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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...
March 23, 2017: International Journal of Cancer. Journal International du Cancer
Mengmeng Xu, Long Che, Zhenguo Yang, Pan Zhang, Jiankai Shi, Jian Li, Yan Lin, Zhengfeng Fang, Lianqiang Che, Bin Feng, De Wu, Shengyu Xu
Primordial follicle formation represents a critical phase of the initiation of embryonic reproductive organ development, while the primordial follicle transition into primary follicle determines whether oestrus or ovulation will occur in female animals. To identify molecular mechanism of new proteins which are involved in ovarian development, we employed 2D-DIGE to compare the protein expression profiles of primordial follicles and primary follicles of fetal ovaries in pigs. Fetal ovaries were collected at distinct time-points of the gestation cycle (g55 and g90)...
2017: BioMed Research International
Chang Hoon Shin, Seongho Ryu, Hyeon Ho Kim
Antisense transcripts were initially identified as transcriptional noise, but have since been reported to play an important role in the quality control of miRNA functions. In this report, we tested the hypothesis that hnRNPK regulates miRNA function via competitive endogenous RNAs, such as pseudogenes, long non-coding RNAs, and antisense transcripts. Based on analyses of RNA sequencing data, the knockdown of hnRNPK decreased antisense PTOV1-AS1 transcript, which harbors five binding sites for miR-1207-5p. We identified heme oxygenase-1 (HO-1) mRNA as a novel target of miR-1207-5p by western blotting and Ago2 immunoprecipitation...
February 23, 2017: BMB Reports
Xu Chen, Peng Gu, Ruihui Xie, Jinli Han, Hao Liu, Bo Wang, Weibin Xie, Weijie Xie, Guangzheng Zhong, Changhao Chen, Shujie Xie, Ning Jiang, Tianxin Lin, Jian Huang
Heterogeneous nuclear ribonucleoprotein K (hnRNPK) is an essential RNA- and DNA-binding protein that regulates diverse biological events, especially DNA transcription. hnRNPK overexpression is related to tumorigenesis in several cancers. However, both the expression patterns and biological mechanisms of hnRNPK in bladder cancer are unclear. We investigated hnRNPK expression by immunohistochemistry in 188 patients with bladder cancer, and found that hnRNPK expression levels were significantly increased in bladder cancer tissues and that high-hnRNPK expression was closely correlated with poor prognosis...
November 10, 2016: Journal of Cellular and Molecular Medicine
Li Zhang, Jiling Feng, Siyuan Kong, Man Wu, Zhichao Xi, Baojun Zhang, Wenwei Fu, Yuanzhi Lao, Hongsheng Tan, Hongxi Xu
Cervical cancer is among the most frequently diagnosed cancers in females worldwide. Nujiangexathone A (NJXA), a novel compound from Garcinia nujiangensis, has been shown to have anti-cancer potential. In this study, the anti-tumor effects and the underlying mechanisms of NJXA action were investigated. Our results suggested that NJXA induced G0/G1 cell cycle arrest in HeLa and SiHa cells by down-regulating cyclins B1, E1, and A and cyclin-dependent kinases 2, 4 and 6, while selectively restoring p27. Using two-dimensional gel electrophoresis, we showed that NJXA reduced the expression of heterogeneous nuclear ribonucleoprotein K (hnRNPK) by accelerating ubiquitin-proteasome-dependent hnRNPK degradation, which then induced cell cycle arrest through the c-Myc-cyclin/Cdk-Rb-E2F1 pathway...
October 1, 2016: Cancer Letters
Ruirui Yang, Ying Zeng, Haifan Xu, Zhuo Chen, Mengqin Xiang, Yun Fu, Yufang Yin, Jing Zhong, Min Zeng, Peihua Wang, Qin You, Xi Zeng
Heterogeneous nuclear ribonucleoprotein K (hnRNP K) is one of the major pre-mRNA-binding proteins, that is involved in translational modifications. In our previous studies, we found that hnRNP K is associated with human gastric cancer. The protein levels of hnRNP K were detected in cell lines and tissue microarrays. The correlation between hnRNP K expression and patient survival rate was evaluated by Kaplan-Meier survival analysis. In addition, we also detected hnRNP K expression in preoperative and postoperative serum samples from patients with gastric cancer, and serum samples from healthy volunteers...
