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https://www.readbyqxmd.com/read/29328425/bioinformatics-analysis-of-the-cdk2-functions-in-neuroblastoma
#1
Lijuan Bo, Bo Wei, Zhanfeng Wang, Daliang Kong, Zheng Gao, Zhuang Miao
The present study aimed to elucidate the potential mechanism of cyclin-dependent kinase 2 (CDK2) in neuroblastoma progression and to identify the candidate genes associated with neuroblastoma with CDK2 silencing. The microarray data of GSE16480 were obtained from the gene expression omnibus database. This dataset contained 15 samples: Neuroblastoma cell line IMR32 transfected with CDK2 shRNA at 0, 8, 24, 48 and 72 h (n=3 per group; total=15). Significant clusters associated with differentially expressed genes (DEGs) were identified using fuzzy C‑Means algorithm in the Mfuzz package...
December 29, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29326019/isolation-of-a-peptide-containing-d-amino-acid-residues-that-inhibits-the-%C3%AE-helix-mediated-p53-mdm2-interaction-from-a-one-bead-one-compound-library
#2
Jumpei Morimoto, Yuki Hosono, Shinsuke Sando
α-Helix-mediated protein-protein interactions (PPIs) are important targets in biological research and drug development. Peptides containing d-amino acid residues are attractive molecules for inhibiting α-helix-mediated PPIs because of their wide surface area and high protease resistance. In this study, a peptide library was constructed using a one-bead one-compound format designed to isolate left-handed α-helical peptides, which are promising molecules as inhibitors of α-helix-mediated PPIs. Screening of the library against an α-helix-mediated PPI between MDM2 and p53 yielded an inhibitor of the PPI...
January 2, 2018: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29324237/dna-induction-of-mdm2-promotes-proliferation-of-human-renal-mesangial-cells-and-alters-peripheral-b-cells-subsets-in-pediatric-systemic-lupus-erythematosus
#3
Chen-Xing Zhang, Ji Chen, Li Cai, Jing Wu, Jia-Yuan Wang, Lan-Fang Cao, Wei Zhou, Tong-Xin Chen
The study is aimed to investigate the role of MDM2 in the pathogenesis of lupus nephritis (LN) in pediatric SLE (pSLE). We confirmed that MDM2 expression was increased in peripheral blood mononuclear cells (PBMCs) as well as renal specimen of SLE compared with that of controls by western blot and immunofluorescence staining. Percentage of apoptotic and necrotic CD4+T, CD8+T and B cells were detected by flow cytometry respectively and levels of plasma cell free DNA (cfDNA) were quantified in SLE and healthy controls (HC)...
January 8, 2018: Molecular Immunology
https://www.readbyqxmd.com/read/29323708/microrna501-5p-induces-p53-proteasome-degradation-through-the-activation-of-the-mtor-mdm2-pathway-in-adpkd-cells
#4
Lucia de Stephanis, Alessandra Mangolini, Miriam Servello, Peter C Harris, Lucio Dell'Atti, Paolo Pinton, Gianluca Aguiari
Cell proliferation and apoptosis are typical hallmarks of autosomal dominant polycystic kidney disease (ADPKD) and cause the development of kidney cysts that lead to end-stage renal disease (ESRD). Many factors, impaired by polycystin complex loss of function, may promote these biological processes, including cAMP, mTOR and EGFR signalling pathways. In addition, microRNAs (miRs) may also regulate the ADPKD related signalling network and their dysregulation contributes to disease progression. However, the role of miRs in ADPKD pathogenesis has not been fully understood, but also the function of p53 is quite obscure, especially its regulatory contribution on cell proliferation and apoptosis...
January 11, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29323264/orai3-calcium-channel-and-resistance-to-chemotherapy-in-breast-cancer-cells-the-p53-connection
#5
Jessy Hasna, Frédéric Hague, Lise Rodat-Despoix, Dirk Geerts, Catherine Leroy, David Tulasne, Halima Ouadid-Ahidouch, Philippe Kischel
Orai proteins are highly selective calcium channels playing an important role in calcium entry. Orai3 channels are overexpressed in breast cancer (BC) tissues, and involved in their proliferation, cell cycle progression and survival. Herein, we sought to address the involvement of Orai3 in resistance to chemotherapeutic drugs. Using high-throughput approaches, we investigated major changes induced by Orai3 overexpression, including downstream signaling mechanisms involved in BC chemotherapy resistance. Resistance was dependent on external calcium presence and thus Orai3 functionality...
