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https://www.readbyqxmd.com/read/29563491/rna-cytosine-methylation-and-methyltransferases-mediate-chromatin-organization-and-5-azacytidine-response-and-resistance-in-leukaemia
#1
Jason X Cheng, Li Chen, Yuan Li, Adam Cloe, Ming Yue, Jiangbo Wei, Kenneth A Watanabe, Jamile M Shammo, John Anastasi, Qingxi J Shen, Richard A Larson, Chuan He, Michelle M Le Beau, James W Vardiman
The roles of RNA 5-methylcytosine (RNA:m5 C) and RNA:m5 C methyltransferases (RCMTs) in lineage-associated chromatin organization and drug response/resistance are unclear. Here we demonstrate that the RCMTs, namely NSUN3 and DNMT2, directly bind hnRNPK, a conserved RNA-binding protein. hnRNPK interacts with the lineage-determining transcription factors (TFs), GATA1 and SPI1/PU.1, and with CDK9/P-TEFb to recruit RNA-polymerase-II at nascent RNA, leading to formation of 5-Azacitidine (5-AZA)-sensitive chromatin structure...
March 21, 2018: Nature Communications
https://www.readbyqxmd.com/read/29491376/pan-cancer-analysis-of-s-phase-enriched-lncrnas-identifies-oncogenic-drivers-and-biomarkers
#2
Mohamad Moustafa Ali, Vijay Suresh Akhade, Subazini Thankaswamy Kosalai, Santhilal Subhash, Luisa Statello, Matthieu Meryet-Figuiere, Jonas Abrahamsson, Tanmoy Mondal, Chandrasekhar Kanduri
Despite improvement in our understanding of long noncoding RNAs (lncRNAs) role in cancer, efforts to find clinically relevant cancer-associated lncRNAs are still lacking. Here, using nascent RNA capture sequencing, we identify 1145 temporally expressed S-phase-enriched lncRNAs. Among these, 570 lncRNAs show significant differential expression in at least one tumor type across TCGA data sets. Systematic clinical investigation of 14 Pan-Cancer data sets identified 633 independent prognostic markers. Silencing of the top differentially expressed and clinically relevant S-phase-enriched lncRNAs in several cancer models affects crucial cancer cell hallmarks...
February 28, 2018: Nature Communications
https://www.readbyqxmd.com/read/29466324/sequences-enriched-in-alu-repeats-drive-nuclear-localization-of-long-rnas-in-human-cells
#3
Yoav Lubelsky, Igor Ulitsky
Long noncoding RNAs (lncRNAs) are emerging as key players in multiple cellular pathways1 , but their modes of action and how those are dictated by sequence remain unclear. lncRNAs tend to be enriched in the nuclear fraction, whereas most mRNAs are overtly cytoplasmic2 , although several studies have found that hundreds of mRNAs in various cell types are retained in the nucleus3,4 . It is thus conceivable that some mechanisms that promote nuclear enrichment are shared between lncRNAs and mRNAs. In order to identify elements that can force nuclear localization in lncRNAs and mRNAs we screened libraries of short fragments tiled across nuclear RNAs, which were cloned into the untranslated regions of an efficiently exported mRNA...
January 24, 2018: Nature
https://www.readbyqxmd.com/read/29410604/exosomal-lncrna-91h-is-associated-with-poor-development-in-colorectal-cancer-by-modifying-hnrnpk-expression
#4
Tianyi Gao, Xiangxiang Liu, Bangshun He, Zhenlin Nie, Chengbin Zhu, Pei Zhang, Shukui Wang
Background: Exosomes mediated transfer of lncRNA 91H may play a critical role in the development of CRC. However, few studies have proved the mechanism. So we performed this study to deeply explore the biological functions of exosomal 91H in the development and progression of CRC. Methods: The association between lncRNA 91H and exosomes was detected in vitro and vivo. Then RNA pulldown and RIP were used to detect how lncRNA 91H affect CRC IGF2 express. At last, clinic pathological significance of exosomal 91H was evaluated by Cox proportional hazards model...
