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Sarah F Andres, Kathy N Williams, Jacqueline B Plesset, Jeffrey J Headd, Rei Mizuno, Priya Chatterji, Ashley A Lento, Andres J Klein-Szanto, Rosemarie Mick, Kathryn E Hamilton, Anil K Rustgi
The RNA binding protein insulin-like growth factor 2 mRNA binding protein 1 (IMP1) is overexpressed in colorectal cancer (CRC); however, evidence for a direct role for IMP1 in CRC metastasis is lacking. IMP1 is regulated by let-7 microRNA, which binds in the 3' untranslated region (UTR) of the transcript. The availability of binding sites is in part controlled by alternative polyadenylation (APA), which determines 3' UTR length. Expression of the short 3' UTR transcript (lacking all miRNA sites) results in higher protein levels and is correlated with increased proliferation...
November 8, 2018: Carcinogenesis
Huijie Cui, Mingshuang Tang, Min Zhang, Shanshan Liu, Siyu Chen, Ziqian Zeng, Zhuozhi Shen, Bin Song, Jiachun Lu, Hong Jia, Dongqing Gu, Ben Zhang
Variants in the PSCA gene have been linked with risk of multiple cancers and other diseases. But results have been inconclusive and no systematic research synopsis has been available. We did a comprehensive meta-analysis to investigate associations between variants in this gene and risk of nine cancers and four non-neoplastic diseases based on data from 55 publications including 81 961 cases and 442 932 controls. We graded levels of cumulative epidemiological evidence of a significant association using the Venice criteria and false-positive report probability tests...
November 8, 2018: Carcinogenesis
Joseph L Sottnik, Vandana Mallaredy, Ana Chauca-Diaz, Carolyn Ritterson Lew, Charles Owens, Garrett M Dancik, Serena Pagliarani, Sabrina Lucchiari, Maurizio Moggio, Michela Ripolone, Giacomo P Comi, Henry F Frierson, David Clouthier, Dan Theodorescu
Amylo-α-1,6-glucosidase,4-α-glucanotransferase (AGL) is an enzyme primarily responsible for glycogen debranching. Germline mutations lead to glycogen storage disease type III (GSDIII). We recently found AGL to be a tumor suppressor in xenograft models of human bladder cancer (BC) and low levels of AGL expression in BC are associated with poor patient prognosis. However, the impact of low AGL expression on the susceptibility of normal bladder to carcinogenesis is unknown. We address this gap by developing a germline Agl knockout (Agl-/-) mouse that recapitulates biochemical and histological features of GSDIII...
November 7, 2018: Carcinogenesis
Santanu Maji, Omprakash Shriwas, Sabindra K Samal, Manashi Priyadarshini, Rachna Rath, Sanjay Panda, Saroj Kumar Das Majumdar, Dillip Kumar Muduly, Rupesh Dash
Cisplatin alone or in combination with 5FU (5-fluorouracil) and docetaxel (TPF) are common regimen chemotherapeutics for treatment of advanced oral squamous cell carcinoma (OSCC). Despite the initial positive response, several patients experience relapse due to chemoresistance. The potential role of Bcl-2 antiapoptotic members in acquired chemoresistance is yet to be explored. To address this, we designed two different relevant OSCC chemoresistant models: (i) acquired chemoresistant cells, where OSCC lines were treated with conventional chemotherapy for a prolonged period to develop chemoresistance, and (ii) chemoresistant patient-derived cells, where primary cells were established from tumor of neoadjuvant-treated OSCC patients who do not respond to TPF...
November 3, 2018: Carcinogenesis
Maarit Koivisto, Minna Tervahartiala, István Kenessey, Sirpa Jalkanen, Peter J Boström, Marko Salmi
CD73 is an adenosine-producing cell surface enzyme, which exerts strong anti-inflammatory and migration modulating effects in many cell types. We evaluated the potential of CD73 as a biomarker in predicting the outcome of bladder carcinoma. CD73 expression in tumor and stromal cells was analyzed using immunohistochemistry in 270 bladder cancer patients (166 non-muscle invasive bladder cancer (NMIBC) and 104 muscle invasive bladder cancer (MIBC) tumors). The correlations of CD73 with clinical and pathological characteristics were evaluated with Pearson's and Fischer's tests...
