microRNA. To create a coisogenic control line, one CLN3 variant was corrected in the patient-iPSC using CRISPR/Cas9 gene editing to generate the iPSC line LEIi004-A-1.
May 1, 2018: Stem Cell Research
https://www.readbyqxmd.com/read/29742265/antiproliferative-effect-of-urolithin-a-the-ellagic-acid-derived-colonic-metabolite-on-hepatocellular-carcinoma-hepg2-2-15-cells-by-targeting-lin28a-let-7a-axis
#9
Zhenpeng Qiu, Junxuan Zhou, Cong Zhang, Ye Cheng, Junjie Hu, Guohua Zheng
An abnormality in the Lin28/let-7a axis is relevant to the progression of hepatitis B virus (HBV)-positive hepatocellular carcinoma (HCC), which could be a novel therapeutic target for this malignant tumor. The present study aimed to investigate the antiproliferative and anti-invasive effects of urolithin A in a stable full-length HBV gene integrated cell line HepG2.2.15 using CCK-8 and transwell assays. The RNA and protein expressions of targets were assessed by quantitative PCR and western blot, respectively...
2018: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
https://www.readbyqxmd.com/read/29724816/modulation-of-lin28b-let-7-signaling-by-propranolol-contributes-to-infantile-hemangioma-involution
#10
Ezinne Francess Mong, Kemal Marc Akat, John Canfield, John Lockhart, Jeffrey VanWye, Andrew Matar, John C M Tsibris, June Wu, Thomas Tuschl, Hana Totary-Jain
OBJECTIVE: Infantile hemangiomas (IHs) are the most common benign vascular neoplasms of infancy, characterized by a rapid growth phase followed by a spontaneous involution, or triggered by propranolol treatment by poorly understood mechanisms. LIN28/let-7 axis plays a central role in the regulation of stem cell self-renewal and tumorigenesis. However, the role of LIN28B/let-7 signaling in IH pathogenesis has not yet been elucidated. APPROACH AND RESULTS: LIN28B is highly expressed in proliferative IH and is less expressed in involuted and in propranolol-treated IH samples as measured by immunofluorescence staining and quantitative RT-PCR...
May 3, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/29689270/mutual-suppression-of-mir-125a-and-lin28b-in-human-hepatocellular-carcinoma-cells
#11
Marta Panella, Nicola Mosca, Armando Di Palo, Nicoletta Potenza, Aniello Russo
MicroRNA-125a exhibits an antiproliferative activity and is downregulated in several types of tumors, including hepatocellular carcinoma where it targets sirtuin-7, matrix metalloproteinase-11, and c-Raf. Another target of miR-125a is Lin28, a pluripotency factor that is generally undetectable in differentiated cells but is often upregulated/reactivated in tumors where it acts as an oncogenic factor promoting cell proliferation and tumor progression. In this study we show that downregulation of Lin28b by miR-125a partially accounts for its antiproliferative activity toward hepatocellular carcinoma cells...
June 7, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29603519/comparison-of-two-different-culture-conditions-for-derivation-of-early-hipsc
#12
Caroline A B Hey, Katarina B Saltõkova, Hanne C Bisgaard, Lisbeth B Møller
Different culture-systems for derivation of induced pluripotent stem cells (iPSC) in vitro from human fibroblasts have been established. Here, we compared the efficacy of two different feeder-free culture-systems; Matrigel-coated surfaces in combination with mTeSR1 medium versus Vitronectin-coated surfaces in combination with Essential 8 (E8) medium. The comparison was performed by counting the number of emerging iPSC-looking colonies of re-programmed fibroblasts. The fibroblasts were re-programmed using episomal plasmids expressing OCT3/4, SOX2, KLF4, L-MYC, LIN28, and a p53 knock down shP53...
March 30, 2018: Cell Biology International
https://www.readbyqxmd.com/read/29602048/lymphoblast-derived-integration-free-ipsc-line-ad-trem2-1-from-a-67year-old-alzheimer-s-disease-patient-expressing-the-trem2-p-r47h-variant
#13
Soraia Martins, Hatice Yigit, Martina Bohndorf, Nina Graffmann, Aurelian Robert Fiszl, Wasco Wruck, Kristel Sleegers, Christine Van Broeckhoven, James Adjaye
Human lymphoblast cells from a male diagnosed with Alzheimer's disease (AD) expressing the TREM2 p.R47H variant were used to generate integration-free induced pluripotent stem cells (iPSCs) by over-expressing episomal-based plasmids harbouring OCT4, SOX2, NANOG, LIN28, c-MYC and L-MYC. AD-TREM2-1 was defined as pluripotent based on (i) expression of pluripotency-associated markers (ii) embryoid body-based differentiation into cell types representative of the three germ layers and (iii) the similarity between the transcriptome of the iPSC line and the human embryonic stem cell line H1 with a Pearson correlation of 0...
March 20, 2018: Stem Cell Research
https://www.readbyqxmd.com/read/29552298/synergistic-neuroprotective-effect-of-rasagiline-and-idebenone-against-retinal-ischemia-reperfusion-injury-via-the-lin28-let-7-dicer-pathway
#14
Dawei Lei, Zhengbo Shao, Xinrong Zhou, Huiping Yuan
Retinal ischemia-reperfusion (RIR) injury causes neuronal degeneration and initiates various optic nerve diseases. This study aimed to investigate the synergistic neuroprotective effect of rasagiline and idebenone against RIR injury. A combination of rasagiline and idebenone was administered intraperitoneally immediately after establishment of the RIR model. Treatment with the combination of the two drugs resulted in a significant restoration of retinal thickness and retinal ganglion cells. Apoptosis of cells in ganglion cell layers was also ameliorated, suggesting that the effect of the two drugs was synergistic and the expression of brain-derived neurotrophic factor increased...