2018: Cancer Cell International
https://www.readbyqxmd.com/read/29311158/long-noncoding-rna-pancets-1-promotes-neuroblastoma-progression-through-hnrnpk-mediated-%C3%AE-catenin-stabilization
#5
Dan Li, Xiaojing Wang, Hong Mei, Erhu Fang, Lin Ye, Huajie Song, Feng Yang, Huanhuan Li, Kai Huang, Liduan Zheng, Qiangsong Tong
Long noncoding RNAs (lncRNAs) play essential roles in tumor progression. However, the functions of lncRNAs in the tumorigenesis and aggressiveness of neuroblastoma (NB) still remain to be determined. Here, we report the identification of lncRNA pancEts-1 as a novel driver of NB progression by using a public microarray dataset. LncRNA pancEts-1 promoted the growth, invasion, and metastasis of NB cells in vitro and in vivo. Mechanistically, pancEts-1 bound to hnRNPK to facilitate its physical interaction with β-catenin, while hnRNPK stabilized the β-catenin by inhibiting proteasome-mediated degradation, resulting in transcriptional alteration of target genes associated with NB progression...
January 8, 2018: Cancer Research
https://www.readbyqxmd.com/read/29220657/hnrnpk-recruits-pcgf3-5-prc1-to-the-xist-rna-b-repeat-to-establish-polycomb-mediated-chromosomal-silencing
#6
Greta Pintacuda, Guifeng Wei, Chloë Roustan, Burcu Anil Kirmizitas, Nicolae Solcan, Andrea Cerase, Alfredo Castello, Shabaz Mohammed, Benoît Moindrot, Tatyana B Nesterova, Neil Brockdorff
The Polycomb-repressive complexes PRC1 and PRC2 play a key role in chromosome silencing induced by the non-coding RNA Xist. Polycomb recruitment is initiated by the PCGF3/5-PRC1 complex, which catalyzes chromosome-wide H2A lysine 119 ubiquitylation, signaling recruitment of other PRC1 complexes, and PRC2. However, the molecular mechanism for PCGF3/5-PRC1 recruitment by Xist RNA is not understood. Here we define the Xist RNA Polycomb Interaction Domain (XR-PID), a 600 nt sequence encompassing the Xist B-repeat element...
December 7, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28976774/proteomic-analysis-of-extracellular-hmgb1-identifies-binding-partners-and-exposes-its-potential-role-in-airway-epithelial-cell-homeostasis
#7
Sharon L Wong, Joyce To, Jerran Santos, Venkata Sita Rama Raju Allam, John P Dalton, Steven P Djordjevic, Sheila Donnelly, Matthew P Padula, Maria B Sukkar
The release of damage-associated molecular patterns (DAMPs) by airway epithelial cells is believed to play a crucial role in the initiation and development of chronic airway conditions such as asthma and chronic obstructive pulmonary disease (COPD). Intriguingly, the classic DAMP high-mobility group box-1 (HMGB1) is detected in the culture supernatant of airway epithelial cells under basal conditions, indicating a role for HMGB1 in the regulation of epithelial cellular and immune homeostasis. To gain contextual insight into the potential role of HMGB1 in airway epithelial cell homeostasis, we used the orthogonal and complementary methods of high-resolution clear native electrophoresis, immunoprecipitation, and pull-downs coupled to liquid chromatography-tandem mass spectrometry (LC-MS/MS) to profile HMGB1 and its binding partners in the culture supernatant of unstimulated airway epithelial cells...
January 5, 2018: Journal of Proteome Research
https://www.readbyqxmd.com/read/28932298/expression-of-hnrnpk-claudin-4-in-hcv-induced-early-hcc-and-adjacent-liver-tissue
#8
Olfat Hammam, Mona Magdy, Amgad Anas, Ali Abdel Rahim, Mohamed Heedaya, Ahmed Helmy
BACKGROUND: HCC in Egypt usually occurs in HCV cirrhotic livers with poor prognosis due to late diagnosis. High hnRNPK & low Claudin-4 profiles indicate Epithelial Mesenchymal Transition (EMT), malignant transformation and high-grade tumours. AIM: We studied the immunohistochemical expression of hnRNPK and Claudin-4 in HCV induced early HCC (eHCC) and adjacent liver tissue in Egyptian patients to improve eHCC detection in cirrhotic livers with better curative therapy options...