November 3, 2018: Carcinogenesis
Wei Zhan, Xin Liao, Yuan Wang, Lianghe Li, Jin Li, Zhongsheng Chen, Tian Tian, Jingdong He
Colon tumor is a conman tumor in the world. There are kinds of cells in colon tumor bulk, and only a small population can initiate tumor efficiently and termed as tumor initiating cells (TICs). With self-renewal and differentiation capacities, colon TICs drive colon tumorigenesis, metastasis and relapse. However, the molecular mechanisms of colon TICs self-renewal are elusive. Here, we found a circular RNA (circCTIC1) was highly expressed in colon tumor and colon TICs. circCTIC1 knockdown impaired the self-renewal of colon TICs, and its overexpression played an opposite role...
November 2, 2018: Carcinogenesis
Victoria Neumeyer, Martina Grandl, Alisa Dietl, Anna Brutau-Abia, Michael Allgäuer, Behnam Kalali, Yang Zhang, Kai-Feng Pan, Katja Steiger, Michael Vieth, Martina Anton, Raquel Mejías-Luque, Markus Gerhard
Ring Finger Protein 43 (RNF43) is an E3 ubiquitin ligase that has been described to be frequently mutated in gastrointestinal cancers. RNF43 downregulation was associated with distant metastasis, TNM stage and poorer survival in patients with gastric and colorectal cancers. Functional analysis has shown that overexpressed RNF43 negatively regulates Wnt signaling by ubiquitinating Frizzled receptors and targeting them for degradation, and by sequestering T-cell factor 4 (TCF4) to the nuclear membrane, thereby inhibiting Wnt-mediated transcription...
October 31, 2018: Carcinogenesis
Chunmei Fan, Jinpeng Wang, Yanyan Tang, Yian Wang, Fang Xiong, Shanshan Zhang, Xiayu Li, Bo Xiang, Xu Wu, Can Guo, Jian Ma, Ming Zhou, Xiaoling Li, Wei Xiong, Yong Li, Guiyuan Li, Zhaoyang Zeng
Nasopharyngeal carcinoma (NPC) is a unique malignant cancer with high metastasis. Because the early symptoms of NPC patients are not obvious, most patients have distant metastases when diagnosed, which makes treatment difficult. Long noncoding RNAs (lncRNAs) are emerging as important regulators in human carcinogenesis. LncRNAs have been increasingly identified, but remain largely unknown in NPC. Therefore, we performed gene expression profiling to screen for altered expression of lncRNAs in NPC tissues and adjacent samples...
October 30, 2018: Carcinogenesis
Chuxiao Zhang, Pengbo Cao, Aiqing Yang, Xia Xia, Yuanfeng Li, Mengting Shi, Ying Yang, Xiaojun Wei, Chun Yang, Gangqiao Zhou
Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related mortality worldwide. Genomic copy number deletion at chromosome 14q31.1-32.13 was frequently observed in HCC; however, the relevant functional target(s) at that locus is not well determined. Here, we performed integrative genomic analyses and identified zinc finger CCCH-type containing 14 (ZC3H14) as a promising candidate at 14q31.1-32.13. We observed frequent copy number deletion (17.1%) and down-regulation of ZC3H14 in primary HCC tissues...
October 29, 2018: Carcinogenesis
Ya-Kai Huang, Wei-Ming Kang, Zhi-Qiang Ma, Yu-Qin Liu, Li Zhou, Jian-Chun Yu
The effects of nuclear ubiquitous casein and cyclin-dependent kinase substrate 1 (NUCKS1) on tumor cells and the relevant mechanisms are less well defined. This study aimed to explore the role and mechanism of action of NUCKS1 in gastric cancer (GC) progression. The expression dynamics of NUCKS1 were examined using microarray-based immunohistochemistry in a group of carcinomatous and adjacent non-tumor specimens. Various in vitro and in vivo assays were performed to clarify the function of NUCKS1 in GC and its underlying mechanisms...