January 11, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29319823/differentially-expressed-mrna-targets-of-differentially-expressed-mirnas-predict-changes-in-the-tp53-axis-and-carcinogenesis-related-pathways-in-human-keratinocytes-chronically-exposed-to-arsenic
#6
Laila Al-Eryani, Sabine Waigel, Ashish Tyagi, Jana Peremarti, Samantha F Jenkins, Chendil Damodaran, J Christopher States
Background: Arsenic is a widely distributed toxic natural element. Chronic arsenic ingestion causes several cancers, especially skin cancer. Arsenic-induced cancer mechanisms are not well defined, but several studies indicate that mutation is not the driving force and that microRNA expression changes play a role. Chronic low arsenite exposure malignantly transforms immortalized human keratinocytes (HaCaT), serving as a model for arsenic-induced skin carcinogenesis. Hypothesis: Early changes in miRNA expression in HaCaT cells chronically exposed to arsenite will reveal early steps in transformation...
January 8, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29309301/mdm2-amplification-in-intrahepatic-cholangiocarcinomas-its-relationship-with-large-duct-type-morphology-and-uncommon-kras-mutations
#7
Sung Joo Kim, Masayuki Akita, You-Na Sung, Kohei Fujikura, Jae Hoon Lee, Shin Hwang, Eunsil Yu, Kyoko Otani, Seung-Mo Hong, Yoh Zen
The present study aimed to characterize intrahepatic cholangiocarcinomas (iCCAs) with MDM2 amplification. A total of 213 cases of iCCA were examined using dual-color in situ hybridization for MDM2, immunohistochemistry for p53 and SMAD4, and gene sequencing for KRAS and IDH1/2. In situ hybridization on tissue microarrays identified MDM2 amplification in 13/213 (6%) cases. Using the recently proposed classification scheme of iCCAs (small-duct and large-duct types), all MDM2-amplified cases were of the large-duct type (13/110 cases, 12%)...
January 5, 2018: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/29309298/clarifying-the-distinction-between-malignant-peripheral-nerve-sheath-tumor-and-dedifferentiated-liposarcoma-a-critical-reappraisal-of-the-diagnostic-utility-of-mdm2-and-h3k27me3-status
#8
Naohiro Makise, Masaya Sekimizu, Takashi Kubo, Susumu Wakai, Nobuyoshi Hiraoka, Motokiyo Komiyama, Masashi Fukayama, Akira Kawai, Hitoshi Ichikawa, Akihiko Yoshida
Malignant peripheral nerve sheath tumor (MPNST) and dedifferentiated liposarcoma (DDLPS) are 2 major types of pleomorphic spindle cell sarcoma. The differentiation of MPNST and DDLPS by histomorphology alone can be problematic. Although MDM2 amplification and PRC2 alteration leading to H3K27me3 deficiency are genetic hallmarks of DDLPS and MPNST, respectively, a small number of MDM2-amplified MPNSTs and H3K27me3-deficient DDLPSs have been reported in the literature. We systematically compared MDM2 and H3K27me3 status in 68 MPNSTs and 47 DDLPSs...
January 5, 2018: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/29307627/dedifferentiated-liposarcoma-composed-predominantly-of-rhabdoid-epithelioid-cells-a-frequently-misdiagnosed-highly-aggressive-variant
#9
Abbas Agaimy, Michael Michal, Ladislav Hadravsky, Michal Michal
Dedifferentiated liposarcoma is one of the most common sarcoma types in adults with a predilection for the retroperitoneum. We have recently encountered 6 cases of DDL composed predominantly of rounded, rhabdoid or epithelioid cells mimicking rhabdoid melanoma, epithelioid rhabdomyosarcoma or undifferentiated carcinoma. Patients were 5 males and one female aged 64 to 81 years (median, 68). Tumors originated in the retroperitoneum (n=5; 3 in the psoas muscle) and deep soft tissue of the thigh (n=1). All 3 patients with follow-up died of metastatic disease within 4 to 8 months...
January 4, 2018: Human Pathology
https://www.readbyqxmd.com/read/29302672/synthesis-of-spiro-tetrahydrothiopyran-oxindoles-by-michael-aldol-cascade-reactions-discovery-of-potential-p53-mdm2-inhibitors-with-good-antitumor-activity
#10
Shengzheng Wang, Shuqiang Chen, Zhongjie Guo, Shipeng He, Fan Zhang, Xueying Liu, Weiping Chen, Shengyong Zhang, Chunquan Sheng
Using proline as the catalyst, an organocatalytic Michael-aldol cascade reaction was developed for the synthesis of spiro-tetrahydrothiopyran oxindoles. The highly functionalized scaffold was assembled in moderate to good yields (51-78%) and excellent diastereoselectivities (>20 : 1 dr). Interestingly, the oxindoles displayed moderate to good in vitro antitumor activities and were validated as p53-MDM2 inhibitors, which represented promising lead compounds for antitumor drug discovery.