August 15, 2017: Open Access Macedonian Journal of Medical Sciences
https://www.readbyqxmd.com/read/28869607/mrpl33-and-its-splicing-regulator-hnrnpk-are-required-for-mitochondria-function-and-implicated-in-tumor-progression
#9
L Liu, C Luo, Y Luo, L Chen, Y Liu, Y Wang, J Han, Y Zhang, N Wei, Z Xie, W Wu, G Wu, Y Feng
MRPL33 gene encodes a large mitoribosomal subunit protein, which may be involved in mitochondrial translation. Although two splice variants of MRPL33 have been described, its splicing regulation remains elusive. Here we observed that inclusion of alternative exon 3 was greatly promoted in a panel of human cancer cells. Depletion of the exon 3-containing long isoform of MRPL33 (MRPL33-L) led to impaired proliferation and increased apoptosis in cancer cell lines and in a xenograft model. MRPL33-L knockdown could also induce mitochondrial dysfunction including increased accumulation of reactive oxygen species, decreased ATP production and 16 S rRNA levels...
January 4, 2018: Oncogene
https://www.readbyqxmd.com/read/28783126/the-neuroprotective-marine-compound-psammaplysene-a-binds-the-rna-binding-protein-hnrnpk
#10
Marco Boccitto, Nayoung Lee, Satoshi Sakamoto, Lynn A Spruce, Hiroshi Handa, Jon Clardy, Steven H Seeholzer, Robert G Kalb
In previous work, we characterized the strong neuroprotective properties of the marine compound Psammaplysene A (PA) in in vitro and in vivo models of neurodegeneration. Based on its strong neuroprotective activity, the current work attempts to identify the physical target of PA to gain mechanistic insight into its molecular action. Two distinct methods, used in parallel, to purify protein-binding partners of PA led to the identification of HNRNPK as a direct target of PA. Based on surface plasmon resonance, we find that the binding of PA to HNRNPK is RNA-dependent...
August 7, 2017: Marine Drugs
https://www.readbyqxmd.com/read/28758620/antibodies-against-the-mono-methylated-arginine-glycine-repeat-mma-rg-of-the-epstein-barr-virus-nuclear-antigen-2-ebna2-identify-potential-cellular-proteins-targeted-in-viral-transformation
#11
Hiresh Ayoubian, Thomas Fröhlich, Dagmar Pogodski, Andrew Flatley, Elisabeth Kremmer, Aloys Schepers, Regina Feederle, Georg J Arnold, Friedrich A Grässer
The Epstein-Barr virus is a human herpes virus with oncogenic potential. The virus-encoded nuclear antigen 2 (EBNA2) is a key mediator of viral tumorigenesis. EBNA2 features an arginine-glycine (RG) repeat at amino acids (aa)339-354 that is essential for the transformation of lymphocytes and contains symmetrically (SDMA) and asymmetrically (ADMA) di-methylated arginine residues. The SDMA-modified EBNA2 binds the survival motor neuron protein (SMN), thus mimicking SMD3, a cellular SDMA-containing protein that interacts with SMN...
August 2017: Journal of General Virology
https://www.readbyqxmd.com/read/28756806/erk1-2-mediated-cytoplasmic-accumulation-of-hnrnpk-antagonizes-trail-induced-apoptosis-through-upregulation-of-xiap-in-h1299-cells
#12
Wen Si Huang, Feng Mei Xu, Qing Zhong Zeng, Xiao Hui Liu, Xue Juan Gao, Lang Xia Liu
OBJECTIVE: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) resistance greatly limits the clinical therapeutic efficacy of TRAIL. Elucidating the molecular mechanism underlying TRAIL resistance will be fundamental to resolving this problem. METHODS: Nuclear and cytoplasmic protein extraction and immuno?uorescence (IF) assay were used to detect changes in heterogeneous nuclear ribonucleoprotein K (hnRNPK) localization in H1299 cells. The evaluation of cell apoptosis in cells transfected with GFP-hnRNPK, GFP-hnRNPK S284/353A, or GFP-hnRNPK S284/353D mutant was performed using cleaved caspase-3 antibody...