October 29, 2018: Carcinogenesis
Donghui Cao, Yanhua Wu, Zhifang Jia, Dan Zhao, Yangyu Zhang, Tianyu Zhou, Menghui Wu, Houjun Zhang, Tetsuya Tsukamoto, Masanobu Oshima, Jing Jiang, Xueyuan Cao
The natural phenolic substance, 18β-glycyrrhetinic acid (GRA), has shown enormous potential in the chemoprevention of cancers with rich resources and biological safety, but the GRA-regulated genetic and epigenetic profiles are unclear. Deregulated mitochondrial cellular energetics supporting higher ATP provisions relative to the uncontrolled proliferation of cancer cells is a cancer hallmark. The Toll-like receptor 2 (TLR2) signaling pathway has emerged as a key molecular component in gastric cancer (GC) cell proliferation and epithelial homeostasis...
October 26, 2018: Carcinogenesis
Emmanouil Papasavvas, Andrew V Kossenkov, Livio Azzoni, Nicola M Zetola, Agnieszka Mackiewicz, Brian N Ross, Matthew Fair, Surya Vadrevu, Doreen Ramogola-Masire, Ian Sanne, Cynthia Firnhaber, Luis J Montaner
Identification of factors associated with human papillomavirus (HPV) cervical histopathology or recurrence/relapse following loop electrosurgical excision procedure (LEEP) would allow for better management of the disease. We investigated whether gene signatures could: a) associate with HPV cervical histopathology, and b) identify women with post-LEEP disease recurrence/relapse. Gene array analysis was performed on paraffin-embedded cervical tissue-isolated RNA from two cross-sectional cohorts of antiretroviral therapy (ART)-suppressed HIV+HPV+ co-infected women: a) 55 women in South Africa recruited into three groups: High risk (HR) (-) (n=16) and HR (+) (n=15) HPV without cervical histopathology, and HR (+) HPV with Cervical Intraepithelial Neoplasia (CIN) grade 1/2/3 (n=24); b) 28 women in Botswana with CIN2/3 treated with LEEP 12-month prior to recruitment and presenting with (n=13) and without (n=15) lesion recurrence/relapse (tissue was analyzed at first LEEP)...
October 26, 2018: Carcinogenesis
Narayanasamy Badrinath, So Young Yoo
Mitochondria play pivotal roles in most eukaryotic cells, ranging from energy production to regulation of apoptosis. As sites of cellular respiration, mitochondria experience accumulation of reactive oxygen species (ROS) due to damage in electron transport chain carriers. Mutations in mitochondrial DNA (mtDNA) as well as nuclear DNA (nDNA) are reported in various cancers. Mitochondria have a dual role in cancer: the development of tumors due to mutations in mitochondrial genome and the generation of ROS. Impairment in the mitochondria-regulated apoptosis pathway accelerates tumorigenesis...
October 24, 2018: Carcinogenesis
Tommaso A Dragani, Francesca Colombo, Elizabeth N Pavlisko, Victor L Roggli
No abstract text is available yet for this article.
October 23, 2018: Carcinogenesis
Zhaohui Chen, Lijie Zhou, Liang Chen, Ming Xiong, Gallina Kazobinka, Zili Pang, Teng Hou
R-Spondin 3 (RSPO3) is a secreted protein that associates directly with Wnt/β-catenin signaling. However, its functional contribution and prognostic value in human bladder cancer remain unclear. Here, we showed that RSPO3 is upregulated in bladder cancer tissues and cells, and high expression of RSPO3 correlates with advanced clinicopathological features, poor prognosis and disease progression in bladder cancer patients. Furthermore, we observed that ectopic expression or knockdown of RSPO3 profoundly promoted or inhibited, respectively, the invasive ability of bladder cancer cells...