January 5, 2018: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/29301793/o-glcnacylation-of-the-tumor-suppressor-foxo3-triggers-aberrant-cancer-cell-growth
#11
Heon Shin, Hyun-Jeong Cha, Keun Na, Min Jung Lee, Jin-Young Cho, Chae-Yeon Kim, Eun Kyung Kim, Chang Moo Kang, Hoguen Kim, Young-Ki Paik
Post-translational modifications of tumor suppressors can induce abnormal cell growth. Here we identify site-specific O-GlcNAcylation as a critical block of FOXO3 that may abrogate a part of the p53 pathway, resulting in aberrant cancer cell growth. Of seven O-GlcNAcylation sites identified within the FOXO3 transactivation domain, we found that changes in O-GlcNAcylation at Ser284 modulated p21-mediated cancer cell growth. Overexpression of either O-GlcNAcylated FOXO3 (FOX-OV) or a Ser-to-Ala mutant (S284A) in PANC-1 cells indicated that S284 O-GlcNAc acts as a critical block of the FOXO tumor suppressor and induces proliferation in PANC-1 cancer cells by stimulating the MDM2-p53-p21 axis...
January 4, 2018: Cancer Research
https://www.readbyqxmd.com/read/29297949/effect-of-17-allylamino-17-demethoxygeldanamycin-17-aag-on-akt-protein-expression-is-more-effective-in-head-and-neck-cancer-cell-lineages-that-retain-pten-protein-expression
#12
Flávia Sirotheau Corrêa Pontes, Hélder Antônio Rebelo Pontes, Lucas Lacerda de Souza, Adriana Souza de Jesus, Andrea Maia Correa Joaquim, Ligia Akiko Ninokata Miyahara, Felipe Paiva Fonseca, Décio Dos Santos Pinto Júnior
OBJECTIVES: The aim of this study was to evaluate the expression of Akt, PTEN, Mdm2 and p53 proteins in three different head and neck squamous cell carcinoma (HNSCC) cell lines (HN6, HN19 and HN30), all of them treated with epidermal growth factor (EGF) and 17-allylamino-17-demethoxygeldanamycin (17-AAG), an inhibitor of Hsp90 protein. MATERIAL AND METHODS: Immunofluorescence and western blot were performed in order to analyze the location and quantification, respectively, of proteins under the action 17-AAG and EGF...
January 3, 2018: Journal of Oral Pathology & Medicine
https://www.readbyqxmd.com/read/29295817/regulation-of-the-mdm2-p53-pathway-by-the-ubiquitin-e3-ligase-march7
#13
Kailiang Zhao, Yang Yang, Guang Zhang, Chenfeng Wang, Decai Wang, Mian Wu, Yide Mei
The tumor suppressor p53 plays a prominent role in the protection against cancer. The activity of p53 is mainly controlled by the ubiquitin E3 ligase Mdm2, which targets p53 for proteasomal degradation. However, the regulation of Mdm2 remains not well understood. Here, we show that MARCH7, a RING domain-containing ubiquitin E3 ligase, physically interacts with Mdm2 and is essential for maintaining the stability of Mdm2. MARCH7 catalyzes Lys63-linked polyubiquitination of Mdm2, which impedes Mdm2 autoubiquitination and degradation, thereby leading to the stabilization of Mdm2...
January 2, 2018: EMBO Reports
https://www.readbyqxmd.com/read/29290977/btk-blocks-the-inhibitory-effects-of-mdm2-on-p53-activity
#14
Miran Rada, Mohammad Althubiti, Akang E Ekpenyong-Akiba, Koon-Guan Lee, Kong Peng Lam, Olga Fedorova, Nickolai A Barlev, Salvador Macip
p53 is a tumour suppressor that is activated in response to various types of stress. It is regulated by a complex pattern of over 50 different post-translational modifications, including ubiquitination by the E3 ligase MDM2, which leads to its proteasomal degradation. We have previously reported that expression of Bruton's Tyrosine Kinase (BTK) induces phosphorylation of p53 at the N-terminus, including Serine 15, and increases its protein levels and activity. The mechanisms involved in this process are not completely understood...
December 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/29287200/gramine-attenuates-egfr-mediated-inflammation-and-cell-proliferation-in-oral-carcinogenesis-via-regulation-of-nf-%C3%AE%C2%BAb-and-stat3-signaling
#15
Arunkumar Ramu, Suresh Kathiresan, Hemavardhini Ramadoss, Anandhi Nallu, Ramachandran Kaliyan, Theerthu Azamuthu
Gramine, a natural indole alkaloid found in Hordeum vulgare has been possesses anti-mutagenic properties. The aim of the present study was to evaluate the effect of gramine on inflammation and proliferation in 7,12-dimethylbenz[a]anthracene(DMBA)-induced hamster buccal pouch (HBP) carcinogenesis. Epidermal growth factor receptor (EGFR) tyrosine kinase phosphorylation trigged PI3K/Akt/mTOR and JAK signaling that activates NF-κB and STAT3. In contrast, gramine suppressed EGFR tyrosine kinase phosphorylation and simultaneously inhibiting PI3K/Akt/mTOR and JAK phosphorylation, thereby blockage NF-κB and STAT3 nuclear translocation...