July 2017: Biomedical and Environmental Sciences: BES
https://www.readbyqxmd.com/read/28735747/a-requirement-for-mena-an-actin-regulator-in-local-mrna-translation-in-developing-neurons
#13
Marina Vidaki, Frauke Drees, Tanvi Saxena, Erwin Lanslots, Matthew J Taliaferro, Antonios Tatarakis, Christopher B Burge, Eric T Wang, Frank B Gertler
During neuronal development, local mRNA translation is required for axon guidance and synaptogenesis, and dysregulation of this process contributes to multiple neurodevelopmental and cognitive disorders. However, regulation of local protein synthesis in developing axons remains poorly understood. Here, we uncover a novel role for the actin-regulatory protein Mena in the formation of a ribonucleoprotein complex that involves the RNA-binding proteins HnrnpK and PCBP1 and regulates local translation of specific mRNAs in developing axons...
August 2, 2017: Neuron
https://www.readbyqxmd.com/read/28708135/regulation-of-plk1-through-competition-between-hnrnpk-mir-149-3p-and-mir-193b-5p
#14
Chang Hoon Shin, Hong Lee, Hye Ree Kim, Kyung Hee Choi, Je-Gun Joung, Hyeon Ho Kim
Polo-like kinase 1 (PLK1) is a critical regulator of cell cycle progression and apoptosis. However, its regulation remains poorly understood. In the present study, we investigated the molecular mechanism underlying the post-transcriptional regulation of PLK1. We observed that heterogeneous nuclear ribonucleoprotein K (hnRNPK) and PLK1 were positively associated in several different cancers and high expression levels of them correlated with poor prognosis in patients with cancer. Knockdown of hnRNPK resulted in reduced expression of PLK1, whereas conversely, PLK1 expression was increased in hnRNPK-overexpressing cells...
November 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28555196/exogenous-expressions-of-fto-wild-type-and-r316q-mutant-proteins-caused-an-increase-in-hnrpk-levels-in-3t3-l1-cells-as-demonstrated-by-dige-analysis
#15
Nil Guzel, Murat Kasap, Aylin Kanli, Gurler Akpinar, M Dogan Gulkac, Kubra Karaosmanoglu
Fat mass and obesity-associated protein is an enzyme that oxidatively demethylates DNA. Although there are numerous studies regarding the catalytic function of FTO, the overall existence or absence of FTO on cellular proteome has not been investigated. This study investigated the changes in the soluble proteome of 3T3-L1 cells upon expression of the WT and the mutant (R316Q) FTO proteins. Protein extracts prepared from 3T3-L1 cells expressing either the WT or the mutant FTO proteins were used in DIGE experiments...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28426877/knockdown-of-hnrnpk-leads-to-increased-dna-damage-after-irradiation-and-reduces-survival-of-tumor-cells
#16
Nadine Wiesmann, Judith Strozynski, Carina Beck, Nadine Zimmermann, Simone Mendler, Rita Gieringer, Irene Schmidtmann, Jürgen Brieger
Radiotherapy is an important treatment option in the therapy of multiple tumor entities among them head and neck squamous cell carcinoma (HNSCC). However, the success of radiotherapy is limited by the development of radiation resistances. Heterogeneous nuclear ribonucleoprotein K (hnRNPK) is a cofactor of p53 and represents a potential target for radio sensitization of tumor cells. In this study, we analyzed the impact of hnRNPK on the DNA damage response after gamma irradiation. By yH2AX foci analysis, we found that hnRNPK knockdown increases DNA damage levels in irradiated cells...
