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Liwei Zhang, Yue Jin, Hao Yang, Yu Li, Chao Wang, Yongheng Shi, Yu Wang
Epithelial ovarian cancer (EOC) has a very poor prognosis because of tumor invasiveness. Here, we reported that SMYD3 a lysine methyltransferase was frequently upregulated in EOC and associated with poor prognosis. A series of in vitro assays demonstrated that SMYD3 significantly upgraded the migration ability of EOC cells. The results of in vivo EOC metastasis models further confirmed that overexpression of SMYD3 promoted EOC progression. Mechanistic investigations indicated SMYD3 cloud decrease p53 protein stability and induce epithelial-mesenchymal transition (EMT) in EOC cells...
April 19, 2019: Carcinogenesis
Qinchuan Wang, Huakang Tu, Meiling Zhu, Dong Liang, Yuanqing Ye, David W Chang, Yin Long, Xifeng Wu
Obesity is one of modifiable risk factors for clear cell renal cell cancer (ccRCC). We aim to identify the association between obesity-driven biomarkers and ccRCC risk. This is a retrospective, two-phases, case-control study involving 682 cases and 733 controls. Obesity-driven biomarkers (GIP, C-peptide, Insulin, Resistin, Adipsin, PYY, PPY, IL-6, TNF-α, PAI1, MCP1, Lipocalin2, Leptin, Adiponectin) were measured using the Milliplex method. Multivariate logistic regression was used to assess the associations between biomarkers and ccRCC risk...
April 17, 2019: Carcinogenesis
Yutian Zou, Shaoquan Zheng, Weikai Xiao, Xinhua Xie, Anli Yang, Guanfeng Gao, Zhenchong Xiong, Zhicheng Xue, Hailin Tang, Xiaoming Xie
As a new rising star of non-coding RNA, circular RNAs (circRNAs) emerged as vital regulators with biological functions in diverse of cancers. However, the function and precise mechanism of the vast majority of circRNAs in triple-negative breast cancer (TNBC) occurrence and progression have not been clearly elucidated. In the current study, we identified and further investigated hsa_circ_0002453 (circRAD18) by analyzing our previous microarray profiling. Expression of circRAD18 was found significantly up-regulated in TNBC compared with normal mammary tissues and cell lines...
April 17, 2019: Carcinogenesis
Dingyuan Luo, Magdalena Fraga-Lauhirat, Jonathan Millings, Cristella Ho, Emily M Villarreal, Teresa C Fletchinger, James V Bonfiglio, Leyda Mata, Matthew D Nemesure, Lauren E Bartels, Ruixue Wang, Basil Rigas, Gerardo G Mackenzie
New therapeutic strategies against glioblastoma multiforme (GBM) are urgently needed. Signal transducer and activator of transcription 3 (STAT3), constitutively active in many GBM tumors, plays a major role in GBM tumor growth and represents a potential therapeutic target. We have previously documented that phospho-valproic acid (MDC-1112), which inhibits STAT3 activation, possesses strong anticancer properties in multiple cancer types. In this study, we explored the anticancer efficacy of MDC-1112 in preclinical models of GBM, and evaluated its mode of action...
April 17, 2019: Carcinogenesis
Satheesh Kumar Sengodan, Sreelatha K Hemalatha, Revathy Nadhan, Thara Somanathan, Arun Peter Mathew, Arkadiusz Chil, Janusz Kopczynski, Rakesh Sathish Nair, Jerald Mahesh Kumar, Priya Srinivas
β-hCG expression in breast cancer is highly controversial with reports supporting both protective and tumorigenic effects. It has also been reported that risk of breast cancer at an early age is increased with full term pregnancies if a woman is a BRCA1 mutation carrier. We have already demonstrated that BRCA1 defective cells express high levels of β-hCG and that when BRCA1 is restored, β-hCG level is reduced. Also, BRCA1 can bind to the promoter and reduce the levels of β-hCG. β-hCG induces tumorigenecity in BRCA1 defective cells by directly binding to TGFBRII and induces TGFBRII mediated cell proliferation...
April 9, 2019: Carcinogenesis
Yehua Shen, Litao Xu, Zhouyu Ning, Luming Liu, Junhua Lin, Hao Chen, Zhiqiang Meng
β-catenin is a subunit of the cadherin protein complex and acts as an intracellular signal transducer in the Wnt signaling pathway that mediates multiple cellular processes, such as cell migration and invasion. HDAC2 (histone deacetylase 2), a deacetylase that maintains histone H3 in a deacetylated state in the promoter region of Wnt-targeted genes where β-catenin is bound, negatively regulating -catenin activation. However, the regulation of HDAC2/-catenin pathway remains unclear. Here we report ARHGAP4 as a new regulator of the -catenin pathway that regulates cell invasion and migration of pancreatic cancer as well as the downstream effector MMP2 and MMP9 expression in vitro...