October 17, 2018: Carcinogenesis
Pengyu Liu, Wanlu Cao, Buyun Ma, Meng Li, Kan Chen, Kostandinos Sideras, Jan-Willem Duitman, Dave Sprengers, T C Khe Tran, Jan N M Ijzermans, Katharina Biermann, Joanne Verheij, C Arnold Spek, Jaap Kwekkeboom, Qiuwei Pan, Maikel P Peppelenbosch
CCAAT/enhancer-binding protein delta (CEBPD) is associated with the regulation of apoptosis and cell proliferation and is a candidate tumor suppressor gene. Here, we investigated its role in hepatocellular carcinoma (HCC). We observe that CEBPD mRNA expression is significantly downregulated in HCC tumors as compared with adjacent tissues. Protein levels of CEBPD are also lower in tumors relative to adjacent tissues. Reduced expression of CEBPD in the tumor correlates with worse clinical outcome. In both Huh7 and HepG2 cells, shRNA-mediated CEBPD knockdown significantly reduces cell proliferation, single cell colony formation and arrests cells in the G0/G1 phase...
October 16, 2018: Carcinogenesis
Kim B Pedersen, Casey F Pulliam, Aarshvi Patel, Fabio Del Piero, Tatiane T N Watanabe, Umesh D Wankhade, Kartik Shankar, Chindo Hicks, Martin J Ronis
Liver cancer results in a high degree of mortality, especially among men. Since fatty liver disease is a risk factor for development of hepatocellular carcinoma, we investigated the role of dietary fat type in tumor promotion by high fat diets in mice after initiation with the chemical carcinogen diethyl nitrosamine. Tumor incidence and multiplicity was significantly greater in males than in females. In males, fat type had complex effects on tumorigenesis. Preneoplastic foci were most prevalent in mice fed a polyunsaturated fat diet enriched in docosahexaenoic acid (DHA), while carcinomas and large visible liver tumors were significantly greater in mice fed a saturated fat diet made with cocoa butter relative to mice fed mono- or polyunsaturated fats...
October 16, 2018: Carcinogenesis
Zhihong Gong, Jie Wang, Dan Wang, Matthew F Buas, Xuefeng Ren, Jo Freudenheim, Steven A Belinsky, Song Liu, Christine B Ambrosone, Michael J Higgins
Breast cancer is a heterogeneous disease, characterized by molecularly and phenotypically distinct tumor subtypes, linked to disparate clinical outcomes. American women of African ancestry (AA) are more likely than those of European ancestry (EA) to be diagnosed with aggressive, estrogen receptor negative (ER-) or triple negative (TN) breast cancer, and to die of this disease. However, the underlying causes of AA predisposition to ER-/TN breast cancer are still largely unknown. In this study, we performed high-throughput whole-genome miRNA expression profiling in breast tissue samples from both AA and EA women...
October 13, 2018: Carcinogenesis
Shengnan Hao, Xi Chen, Fang Wang, Qianqian Shao, Jia Liu, Hui Zhao, Chao Yuan, Hanxiao Ren, Haiting Mao
Interleukin 35 (IL-35) is a potent immunosuppressive cytokine, consisting of an EBV-induced gene 3 (EBI3) subunit and a p35 subunit. IL-35 is mainly produced by regulatory T and regulatory B cells and plays a crucial role in the development and prevention of infectious and autoimmune diseases. However, the effect of IL-35 in malignant disease is not well understood. In this study, we demonstrated that breast cancer cells (BCCs) also expressed and secreted IL-35 and higher level of IL-35 in BCCs was closely associated with poor prognosis of patients and was an independent unfavorable prognostic factor for breast cancer...
October 13, 2018: Carcinogenesis
Jialin Xiao, Pinchas Cohen, Mariana Carla Stern, Folakemi Odedina, John Carpten, Renee Reams
Prostate cancer remains the second most prevalent cancer in men. Its incidence, progression and mortality profiles vary significantly by race and ethnicity, with African-American men having the highest incidence rate and mortality rate in the world. Although these disparities can be partially explained by socioeconomic factors, the underlying molecular causes are complex and require careful research. A considerable amount of literature exists, supporting the association between mitochondrial health and the incidence, aggression and risk of prostate cancer...
October 9, 2018: Carcinogenesis
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