August 2016: Oncology Reports
Ya-Hsin Hsu, Yu-Ling Hsu, Sheng-Hung Liu, Hsin-Chia Liao, Po-Xuan Lee, Chao-Hsiung Lin, Lee-Chiang Lo, Shu-Ling Fu
Andrographolide (ANDRO) is a lactone diterpenoid compound present in the medicinal plant Andrographis paniculata which is clinically applied for multiple human diseases in Asia and Europe. The pharmacological activities of andrographolide have been widely demonstrated, including anti-inflammation, anti-cancer and hepatoprotection. However, the pharmacological mechanism of andrographolide remains unclear. Therefore, further characterization on the kinetics and molecular targets of andrographolide is essential...
2016: PloS One
Xuejuan Gao, Junxia Feng, Yujiao He, Fengmei Xu, Xiaoqin Fan, Wensi Huang, Haiting Xiong, Qiuyu Liu, Wanting Liu, Xiaohui Liu, Xuesong Sun, Qing-Yu He, Qihao Zhang, Langxia Liu
c-FLIP (cellular FLICE-inhibitory protein) is the pivotal regulator of TRAIL resistance in cancer cells, It is a short-lived protein degraded through the ubiquitin/proteasome pathway. The discovery of factors and mechanisms regulating its protein stability is important for the comprehension of TRAIL resistance by tumor cells. In this study, we show that, when H1299 lung adenocarcinoma cells are treated with TRAIL, hnRNPK is translocated from nucleus to cytoplasm where it interacts and co-localizes with GSK3β...
March 14, 2016: Scientific Reports
L Lange, A T Pagnamenta, S Lise, S Clasper, H Stewart, E S Akha, G Quaghebeur, S J L Knight, D A Keays, J C Taylor, U Kini
Kabuki syndrome is a heterogeneous condition characterized by distinctive facial features, intellectual disability, growth retardation, skeletal abnormalities and a range of organ malformations. Although at least two major causative genes have been identified, these do not explain all cases. Here we describe a patient with a complex Kabuki-like syndrome that included nodular heterotopia, in whom testing for several single-gene disorders had proved negative. Exome sequencing uncovered a de novo c.931_932insTT variant in HNRNPK (heterogeneous nuclear ribonucleoprotein K)...
September 2016: Clinical Genetics
Rebecca D Murray, Michael L Merchant, Ericka Hardin, Barbara Clark, Syed J Khundmiri, Eleanor D Lederer
Parathyroid hormone (PTH) is a key regulator of the expression and function of the type IIa sodium-phosphate cotransporter (Npt2a), the protein responsible for regulated renal phosphate reabsorption. We previously showed that PTH induces rapid decay of Npt2a mRNA through posttranscriptional mechanisms. We hypothesized that PTH-induced changes in RNA-binding protein (RBP) activity mediate the degradation of Npt2a mRNA. To address this aim, we treated opossum kidney (OK) cells, a PTH-sensitive proximal tubule cell culture model, with 100 nM PTH for 30 min and 2 h, followed by mass spectrometry characterization of the PTH-stimulated phosphoproteome...
February 1, 2016: American Journal of Physiology. Cell Physiology
R Broering, M Trippler, M Werner, C I Real, D A Megger, T Bracht, V Schweinsberg, B Sitek, M Eisenacher, H E Meyer, H A Baba, F Weber, A-C Hoffmann, G Gerken, J F Schlaak
The interferon-stimulated gene 15 (ISG15) plays an important role in the pathogenesis of hepatitis C virus (HCV) infection. ISG15-regulated proteins have previously been identified that putatively affect this proviral interaction. The present observational study aimed to elucidate the relation between ISG15 and these host factors during HCV infection. Transcriptomic and proteomic analyses were performed using liver samples of HCV-infected (n = 54) and uninfected (n = 10) or HBV-infected controls (n = 23). Primary human hepatocytes (PHH) were treated with Toll-like receptor ligands, interferons and kinase inhibitors...