March 1, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/28423633/novel-lincrna-slinky-is-a-prognostic-biomarker-in-kidney-cancer
#17
Xue Gong, Zurab Siprashvili, Okyaz Eminaga, Zhewei Shen, Yusuke Sato, Haruki Kume, Yukio Homma, Seishi Ogawa, Paul A Khavari, Jonathan R Pollack, James D Brooks
Clear cell renal cell carcinomas (ccRCC) show a broad range of clinical behavior, and prognostic biomarkers are needed to stratify patients for appropriate management. We sought to determine whether long intergenic non-coding RNAs (lincRNAs) might predict patient survival. Candidate prognostic lincRNAs were identified by mining The Cancer Genome Atlas (TCGA) transcriptome (RNA-seq) data on 466 ccRCC cases (randomized into discovery and validation sets) annotated for ~21,000 lncRNAs. A previously uncharacterized lincRNA, SLINKY (Survival-predictive LINcRNA in KidneY cancer), was the top-ranked prognostic lincRNA, and validated in an independent University of Tokyo cohort (P=0...
March 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423622/hnrnpk-mir-223-fbxw7-feedback-cascade-promotes-pancreatic-cancer-cell-growth-and-invasion
#18
D He, Cheng Huang, Qingxin Zhou, Dawei Liu, Longhui Xiong, Hongxia Xiang, Guangnian Ma, Zhiyong Zhang
Several studies have identified miR-223 critically involved in various types of cancer, including pancreatic ductal adenocarcinoma (PDAC). However, its action and regulatory mechanisms in PDAC remains largely unclear. In this study, we found that the expression levels of miR-223 were increased in clinical samples with PDAC (81.6%). The upregulation of miR-223 increases the proliferation, migration, and invasive abilities of PDAC cells in vitro and in vivo. Mechanistically, miR-223 directly targeted FBXW7 and overexpression of FBXW7 reverted miR-223- induced drastic proliferation in PDAC cells...
March 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28374925/clinical-spectrum-of-kabuki-like-syndrome-caused-by-hnrnpk-haploinsufficiency
#19
Maria Lisa Dentici, Sabina Barresi, Marcello Niceta, Francesca Pantaleoni, Simone Pizzi, Bruno Dallapiccola, Marco Tartaglia, Maria Cristina Digilio
Kabuki syndrome is a genetically heterogeneous disorder characterized by postnatal growth retardation, skeletal abnormalities, intellectual disability, facial dysmorphisms and a variable range of organ malformations. In ~30% of affected individuals, the underlying genetic defect remains unknown. A small number of inactivating heterozygous HNRNPK mutations has recently been reported to be associated with a condition partially overlapping or suggestive of Kabuki syndrome. Here, we report on an 11-year-old girl with a complex phenotype in whom the diagnosis of KS was suggested but molecular testing for the known causative disease genes was negative...
April 4, 2017: Clinical Genetics
https://www.readbyqxmd.com/read/28335083/down-regulation-of-dab2ip-promotes-colorectal-cancer-invasion-and-metastasis-by-translocating-hnrnpk-into-nucleus-to-enhance-the-transcription-of-mmp2
#20
X H Zhu, J M Wang, S S Yang, F F Wang, J L Hu, S N Xin, H Men, G F Lu, X L Lan, D Zhang, X Y Wang, W T Liao, Y Q Ding, L Liang
DOC-2/DAB2 interacting protein (DAB2IP) is a RasGAP protein that shows a suppressive effect on cancer progression. Our previous study showed the involvement of transcription regulation of DAB2IP in metastasis of colorectal cancer (CRC). However, the molecular mechanisms of DAB2IP in regulating the progression of CRC need to be further explored. Here, we identified heterogeneous nuclear ribonucleoprotein K (hnRNPK) and matrix metalloproteinase 2 (MMP2) as vital downstream targets of DAB2IP in CRC cells by two-dimensional fluorescence difference gel electrophoresis and cDNA microassay, respectively...
July 1, 2017: International Journal of Cancer. Journal International du Cancer
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