December 26, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29283338/aqueous-extract-of-smokeless-tobacco-gutkha-deregulates-tumor-suppressor-and-dna-repair-response-in-a-murine-model-of-smokeless-tobacco-use
#16
Angom Ranjana Devi, Mahuya Sengupta, Yashmin Choudhury
The effect of smokeless tobacco (gutkha) was investigated by treating male and female Swiss Albino mice with an aqueous extract of smokeless tobacco (AEST). AEST was administered at a dose of 25 mg kg-1 body weight per day for different time periods (6, 12, 16, and 24 weeks), and control animals were provided only drinking water without AEST for the same period. Control and AEST-treated mice were observed for different oxidative stress parameters, nitric oxide (NO) release, and myeloperoxidase (MPO) release, and they were evaluated for alterations in tumor suppressor and DNA repair responses in the liver and spleen...
2017: Journal of Environmental Pathology, Toxicology and Oncology
https://www.readbyqxmd.com/read/29282301/inhibition-of-mdm2-by-a-rhein-derived-compound-aq-101-suppresses-cancer-development-in-scid-mice
#17
Lubing Gu, Hailong Zhang, Tao Liu, Alexander Draganov, Sha Yi, Binghe Wang, Muxiang Zhou
A novel small-molecule anthraquinone (AQ) analog, AQ-101, which was synthesized through chemical modification of the core structures of rhein, exhibited potent anticancer activity. In the present study, we evaluated the cancer-inhibiting mechanism of AQ-101 and tested the therapeutic potential of this compound for treating cancer in mice. We found that AQ-101 was able to induce MDM2 protein degradation through a self-ubiquitination and proteasome-mediated mechanism. This AQ-101-induced MDM2 downregulation led to activation of p53, which contributed to apoptosis of acute lymphoblastic leukemia (ALL), especially those with a wild-type p53 phenotype and MDM2 expression in vitro and in vivo...
December 27, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29273639/adverse-effects-on-%C3%AE-adrenergic-receptor-coupling-ischemic-postconditioning-failed-to-preserve-long-term-cardiac-function
#18
Rolf Schreckenberg, Péter Bencsik, Martin Weber, Yaser Abdallah, Csaba Csonka, Kamilla Gömöri, Krisztina Kiss, János Pálóczi, Judit Pipis, Márta Sárközy, Péter Ferdinandy, Rainer Schulz, Klaus-Dieter Schlüter
BACKGROUND: Ischemic preconditioning (IPC) and ischemic postconditioning (IPoC) are currently among the most efficient strategies protecting the heart against ischemia/reperfusion injury. However, the effect of IPC and IPoC on functional recovery following ischemia/reperfusion is less clear, particularly with regard to the specific receptor-mediated signaling of the postischemic heart. The current article examines the effect of IPC or IPoC on the regulation and coupling of β-adrenergic receptors and their effects on postischemic left ventricular function...
December 22, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/29260852/targeting-the-prion-like-aggregation-of-mutant-p53-to-combat-cancer
#19
Jerson L Silva, Elio A Cino, Iaci N Soares, Vitor F Ferreira, Guilherme A P de Oliveira
Prion-like behavior of several amyloidogenic proteins has been demonstrated in recent years. Despite having functional roles in some cases, irregular aggregation can have devastating consequences. The most commonly known amyloid diseases are Alzheimer's, Parkinson's, and Transmissible Spongiform Encephalopathies (TSEs). The pathophysiology of prion-like diseases involves the structural transformation of wild-type (wt) proteins to transmissible forms that can convert healthy proteins, generating aggregates. The mutant form of tumor suppressor protein, p53, has recently been shown to exhibit prion-like properties...
December 20, 2017: Accounts of Chemical Research
https://www.readbyqxmd.com/read/29259342/non-structural-protein-1-of-h3n2-influenza-a-virus-induces-nucleolar-stress-via-interaction-with-nucleolin
#20
Yinxia Yan, Yongming Du, Gefei Wang, Kangsheng Li
The nucleolus is a stress sensor associated with cell cycle progression and a central hub for the replication of pathogenic RNA viruses. However, the role of nucleolus in influenza A virus infection has not been well studied. Here we show that the interaction between NS1 protein of influenza A/Shantou/602/06 (H3N2) and nucleolin, a ubiquitous protein of nucleolus repressed RNA Pol I-dependent transcription via establishing hyper-methylation in the UCE of rRNA gene promoter. NS1 expressed cells showed significant association of ribosomal proteins with MDM2, and p53 accumulation, suggesting induced nucleolar stress...
December 19, 2017: Scientific Reports
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