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p53 cancer

Ziling Fang, Bo Cao, Jun-Ming Liao, Jun Deng, Kevin D Plummer, Peng Liao, Tao Liu, Wensheng Zhang, Kun Zhang, Li Li, David Margolin, Shelya X Zeng, Jianping Xiong, Hua Lu
Ribosomal proteins (RPs) play important roles in modulating the MDM2-p53 pathway. However, less is known about the upstream regulators of the RPs. Here we identify SPIN1 (Spindlin 1) as a novel binding partner of human RPL5/uL18 that is important for this pathway. SPIN1 ablation activates p53, suppresses cell growth, reduces clonogenic ability, and induces apoptosis of human cancer cells. Mechanistically, SPIN1 sequesters uL18 in the nucleolus, preventing it from interacting with MDM2, and thereby alleviating uL18-mediated inhibition of MDM2 ubiquitin ligase activity towards p53...
March 16, 2018: ELife
Huizhen Fan, Chunyan Jiang, Baoyuan Zhong, Jianwen Sheng, Ting Chen, Qingqing Chen, Jingtao Li, Hongchuan Zhao
Matrine may be protective against colorectal cancer (CRC), but how it may work is unclear. Thus, we explored the underlying mechanisms of matrine in CRC. Matrine-related proteins and CRC-related genes and therapeutic targets of matrine in CRC were predicted using a network pharmacology approach. Five targets, including interleukin 6 (IL-6), the 26S proteasome, tumor necrosis factor alpha (TNF- α ), transforming growth factor beta 1 (TGF- β 1) and p53, and corresponding high-mobility group box 1 (HMGB1) signaling and T helper cell differentiation were thought to be associated with matrine's mechanism...
2018: Journal of Immunology Research
Zhong Ni, Xiting Wang, Tianchen Zhang, Linlin Li, Jianxue Li
Small cell lung cancer (SCLC) is the subtype of lung cancer with the highest degree of malignancy and the lowest degree of differentiation. The purpose of this study was to investigate the molecular mechanisms of SCLC using bioinformatics analysis, and to provide new ideas for the early diagnosis and targeted therapy of SCLC. Microarray data were downloaded from Gene Expression Omnibus. Differentially expressed genes (DEGs) in SCLC were compared with the normal lung samples and identified. Gene Ontology (GO) function and pathway analysis of DEGs was performed through the DAVID database...
April 2018: Experimental and Therapeutic Medicine
Naira F Z Schneider, Claudia Cerella, Jin-Young Lee, Aloran Mazumder, Kyung Rok Kim, Annelise de Carvalho, Jennifer Munkert, Rodrigo M Pádua, Wolfgang Kreis, Kyu-Won Kim, Christo Christov, Mario Dicato, Hyun-Jung Kim, Byung Woo Han, Fernão C Braga, Cláudia M O Simões, Marc Diederich
Cardiac glycosides (CGs) are natural compounds used traditionally to treat congestive heart diseases. Recent investigations repositioned CGs as potential anticancer agents. To discover novel cytotoxic CG scaffolds, we selected the cardenolide glucoevatromonoside (GEV) out of 46 CGs for its low nanomolar anti-lung cancer activity. GEV presented reduced toxicity toward non-cancerous cell types (lung MRC-5 and PBMC) and high-affinity binding to the Na+ /K+ -ATPase α subunit, assessed by computational docking...
2018: Frontiers in Pharmacology
Sheng Zhang, Chengrong Xie, Honghe Li, Kang Zhang, Jie Li, Xiaomin Wang, Zhenyu Yin
Ubiquitin-specific protease 11 (USP11) is a deubiquitinating enzyme that exerts its biological functions by regulating multiple signaling pathways such as p53, NF-κB, TGF-β, and Hippo. A large body of evidence supports a link between UPS11 and tumorigenesis. However, the clinical significance and biological function of USP11 in hepatocellular carcinoma (HCC) remains unclear. Here, USP11 expression was assessed by immunohistochemistry in a pilot series of 71 HCC clinical samples, and the association between USP11 expression and clinicopathological features and overall survival time was analyzed...
