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https://www.readbyqxmd.com/read/29541383/e3-ubiquitin-ligase-tripartite-motif-containing-71-promotes-the-proliferation-of-non-small-cell-lung-cancer-through-the-inhibitor-of-kappab-%C3%AE-nuclear-factor-kappab-pathway
#1
Hongjiu Ren, Yitong Xu, Qiongzi Wang, Jun Jiang, Wudumuli, Linping Hui, Qingfu Zhang, Xiupeng Zhang, Enhua Wang, Limei Sun, Xueshan Qiu
Tripartite motif-containing (TRIM) 71 belongs to the TRIM protein family. Many studies have shown that TRIM71 plays conserved roles in stem cell proliferation, differentiation, and embryonic development; however, the relationship between TRIM71 and tumorigenesis is not clear. In this study, we demonstrate that TRIM71 expression in non-small cell lung cancer (NSCLC) is associated with tumor size, lymph node metastasis, TNM stage, and poor prognosis. We found that TRIM71 was highly expressed in NSCLC cell lines compared with that in human normal bronchial epithelial cells...
February 16, 2018: Oncotarget
https://www.readbyqxmd.com/read/29434669/copy-number-variation-and-regions-of-homozygosity-analysis-in-patients-with-m%C3%A3-llerian-aplasia
#2
Durkadin Demir Eksi, Yiping Shen, Munire Erman, Lynn P Chorich, Megan E Sullivan, Meric Bilekdemir, Elanur Yılmaz, Guven Luleci, Hyung-Goo Kim, Ozgul M Alper, Lawrence C Layman
Background: Little is known about the genetic contribution to Müllerian aplasia, better known to patients as Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome. Mutations in two genes (WNT4 and HNF1B) account for a small number of patients, but heterozygous copy number variants (CNVs) have been described. However, the significance of these CNVs in the pathogenesis of MRKH is unknown, but suggests possible autosomal dominant inheritance. We are not aware of CNV studies in consanguineous patients, which could pinpoint genes important in autosomal recessive MRKH...
2018: Molecular Cytogenetics
https://www.readbyqxmd.com/read/29216221/copy-number-variants-in-ebstein-anomaly
#3
Andreas Giannakou, Robert J Sicko, Wei Zhang, Paul Romitti, Marilyn L Browne, Michele Caggana, Lawrence C Brody, Laura Jelliffe-Pawlowski, Gary M Shaw, Denise M Kay, James L Mills
BACKGROUND: Ebstein anomaly (EA) is a rare congenital defect characterized by apical displacement of the septal tricuspid leaflets and atrialization of the right ventricle. The etiology of EA is unclear; however, recurrence in families and the association of EA with genetic syndromes and copy number variants (CNVs) suggest a genetic component. OBJECTIVE: We performed a population-based study to search for recurrent and novel CNVs in a previously unreported set of EA cases...
2017: PloS One
https://www.readbyqxmd.com/read/28723672/e3-ubiquitin-ligase-tripartite-motif-containing-71-promotes-the-proliferation-of-non-small-cell-lung-cancer-through-the-inhibitor-of-kappab-%C3%AE-nuclear-factor-kappab-pathway
#4
Hongjiu Ren, Yitong Xu, Qiongzi Wang, Jun Jiang, Wudumuli, Linping Hui, Qingfu Zhang, Xiupeng Zhang, Enhua Wang, Limei Sun, Xueshan Qiu
Tripartite motif-containing (TRIM) 71 belongs to the TRIM protein family. Many studies have shown that TRIM71 plays conserved roles in stem cell proliferation, differentiation, and embryonic development; however, the relationship between TRIM71 and tumorigenesis is not clear. In this study, we demonstrate that TRIM71 expression in non-small cell lung cancer (NSCLC) is associated with tumor size, lymph node metastasis, TNM stage, and poor prognosis. We found that TRIM71 was highly expressed in NSCLC cell lines compared with that in human normal bronchial epithelial cells...
July 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28431233/a-compendium-of-rna-binding-proteins-that-regulate-microrna-biogenesis
#5
Thomas Treiber, Nora Treiber, Uwe Plessmann, Simone Harlander, Julia-Lisa Daiß, Norbert Eichner, Gerhard Lehmann, Kevin Schall, Henning Urlaub, Gunter Meister
During microRNA (miRNA) biogenesis, two endonucleolytic reactions convert stem-loop-structured precursors into mature miRNAs. These processing steps can be posttranscriptionally regulated by RNA-binding proteins (RBPs). Here, we have used a proteomics-based pull-down approach to map and characterize the interactome of a multitude of pre-miRNAs. We identify ∼180 RBPs that interact specifically with distinct pre-miRNAs. For functional validation, we combined RNAi and CRISPR/Cas-mediated knockout experiments to analyze RBP-dependent changes in miRNA levels...