February 23, 2018: Oncotarget
https://www.readbyqxmd.com/read/29540527/a-biosensor-for-mapk-dependent-lin28-signaling
#15
Laurel M Oldach, Kirill Gorshkov, William T Mills, Jin Zhang, Mollie K Meffert
Intracellular levels of the RNA-binding protein and pluripotency factor, Lin28a, are tightly controlled to govern cellular and organismal growth. Lin28a is extensively regulated at the posttranscriptional level, and can undergo mitogen-activated protein kinase (MAPK)-mediated elevation from low basal levels in differentiated cells by phosphorylation-dependent stabilizing interaction with the RNA-silencing factor HIV TAR RNA-binding protein (TRBP). However, molecular and spatiotemporal details of this critical control mechanism remained unknown...
May 15, 2018: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/29510730/the-lncrna-macc1-as1-promotes-gastric-cancer-cell-metabolic-plasticity-via-ampk-lin28-mediated-mrna-stability-of-macc1
#16
Yang Zhao, Yajing Liu, Li Lin, Qiong Huang, Wanming He, Shuyi Zhang, Shumin Dong, Zhaowei Wen, Jinjun Rao, Wangjun Liao, Min Shi
BACKGROUND: Metabolic plasticity has been increasingly thought to be a determinant of tumor growth and metastasis. MACC1, a transcriptional regulator of MET, was recognized as an oncogene in gastric cancer (GC); however, its transcriptional or post-translational regulation was not clear. We previously reported the metabolic role of MACC1 in glycolysis to promote GC progression. MACC1-AS1 is the antisense lncRNA of MACC1, yet its function was previously unknown. METHODS: We profiled and analyzed the expression of MACC1-AS1 utilizing the TCGA database as well as in situ hybridization using 123 pairs of GC tissues and matched adjacent normal gastric mucosa tissues (ANTs)...
March 6, 2018: Molecular Cancer
https://www.readbyqxmd.com/read/29499498/generation-of-a-human-ipsc-line-by-mrna-reprogramming
#17
Ana Artero Castro, Marian León, Verónica Del Buey Furió, Slaven Erceg, Dunja Lukovic
The human iPSC cell line, derived from foreskin fibroblasts was generated by non-integrative, non-viral reprogramming technology using OCT4, SOX2, KLF4, LIN28, c-MYC mRNAs.
April 2018: Stem Cell Research
https://www.readbyqxmd.com/read/29487310/immunologic-targeting-of-cd30-eliminates-tumourigenic-human-pluripotent-stem-cells-allowing-safer-clinical-application-of-hipsc-based-cell-therapy
#18
Nagako Sougawa, Shigeru Miyagawa, Satsuki Fukushima, Ai Kawamura, Junya Yokoyama, Emiko Ito, Akima Harada, Kaori Okimoto, Noriko Mochizuki-Oda, Atsuhiro Saito, Yoshiki Sawa
Induced pluripotent stem cells (iPSCs) are promising candidate cells for cardiomyogenesis in the failing heart. However, teratoma/tumour formation originating from undifferentiated iPSCs contaminating the graft is a critical concern for clinical application. Here, we hypothesized that brentuximab vedotin, which targets CD30, induces apoptosis in tumourigenic cells, thus increasing the safety of iPSC therapy for heart failure. Flow cytometry analysis identified consistent expression of CD30 in undifferentiated human iPSCs...
February 27, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29462197/thymic-epithelial-cell-derived-signals-control-b-progenitor-formation-and-proliferation-in-the-thymus-by-regulating-let-7-and-arid3a
#19
Shiyun Xiao, Wen Zhang, Nancy R Manley
The postnatal thymus is an efficient microenvironment for T cell specification and differentiation. B cells are also present in the thymus and have been recently shown to impact T cell selection, however, the mechanisms controlling B cell development in the thymus are largely unknown. In Foxn1lacZ mutant mice, down-regulation of Foxn1 expression in thymic epithelial cells beginning 1 week after birth caused a dramatic reduction of T progenitors and an increase of B cell progenitors. This time point is coincident with the switch from fetal to adult-type hematopoietic stem cells (HSCs), which is regulated by the Lin28-Let7 system...
2018: PloS One
https://www.readbyqxmd.com/read/29423528/cellular-functions-of-stem-cell-factors-mediated-by-the-ubiquitin-proteasome-system
#20
REVIEW
Jihye Choi, Kwang-Hyun Baek
Stem cells undergo partitioning through mitosis and separate into specific cells of each of the three embryonic germ layers: endoderm, mesoderm, and ectoderm. Pluripotency, reprogramming, and self-renewal are essential elements of embryonic stem cells (ESCs), and it is becoming evident that regulation of protein degradation mediated by the ubiquitin-proteasome system (UPS) is one of the key cellular mechanisms in ESCs. Although the framework of that mechanism may seem simple, it involves complicated proteolytic machinery...
June 2018: Cellular and Molecular Life Sciences: CMLS
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