March 15, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
Kati Richter, Teija Paakkola, Daniela Mennerich, Kateryna Kubaichuk, Anja Konzack, Heidi Ali-Kippari, Nina Kozlova, Peppi Koivunen, Kirsi-Maria Haapasaari, Arja Jukkola-Vuorinen, Hanna-Riikka Teppo, Elitsa Y Dimova, Risto Bloigu, Zoltan Szabo, Risto Kerkelä, Thomas Kietzmann
Recent studies suggest that the ubiquitin-specific protease USP28 plays an important role in cellular repair and tissue remodeling, which implies that it has a direct role in carcinogenesis. The carcinogenic potential of USP28 was investigated in a comprehensive manner using patients, animal models, and cell culture. The findings demonstrate that overexpression of USP28 correlates with a better survival in patients with invasive ductal breast carcinoma. Mouse xenograft experiments with USP28-deficient breast cancer cells also support this view...
March 15, 2018: Molecular Cancer Research: MCR
Soyoung Park, Ah-Young Oh, Jung-Hyun Cho, Min-Ho Yoon, Tae-Guen Woo, Somi Kang, Ho-Young Lee, Yunjin Jung, Bum-Joon Park
Quinacrine (QNC), anti-protozoan drug commonly used against Malaria and Giardiasis, has been recently tried for rheumatics and prion diseases via drug repositioning. In addition, several reports suggest anti-tumor effects of QNC through suppression of NF-κB and activation of p53. This study, demonstrates the anti-cancer effect of QNC via a novel pathway through the elimination of check point kinase 1/2 (Chk1/2) under p53 inactivated conditions. Inhibition of p53, by PFT-α or siRNA, promotes QNC-induced apoptosis in normal fibroblast and p53-intact cancer cells...
March 15, 2018: Molecular Cancer Research: MCR
Natalia Papadopoulos, Johan Lennartsson, Carl-Henrik Heldin
Translocation of full-length or fragments of receptors to the nucleus has been reported for several tyrosine kinase receptors. In this paper, we show that a fraction of full-length cell surface platelet-derived growth factor (PDGF) receptor β (PDGFRβ) accumulates in the nucleus at the chromatin and the nuclear matrix after ligand stimulation. Nuclear translocation of PDGFRβ was dependent on PDGF-BB-induced receptor dimerization, clathrin-mediated endocytosis, β-importin, and intact Golgi, occurring in both normal and cancer cells...
March 15, 2018: Journal of Cell Biology
Minle Li, Keyu Gao, Laili Chu, Junnian Zheng, Jing Yang
Aurora kinase A (Aurora-A), a member of the Aurora family of serine/threonine kinases, plays a critical role in multiple steps of mitotic progression, including microtubule stability during the G1 phase of the cell cycle, chromosome alignment and segregation, and cytokinesis and is aberrantly expressed in various types of human cancers. In addition to its classic functions, recent studies have indicated that Aurora-A is critical for controlling self-renewal of embryonic stem cells through negative regulation of p53...
March 12, 2018: International Journal of Biochemistry & Cell Biology
Jing Chen, Yan Qi, Cui-Fang Liu, Jing-Min Lu, Yan Shi
INTRODUCTION: MicroRNAs have been increasing prevalent due to the association of their deregulation with neurodegenerative disorders, especially Alzheimer's disease (AD). However, the association between miRNAs and AD hasn't been made clear. PURPOSE: In this study, Nine representative miRNA datasets were selected for the identification of the critical miRNAs by analyzing the overlap relations among them. TargetScan software was further used to predict the target genes of these miRNAs...