May 2016: Journal of Viral Hepatitis
E Grassilli, F Pisano, A Cialdella, S Bonomo, C Missaglia, M G Cerrito, L Masiero, L Ianzano, F Giordano, V Cicirelli, R Narloch, F D'Amato, B Noli, G L Ferri, B E Leone, G Stanta, S Bonin, K Helin, R Giovannoni, M Lavitrano
Bruton's tyrosine kinase (BTK) is essential for B-cell proliferation/differentiation and it is generally believed that its expression and function are limited to bone marrow-derived cells. Here, we report the identification and characterization of p65BTK, a novel isoform abundantly expressed in colon carcinoma cell lines and tumour tissue samples. p65BTK protein is expressed, through heterogeneous nuclear ribonucleoprotein K (hnRNPK)-dependent and internal ribosome entry site-driven translation, from a transcript containing an alternative first exon in the 5'-untranslated region, and is post-transcriptionally regulated, via hnRNPK, by the mitogen-activated protein kinase (MAPK) pathway...
August 18, 2016: Oncogene
Xiaoqin Fan, Haiting Xiong, Jinmei Wei, Xuejuan Gao, Yuan Feng, Xiaohui Liu, Gong Zhang, Qing-Yu He, Jiake Xu, Langxia Liu
Osteoclast differentiation is a complex and finely regulated physiological process that involves a variety of signaling pathways and factors. Recent studies suggested that the Ser9 phosphorylation of Glycogen synthase kinase-3β (GSK3β) is required for the osteoclast differentiation. However, the precise underlying mechanism remains unclear. We have previously identified the heterogeneous nuclear ribonucleoprotein K (hnRNPK) as a putative GSK3β interactor. In the present study, we demonstrate that, during the RANKL-induced osteoclast differentiation, the PI3K/Akt-mediated Ser9 phosphorylation of GSK3β provokes the nuclear-cytoplasmic translocation of hnRNPK in an ERK-dependent manner, enhancing the cytoplasmic co-localization and interaction of GSK3β and hnRNPK...
December 7, 2015: Scientific Reports
Mallampati Saradhi, Sangeeta Kumari, Manjul Rana, Gauranga Mukhopadhyay, Rakesh K Tyagi
Pregnane and Xenobiotic Receptor (PXR), a member of nuclear receptor superfamily, acts as a 'xenosensor' in our body and modulates a network of genes involved in xenobiotic metabolism and elimination. Expression levels of PXR in certain metabolic disorders including cancer are reported to be altered and its induced expression is associated with the development of resistance towards chemotherapy and adverse drug-drug interactions. Though the transcriptional regulation of PXR target genes have been elucidated in significant details, the structure and functional control of PXR promoter itself remains inadequately explored...
December 10, 2015: Experimental Cell Research
Bita Zamiri, Mila Mirceta, Karol Bomsztyk, Robert B Macgregor, Christopher E Pearson
Unusual DNA/RNA structures of the C9orf72 repeat may participate in repeat expansions or pathogenesis of amyotrophic lateral sclerosis and frontotemporal dementia. Expanded repeats are CpG methylated with unknown consequences. Typically, quadruplex structures form by G-rich but not complementary C-rich strands. Using CD, UV and electrophoresis, we characterized the structures formed by (GGGGCC)8 and (GGCCCC)8 strands with and without 5-methylcytosine (5mCpG) or 5-hydroxymethylcytosine (5hmCpG) methylation. All strands formed heterogenous mixtures of structures, with features of quadruplexes (at pH 7...
November 16, 2015: Nucleic Acids Research
Miguel Gallardo, Hun Ju Lee, Xiaorui Zhang, Carlos Bueso-Ramos, Laura R Pageon, Mark McArthur, Asha Multani, Aziz Nazha, Taghi Manshouri, Jan Parker-Thornburg, Inmaculada Rapado, Alfonso Quintas-Cardama, Steven M Kornblau, Joaquin Martinez-Lopez, Sean M Post
hnRNP K regulates cellular programs, and changes in its expression and mutational status have been implicated in neoplastic malignancies. To directly examine its role in tumorigenesis, we generated a mouse model harboring an Hnrnpk knockout allele (Hnrnpk(+/-)). Hnrnpk haploinsufficiency resulted in reduced survival, increased tumor formation, genomic instability, and the development of transplantable hematopoietic neoplasms with myeloproliferation. Reduced hnRNP K expression attenuated p21 activation, downregulated C/EBP levels, and activated STAT3 signaling...