April 20, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28430184/the-ubiquitin-ligase-lin41-trim71-targets-p53-to-antagonize-cell-death-and-differentiation-pathways-during-stem-cell-differentiation
#6
Duong Thi Thuy Nguyen, Daniel Richter, Geert Michel, Sibylle Mitschka, Waldemar Kolanus, Elisa Cuevas, F Gregory Wulczyn
Rapidity and specificity are characteristic features of proteolysis mediated by the ubiquitin-proteasome system. Therefore, the UPS is ideally suited for the remodeling of the embryonic stem cell proteome during the transition from pluripotent to differentiated states and its inverse, the generation of inducible pluripotent stem cells. The Trim-NHL family member LIN41 is among the first E3 ubiquitin ligases to be linked to stem cell pluripotency and reprogramming. Initially discovered in C. elegans as a downstream target of the let-7 miRNA, LIN41 is now recognized as a critical regulator of stem cell fates as well as the timing of neurogenesis...
June 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28111013/lin41-post-transcriptionally-silences-mrnas-by-two-distinct-and-position-dependent-mechanisms
#7
Florian Aeschimann, Pooja Kumari, Hrishikesh Bartake, Dimos Gaidatzis, Lan Xu, Rafal Ciosk, Helge Großhans
The RNA-binding protein (RBP) LIN41, also known as LIN-41 or TRIM71, is a key regulator of animal development, but its physiological targets and molecular mechanism of action are largely elusive. Here we find that this RBP has two distinct mRNA-silencing activities. Using genome-wide ribosome profiling, RNA immunoprecipitation, and in vitro-binding experiments, we identify four mRNAs, each encoding a transcription factor or cofactor, as direct physiological targets of C. elegans LIN41. LIN41 silences three of these targets through their 3' UTRs, but it achieves isoform-specific silencing of one target, lin-29A, through its unique 5' UTR...
February 2, 2017: Molecular Cell
https://www.readbyqxmd.com/read/27821801/trim71-suppresses-tumorigenesis-via-modulation-of-lin28b-let-7-hmga2-signaling
#8
Jinlong Yin, Tae-Hoon Kim, Nayun Park, Daye Shin, Hae In Choi, Sungchan Cho, Jong Bae Park, Jong Heon Kim
TRIM71 (tripartite motif-containing 71) belongs to the TRIM-NHL protein family, which plays a conserved role in regulating early development and differentiation. However, the molecular functions of TRIM71 have remained largely unknown. Here, we explored the role of TRIM71 together with modulation of Lin28B-let-7-HMGA2 (high-mobility group AT-hook 2) signaling in tumorigenesis. TRIM71 overexpression opposed Lin28B-induced transformation in primary cells and inhibited tumor formation in a mouse model. Specific knockdown of TRIM71 expression increased cancer cell proliferation and invasion...
November 29, 2016: Oncotarget
https://www.readbyqxmd.com/read/27534418/late-maternal-folate-supplementation-rescues-from-methyl-donor-deficiency-associated-brain-defects-by-restoring-let-7-and-mir-34-pathways
#9
Andréa Geoffroy, Racha Kerek, Grégory Pourié, Déborah Helle, Jean-Louis Guéant, Jean-Luc Daval, Carine Bossenmeyer-Pourié
The micronutrients folate and vitamin B12 are essential for the proper development of the central nervous system, and their deficiency during pregnancy has been associated with a wide range of disorders. They act as methyl donors in the one-carbon metabolism which critically influences epigenetic mechanisms. In order to depict further underlying mechanisms, we investigated the role of let-7 and miR-34, two microRNAs regulated by methylation, on a rat model of maternal deficiency. In several countries, public health policies recommend periconceptional supplementation with folic acid...
September 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/27478502/a-balanced-chromosomal-translocation-involving-chromosomes-3-and-16-in-a-patient-with-mayer-rokitansky-kuster-hauser-syndrome-reveals-new-candidate-genes-at-3p22-3-and-16p13-3
#10
Lacey S Williams, Hyung-Goo Kim, Vera M Kalscheuer, J Matthew Tuck, Lynn P Chorich, Megan E Sullivan, Allison Falkenstrom, Richard H Reindollar, Lawrence C Layman
BACKGROUND: Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome, or the congenital absence of uterus and vagina, is the most severe anomaly of the female reproductive tract. It affects 1 in 5,000 females, and is the second most common cause of primary amenorrhea. The etiology remains unknown in most patients, although four single gene defects and some repetitive copy number variants (CNVs) have been identified. Translocations in MRKH patients are very rare, and reported only in three patients previously without breakpoint mapping...