March 15, 2018: Journal of Gene Medicine
Weinan Guo, Jinyuan Ma, Tianli Pei, Tao Zhao, Sen Guo, Xiuli Yi, Yu Liu, Shiyu Wang, Guannan Zhu, Zhe Jian, Tianwen Gao, Chunying Li, Wenjun Liao, Qiong Shi
Melanoma is the most malignant skin cancer with increasing incidence worldwide. Although innovative therapies such as BRAF inhibitor and immune checkpoint inhibitor have gained remarkable advances, metastatic melanoma remains an incurable disease for its notorious aggressiveness. Therefore, further clarification of the underlying mechanism of melanoma pathogenesis is critical for the improvement of melanoma therapy. Ubiquitination is an important regulatory event for cancer hallmarks and melanoma development, and the deubiquitinating enzymes including ubiquitin-specific peptidase (USP) families are greatly implicated in modulating cancer biology...
March 14, 2018: Journal of Cellular and Molecular Medicine
Hyun-Jung Moon, Hak-Bong Kim, Su-Hoon Lee, So-Eun Jeun, Chi-Dug Kang, Sun-Hee Kim
NSAIDs (non-steroidal anti-inflammatory drugs) have potential use as anticancer agents, either alone or in combination with other cancer therapies. We found that NSAIDs including celecoxib (CCB) and ibuprofen (IBU) significantly potentiated the cytotoxicity of Hsp90 inhibitors in human multidrug-resistant (MDR) cells expressing high levels of mutant p53 (mutp53) protein and P-glycoprotein (P-gp), and reversed Hsp90 inhibitor resistance caused by activation of heat shock factor 1 (HSF1) and by up-regulation of heat shock proteins (Hsps) and P-gp...
February 16, 2018: Oncotarget
Takuya Yamane, Izumi Kato-Ose, Tatsuji Sakamoto, Yoshihisa Nakano
Background: Asparaginyl endopeptidase, also known as legumain (EC shows strong activity in the mouse kidney. Legumain is also highly expressed in tumors. DJ-1/PARK7 is a Parkinson's disease- and cancer-associated protein. DJ-1 is a coactivator of various transcription factors. Recently, we reported that transcription of the legumain gene is regulated by p53 through DJ-1. Methods: We measured the secretion levels of legumain in a conditioned medium of DJ-1 knockout cells and in serum from DJ-1 knockout mice using Western blotting and ELISA...
2018: Open Biochemistry Journal
Sujuan Yuan, Tiankui Qiao, Xuan Li, Xibing Zhuang, Wei Chen, Xue Chen, Qi Zhang
Unmethylated cytosine-phosphorothioate-guanine (CpG)-containing oligodeoxynucleotides (ODNs) are synthetic DNA sequences that mimic bacterial DNA, and are known to serve as ligands for Toll-like receptor 9 (TLR9). The interaction between a CpG ODNs with TLR9 activates the complex downstream cascade that contributes to exerting its function. In the present study, the results of clonogenic assays demonstrated that the activation of TLR9 by CpG ODNs significantly increased the radiosensitivity of A549 lung cancer cells, with a sensitivity enhancement ratio (SER) of 1...
April 2018: Oncology Letters
Yufeng Du, Xiaoyan Hao, Xuejun Liu
The present study aimed to investigate the expression of long non-coding RNA (lncRNA) cyclin dependent kinase inhibitor-2B-antisense RNA 1 CDKN2B-AS1 in patients with peripheral blood of idiopathic pulmonary fibrosis (IPF). A total of 24 patients with IPF and 24 healthy controls were included in the study, four patients with IPF and four healthy controls were selected randomly to extract RNA. There were no other diseases such as hypertension and diabetes in the two groups. RNA from peripheral blood was extracted by high-throughput sequencing and bioinformatics analysis was performed...