April 8, 2019: Carcinogenesis
Ji-Wei Chang, Yuduan Ding, Muhammad Tahir Ul Qamar, Yin Shen, Junxiang Gao, Ling-Ling Chen
Prioritization of cancer-related genes from gene expression profiles and proteomic data is vital to improve the targeted therapies research. Although computational approaches have been complementing high-throughput biological experiments on the understanding of human diseases, it still remains a big challenge to accurately discover cancer-related proteins/genes via automatic learning from large-scale protein/gene expression data and protein-protein interaction data. Most of the existing methods are based on network construction combined with gene expression profiles, which ignore the diversity between normal samples and disease cell lines...
April 4, 2019: Carcinogenesis
Alexandra Muñoz, Will J Eldridge, Nina Munkholt Jakobsen, Helle Sørensen, Adam Wax, Max Costa
No abstract text is available yet for this article.
April 3, 2019: Carcinogenesis
Akhil Soman ThekkePurakkal, Belinda Nicolau, Robert D Burk, Eduardo L Franco, Nicolas F Schlecht
The evidence for genetic polymorphisms in genes encoding Cytochrome P450 (CYP) and Glutathione S-transferase (GST) enzymes as risk factors for squamous cell carcinomas of the head and neck (SCCHN) in Caucasians is conflicting. Furthermore, the interactive effects with smoking have not been documented. We estimated the effects of five single nucleotide polymorphisms (SNPs) and two copy number variants associated with CYP and GST genes, as well as their interactive effects with smoking, on SCCHN risk among Caucasians from a case-control study conducted in Montreal, Canada...
April 2, 2019: Carcinogenesis
Qiao Yi Chen, Thomas Des Marais, Max Costa
The special AT-rich DNA binding protein (SATB2) is a nuclear matrix-associated protein and an important transcription factor for biological development, gene regulation and chromatin remodeling. Aberrant regulation of SATB2 has been found to highly correlate with various types of cancers including lung, colon, prostate, breast, gastric and liver. Recent studies have revealed that a subset of small non-coding RNAs, termed microRNAs (miRNAs), are important regulators of SATB2 function. As post-transcriptional regulators, miRNAs have been found to have fundament importance maintaining normal cellular development...
March 27, 2019: Carcinogenesis
Haoyi Ji, Na Liu, Jing Li, Dawei Chen, Dan Luo, Qian Sun, Yingchun Yin, Yanli Liu, Bing Bu, Xiaoyang Chen, Jingxin Li
Stress is associated with an increased risk of lung metastasis in melanoma. However, the underlying mechanism is elusive. Oxytocin (OXT), a neurohormone produced by the hypothalamus, plays a vital role in laboring induction and lactation. Emerging evidence suggests that OXT also regulates human emotions, social cognition, social behaviors and stress-related disorders. Here,wereportedthat a significant up-regulation of oxytocin receptors (OXTRs) was observed in malignant melanoma. The activation of oxytocin receptors (OXTRs) dramatically promoted migration, invasion and angiogenesis but not the proliferation of melanoma cells invitro and invivo via β-arrestin 2-dependent ERK-VEGF/ MMP-2 pathway...
March 22, 2019: Carcinogenesis
Tommaso A Dragani, Francesca Colombo, Elizabeth N Pavlisko, Victor L Roggli
No abstract text is available yet for this article.
March 19, 2019: Carcinogenesis
Junko Ishiguro, Hidemi Ito, Megumi Tsukamoto, Hiroji Iwata, Hiroshi Nakagawa, Keitaro Matsuo
The adenosine triphosphate-binding cassette (ABC) transporter superfamily consists of membrane proteins which translocate various substrates across membranes. Because ABCC11, a member ABC transporter, is highly expressed in breast cancer tissue, it may be involved in the efflux of conjugated estrogen metabolites. rs17822931, a functional single nucleotide polymorphism (SNP) in ABCC11, may play a role in the carcinogenesis of breast cancer via estrogen. Here, we aimed to evaluate the association between ABCC11 rs17822931 and breast cancer risk in a Japanese population...
March 18, 2019: Carcinogenesis
Divya Bhagirath, Thao Ly Yang, Z Laura Tabatabai, Varahram Shahryari, Shahana Majid, Rajvir Dahiya, Yuichiro Tanaka, Sharanjot Saini
The prostate cancer (PCa) genome is characterized by deletions of chromosome 8p21-22 region that increase significantly with tumor grade and are associated with poor prognosis. We proposed and validated a novel, paradigm shifting hypothesis that this region is associated with a set of microRNA genes - miRs-3622, -3622b, -383- that are lost in PCa and play important mechanistic roles in PCa progression and metastasis. Extending our hypothesis, in this study, we evaluated the role of a microRNA gene located in chr8p- miR-4288- by employing clinical samples and cell lines...