2016: Molecular Cytogenetics
https://www.readbyqxmd.com/read/27300003/folate-receptor-alpha-upregulates-oct4-sox2-and-klf4-and-downregulates-mir-138-and-mir-let-7-in-cranial-neural-crest-cells
#11
Vineet Mohanty, Amar Shah, Elise Allender, M Rizwan Siddiqui, Sarah Monick, Shunsuke Ichi, Barbara Mania-Farnell, David G McLone, Tadanori Tomita, Chandra Shekhar Mayanil
Prenatal folic acid (FA) supplementation prevents neural tube defects. Folate receptor alpha (FRα) is critical for embryonic development, including neural crest (NC) development. Previously we showed that FRα translocates to the nucleus in response to FA, where it acts as a transcription factor. In this study, we examined if FA through interaction with FRα regulates stem cell characteristics of cranial neural crest cells (CNCCs)-critical for normal development. We hypothesized that FRα upregulates coding genes and simultaneously downregulates non-coding miRNA which targets coding genes in CNCCs...
November 2016: Stem Cells
https://www.readbyqxmd.com/read/26764022/pateamine-a-sensitive-ribosome-profiling-reveals-the-scope-of-translation-in-mouse-embryonic-stem-cells
#12
Alexandra Popa, Kevin Lebrigand, Pascal Barbry, Rainer Waldmann
BACKGROUND: Open reading frames are common in long noncoding RNAs (lncRNAs) and 5'UTRs of protein coding transcripts (uORFs). The question of whether those ORFs are translated was recently addressed by several groups using ribosome profiling. Most of those studies concluded that certain lncRNAs and uORFs are translated, essentially based on computational analysis of ribosome footprints. However, major discrepancies remain on the scope of translation and the translational status of individual ORFs...
2016: BMC Genomics
https://www.readbyqxmd.com/read/26057209/co-existence-of-intact-stemness-and-priming-of-neural-differentiation-programs-in-mes-cells-lacking-trim71
#13
Sibylle Mitschka, Thomas Ulas, Tobias Goller, Karin Schneider, Angela Egert, Jérôme Mertens, Oliver Brüstle, Hubert Schorle, Marc Beyer, Kathrin Klee, Jia Xue, Patrick Günther, Kevin Bassler, Joachim L Schultze, Waldemar Kolanus
Regulatory networks for differentiation and pluripotency in embryonic stem (ES) cells have long been suggested to be mutually exclusive. However, with the identification of many new components of these networks ranging from epigenetic, transcriptional, and translational to even post-translational mechanisms, the cellular states of pluripotency and early differentiation might not be strictly bi-modal, but differentiating stem cells appear to go through phases of simultaneous expression of stemness and differentiation genes...
2015: Scientific Reports
https://www.readbyqxmd.com/read/25996682/identification-of-differentially-methylated-markers-among-cytogenetic-risk-groups-of-acute-myeloid-leukemia
#14
Xiaoyu Qu, Jerry Davison, Liping Du, Barry Storer, Derek L Stirewalt, Shelly Heimfeld, Elihu Estey, Frederick R Appelbaum, Min Fang
Aberrant DNA methylation is known to occur in cancer, including hematological malignancies such as acute myeloid leukemia (AML). However, less is known about whether specific methylation profiles characterize specific subcategories of AML. We examined this issue by using comprehensive high-throughput array-based relative methylation analysis (CHARM) to compare methylation profiles among patients in different AML cytogenetic risk groups. We found distinct profiles in each group, with the high-risk group showing overall increased methylation compared with low- and mid-risk groups...
2015: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/25883935/lin41-trim71-is-essential-for-mouse-development-and-specifically-expressed-in-postnatal-ependymal-cells-of-the-brain
#15
Elisa Cuevas, Agnieszka Rybak-Wolf, Anna M Rohde, Duong T T Nguyen, F Gregory Wulczyn
Lin41/Trim71 is a heterochronic gene encoding a member of the Trim-NHL protein family, and is the original, genetically defined target of the microRNA let-7 in C. elegans. Both the LIN41 protein and multiple regulatory microRNA binding sites in the 3' UTR of the mRNA are highly conserved from nematodes to humans. Functional studies have described essential roles for mouse LIN41 in embryonic stem cells, cellular reprogramming and the timing of embryonic neurogenesis. We have used a new gene trap mouse line deficient in Lin41 to characterize Lin41 expression during embryonic development and in the postnatal central nervous system (CNS)...