April 2018: Oncology Letters
Xiao Sun, Tanxiao Huang, Fangsheng Cheng, Kaibing Huang, Ming Liu, Wan He, Mingwei Li, Xiaoni Zhang, Mingyan Xu, Shifu Chen, Ligang Xia
Postoperative monitoring for patients with colorectal cancer (CRC) requires sensitive biomarkers that are associated with medical response and adjuvant therapy following surgery. Conventional tumor biomarkers [including carcinoembryonic antigen (CEA), CA19-9 and CA125] are widely used, but none of the markers provide high sensitivity or specificity. Previous studies indicated that circulating tumor DNA (ctDNA) is useful for postoperative monitoring of patients with cancer. However, the majority of previous studies involved patients with lung cancer, and therefore further studies are required which investigate patients with CRC...
April 2018: Oncology Letters
Luchao Chen, Zhongxia Lu, Yongle Yang, Lijun Du, Xiaofang Zhou, Yitao Chen
Gastric cancer is one of the most common cancers globally with high rates of morbidity and mortality. Purified Omphalia lapidescens protein (pPe O p) is a protein extracted from the sclerotium of Omphalia lapidescens . The present study aimed to investigate the effects of pPe O p on the viability, migration, cell cycle progression and apoptosis of SGC-7901 cells. The expression of numerous proteins, namely matrix metallopeptidase (MMP)2, MMP9, p53, caspase-3, B-cell lymphoma (Bcl)-2, cyclin A2, cyclin B1, cyclin D1, cyclin dependent kinase (CDK)1, CDK2 and CDK4, were investigated using western blot analysis and reverse transcription-quantitative polymerase chain reaction...
April 2018: Oncology Letters
Zhaoyun Liu, Hui Liu, Xin Yuan, Yihao Wang, Lijuan Li, Guojin Wang, Jia Song, Zonghong Shao, Rong Fu
Pim-2 is a serine/threonine protein kinase that is highly expressed in various types of cancer, with essential roles in the regulation of signal transduction cascades, which promote cell survival and proliferation. The present study demonstrated that Pim-2 was expressed in cells lines derived from hematopoietic tumors and lung cancer. In vitro , downregulation of Pim-2 by short interfering RNA inhibited proliferation and delayed G0 /G1 cell cycle progression in K562 leukemia, RPMI-8226 multiple myeloma, and H1299 and A549 non-small cell lung carcinoma cell lines...
April 2018: Oncology Letters
Arunee Hematulin, Sutiwan Meethang, Kitsana Utapom, Sopit Wongkham, Daniel Sagan
Radiotherapy has been accounted as the most comprehensive cancer treatment modality over the past few decades. However, failure of this treatment modality occurs in several malignancies due to the resistance of cancer cells to radiation. It was previously reported by the present authors that defective cell cycle checkpoints could be used as biomarkers for predicting the responsiveness to radiation in individual patients with cholangiocarcinoma (CCA). However, identification of functional defective cell cycle checkpoints from cells from a patient's tissues is cumbersome and not applicable in the clinic...
March 2018: Oncology Letters
Nathália Kersting, Bárbara Kunzler Souza, Igor Araujo Vieira, Rafael Pereira Dos Santos, Danielly Brufatto Olguins, Lauro José Gregianin, André Tesainer Brunetto, Algemir Lunardi Brunetto, Rafael Roesler, Caroline Brunetto de Farias, Gilberto Schwartsmann
OBJECTIVE: Ewing sarcoma (ES) is a type of childhood cancer probably arising from stem mesenchymal or neural crest cells. The epidermal growth factor receptor (EGFR) acts as a driver oncogene in many types of solid tumors. However, its involvement in ES remains poorly understood. METHODS: Human SK-ES-1 and RD-ES ES cells were treated with EGF, the EGFR inhibitor tyrphostin (AG1478), or phosphoinositide 3-kinase (PI3K) or extracellular-regulated kinase (ERK)/mitogen-activated kinase (MAPK) inhibitors...
March 14, 2018: Oncology
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