October 12, 2015: Cancer Cell
Erica J Hutchins, Jamie L Belrose, Ben G Szaro
Post-transcriptional control of cytoskeletal genes fine-tunes the supply of structural materials to growing axons in response to extracellular cues. In Xenopus, heterogeneous nuclear ribonucleoprotein K (hnRNPK) plays a crucial role in the nuclear export and translation of multiple cytoskeletal-related mRNAs required for axon outgrowth, and as a substrate of multiple kinases, is thus a likely molecular target of cell signaling pathways regulating such outgrowth. To study the role of hnRNPK's phosphorylation by extracellular signal-regulated kinase (ERK) in Xenopus axon outgrowth, we identified the only ERK1 phosphorylation site on Xenopus hnRNPK (S257; homologous with S284 of human hnRNPK) using an in vitro phosphorylation assay and tested its function in vivo by expressing phosphomimetic (S257D) and phosphodeficient (S257A) forms of hnRNPK in Xenopus embryos...
October 21, 2015: Neuroscience Letters
Manish Kumar, Ajay Matta, Olena Masui, Gunjan Srivastava, Jatinder Kaur, Alok Thakar, Nootan Kumar Shukla, Ajoy RoyChoudhury, Meherchand Sharma, Paul G Walfish, K W Michael Siu, Shyam Singh Chauhan, Ranju Ralhan
BACKGROUND: Post-transcriptional regulation by heterogeneous ribonucleoproteins (hnRNPs) is an important regulatory paradigm in cancer development. Our proteomic analysis revealed hnRNPD overexpression in oral dysplasia as compared with normal mucosa; its role in oral carcinogenesis remains unknown. Here in we determined the hnRNPD associated protein networks and its clinical significance in oral squamous cell carcinoma (OSCC). METHODS: Immunoprecipitation (IP) followed by tandem mass spectrometry was used to identify the binding partners of hnRNPD in oral cancer cell lines...
2015: Journal of Translational Medicine
Amotz Ziv-Av, Nissim David Giladi, Hae Kyung Lee, Simona Cazacu, Susan Finniss, Cunli Xiang, Maor H Pauker, Mira Barda-Saad, Laila Poisson, Chaya Brodie
Glioblastoma (GBM) are characterized by increased invasion into the surrounding normal brain tissue. RTVP-1 is highly expressed in GBM and regulates the migration and invasion of glioma cells. To further study RTVP-1 effects we performed a pull-down assay using His-tagged RTVP-1 followed by mass spectrometry and found that RTVP-1 was associated with the actin polymerization regulator, N-WASP. This association was further validated by co-immunoprecipitation and FRET analysis. We found that RTVP-1 increased cell spreading, migration and invasion and these effects were at least partly mediated by N-WASP...
August 14, 2015: Oncotarget
P Y Billie Au, Jing You, Oana Caluseriu, Jeremy Schwartzentruber, Jacek Majewski, Francois P Bernier, Marcia Ferguson, David Valle, Jillian S Parboosingh, Nara Sobreira, A Micheil Innes, Antonie D Kline
We report a new syndrome due to loss-of-function variants in the heterogeneous nuclear ribonucleoprotein K gene (HNRNPK). We describe two probands: one with a de novo frameshift (NM_002140.3: c.953+1dup), and the other with a de novo splice donor site variant (NM_002140.3: c.257G>A). Both probands have intellectual disability, a shared unique craniofacial phenotype, and connective tissue and skeletal abnormalities. The identification of this syndrome was made possible by a new online tool, GeneMatcher, which facilitates connections between clinicians and researchers based on shared interest in candidate genes...
October 2015: Human Mutation
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