March 15, 2019: Carcinogenesis
Nalini Srinivas, Sivaramakrishna Rachakonda, Thomas Hielscher, Silvia Calderazzo, Peter Rudnai, Eugen Gurzau, Kvetoslava Koppova, Tony Fletcher, Rajiv Kumar
Telomere length per se a heritable trait has been reported to be associated with different diseases including cancers. In this study based on arsenic exposed 528 cases with basal cell carcinoma of skin (BCC) and 533 healthy controls we investigated effect of telomere length, measured by real-time PCR, on the disease risk. We observed a statistically significant association between decreased telomere length and increased BCC risk (OR = 5.92, 95% CI = 3.92-9.01, P<0.0001). Due to confounder effect of arsenic exposure, in a two-sample Mendelian randomization (MR), telomere-length associated single nucleotide polymorphisms as instrument variables violated valid assumptions; however, one-sample MR adjusted for arsenic exposure indicated an increased risk of BCC with short telomeres...
March 15, 2019: Carcinogenesis
Junfeng Xu, Chia-Wen Tsai, Wen-Shin Chang, Yuyan Han, Da-Tian Bau, Curtis A Pettaway, Jian Gu
Global DNA methylation may play important roles in cancer etiology and prognosis. The goal of this study is to investigate whether the methylation of long interspersed nucleotide elements (LINE-1) and subtelomeric DNA repeats D4Z4 in leukocyte DNA is associated with aggressive prostate cancer (PCa) in African Americans. We measured DNA methylation levels of LINE-1 and D4Z4 in 306 AA PCa patients using pyrosequencing and compared their methylation levels among clinical variables. We further applied multivariate Cox proportional hazards model and Kaplan-Meier survival function and log-rank tests to assess the association between DNA methylation and biochemical recurrence (BCR)...
March 15, 2019: Carcinogenesis
Ingrid Elisia, Brandon Cho, Mariah Hay, Michael Yu Li, Elyse Hofs, Vivian Lam, Roger A Dyer, Julian Lum, Gerald Krystal
In previous studies we found that low carbohydrate (CHO) diets reduced the incidence of tumors in mice genetically predisposed to cancer. However, since more than 90% of human cancers arise via carcinogen-induced somatic mutations we investigated, herein, the role that different types and levels of CHO, protein and lipid play in lung cancer induced by the tobacco-specific carcinogen, nicotine-derived nitrosamine ketone (NNK) in A/J mice. We found lowering CHO levels significantly reduced lung nodules and blood glucose levels...
March 15, 2019: Carcinogenesis
Jinjie Wu, Haiyan Li, Hongyu Xie, Xianrui Wu, Ping Lan
Colorectal cancer (CRC) is a complex and heterogeneous malignant cancer characterized by its high prevalence and poor prognosis. Among different etiologies, impairment of immune surveillance and dysbiosis are important events to mediate the invasion and metastasis of CRC. Although aberrant distribution of macrophages and microbiota exhibits distinct properties to modulate the malignant behaviors of CRC, the crosstalk among macrophages, microbiomes and tumor cells remains unclear. Exosomes are intercellular messengers carrying different cargo to regulate the biological and pathologic changes of recipient cells...
March 13, 2019: Carcinogenesis
Bin Ma, Peter W Villalta, J Bradley Hochalter, Irina Stepanov, Stephen S Hecht
The formation of methyl DNA adducts is a critical step in carcinogenesis initiated by exposure to methylating carcinogens. Methyl DNA phosphate adducts, formed by methylation of the oxygen atoms of the DNA phosphate backbone, have been detected in animals treated with methylating carcinogens. However, detection of these adducts in human tissues has not been reported. We developed an ultrasensitive liquid chromatography-nanoelectrospray ionization-high resolution tandem mass spectrometry method for detecting methyl DNA phosphate adducts...
March 12, 2019: Carcinogenesis
H Dean Hosgood, Wei Hu, Nathaniel Rothman, Madelyn Klugman, Stephanie J Weinstein, Jarmo Virtamo, Demetrius Albanes, Richard Cawthon, Qing Lan
Disruption of ribosomal DNA (rDNA) has been linked to a variety of diseases in humans, including carcinogenesis. To evaluate the associations between rDNA copy number (CN) and risk of lung cancer, we measured 5.8S and 18S rDNA CN in the peripheral blood of 229 incident lung cancer cases and 1:1 matched controls from a nested case-control study within a prospective cohort of male smokers. There was a dose-response relationship between quartiles of both 18S and 5.8S rDNA CN and risk of lung cancer (odds ratio [OR], 95% confidence interval [CI]: 18S: 1...
March 12, 2019: Carcinogenesis
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