2015: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/25669883/the-let-7-microrna-directs-vulval-development-through-a-single-target
#16
Matyas Ecsedi, Magdalene Rausch, Helge Großhans
The let-7 microRNA (miRNA) regulates stemness in animals ranging from worms to humans. However, the cause of the dramatic vulval rupturing phenotype of let-7 mutant C. elegans has remained unknown. Consistent with the notion that miRNAs function by coordinately tuning the expression of many targets, bursting may result from joint dysregulation of several targets, possibly in the epidermis. Alternatively, overexpression of LET-60/RAS, a key vulva development gene and a phylogenetically conserved target of let-7, may be responsible...
February 9, 2015: Developmental Cell
https://www.readbyqxmd.com/read/25115389/identification-of-a-gene-expression-driven-progression-pathway-in-myxoid-liposarcoma
#17
Loris De Cecco, Tiziana Negri, Silvia Brich, Valentina Mauro, Fabio Bozzi, GianPaolo Dagrada, Vittoria Disciglio, Roberta Sanfilippo, Alessandro Gronchi, Maurizio D'Incalci, Paolo G Casali, Silvana Canevari, Marco A Pierotti, Silvana Pilotti
to investigate the events involved in the progression of myxoid liposarcoma (MLS). Gene expression profiling and immunohistochemical/biochemical analyses were applied to specimens representative of the opposite ends of the MLS spectrum: pure myxoid (ML) and pure round cell (RC) liposarcomas. The analyses revealed the involvement of both coding and non coding RNAs (SNORDs located in DLK1-DIO3 region) and support a model of stepwise progression mainly driven by epigenetic changes involving tumour vascular supply and tumoral cellular component...
August 15, 2014: Oncotarget
https://www.readbyqxmd.com/read/24731722/dna-methylation-study-of-fetus-genome-through-a-genome-wide-analysis
#18
Hong-Dan Wang, Qiao-Fang Hou, Qian-Nan Guo, Tao Li, Dong Wu, Xian-Ping Zhang, Yan Chu, Miao He, Hai Xiao, Liang-Jie Guo, Ke Yang, Shi-Xiu Liao, Bo-Feng Zhu
BACKGROUND: DNA methylation is a crucial epigenetic modification of the genome which is involved in embryonic development, transcription, chromatin structure, X chromosome inactivation, genomic imprinting and chromosome stability. Consistent with these important roles, DNA methylation has been demonstrated to be required for vertebrate early embryogenesis and essential for regulating temporal and spatial expression of genes controlling cell fate and differentiation. Further studies have shown that abnormal DNA methylation is associated with human diseases including the embryonic development diseases...
2014: BMC Medical Genomics
https://www.readbyqxmd.com/read/24602972/the-ubiquitin-ligase-human-trim71-regulates-let-7-microrna-biogenesis-via-modulation-of-lin28b-protein
#19
Seo Hyun Lee, Sungchan Cho, M Sun Kim, Kwangman Choi, Jae Youl Cho, Ho-Shin Gwak, Youn-Jae Kim, Heon Yoo, Seung-Hoon Lee, Jong Bae Park, Jong Heon Kim
let-7 microRNA (miRNA) is implicated in various biological processes, and its downregulation essentially linked to human malignancy. Regulation of gene expression of the let-7 family is critically linked to RNA-binding proteins. For instance, Lin28B and its paralog, Lin28A, inhibit the pre-let-7 precursor from being processed to mature miRNA by recruiting terminal uridyltransferase, TUT4, which adds oligomeric U at the 3' end, suggesting that deregulation of Lin28B, together with Lin28A, may alter various biological processes through modulation of let-7 expression...
May 2014: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/24239284/the-let-7-lin-41-pathway-regulates-reprogramming-to-human-induced-pluripotent-stem-cells-by-controlling-expression-of-prodifferentiation-genes
#20
Kathleen A Worringer, Tim A Rand, Yohei Hayashi, Salma Sami, Kazutoshi Takahashi, Koji Tanabe, Megumi Narita, Deepak Srivastava, Shinya Yamanaka
Reprogramming differentiated cells into induced pluripotent stem cells (iPSCs) promotes a broad array of cellular changes. Here we show that the let-7 family of microRNAs acts as an inhibitory influence on the reprogramming process through a regulatory pathway involving prodifferentiation factors, including EGR1. Inhibiting let-7 in human cells promotes reprogramming to a comparable extent to c-MYC when combined with OCT4, SOX2, and KLF4, and persistence of let-7 inhibits reprogramming. Inhibiting let-7 during reprogramming leads to an increase in the level of the let-7 target LIN-41/TRIM71, which in turn promotes reprogramming and is important for overcoming the let-7 barrier to reprogramming...
January 2, 2014: Cell Stem Cell
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