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Molecular Carcinogenesis

Xiaomin Fu, Jizhen Lin, Fujun Qin, Zihe Yang, Yuechao Ding, Yong Zhang, Lu Han, Xiaoyan Zhu, Qinxian Zhang
Liver tumor initiating cells (TICs), a small subset cells in tumor bulk, are responsible for liver tumor initiation, metastasis and relapse. However, the regulatory mechanism of liver TICs remains largely unknown. Here we found a long noncoding RNA lncAPC, locating near from APC locus, was highly expressed in liver cancer and liver TICs. LncAPC was required for liver TIC self-renewal. Silencing and overexpressing lncAPC showed impaired and enhanced sphere formation capacity of liver TICs, respectively. By recruiting EZH2 to APC promoter, LncAPC inhibits APC transcription and thus drives the activation of Wnt/β-catenin signaling...
November 16, 2017: Molecular Carcinogenesis
Lawei Yang, Ziying Lin, Yahong Wang, Shenglan Gao, Qinglan Li, Chunyan Li, Wenya Xu, Jie Chen, Tie Liu, Zeqing Song, Gang Liu
Cisplatin-based chemotherapy is the most commonly used treatment regimen for lung cancer. Cancer stem cells (CSCs) are postulated to be important promoters of drug resistance. We previously found that miR-5100 is overexpressed in lung cancer, but it is unknown whether and how miR-5100 regulates cisplatin resistance. Here, we demonstrated that miR-5100 was significantly up-regulated in CD44 + CD133+ lung cancer stem cells (LCSCs) compared with non-CSCs. Additionally, over-expression of miR-5100 increased CSC properties, cell growth and tumor sphere formation in lung cancer cell line A549 or H1299, and that miR-5100 inhibitor significantly increased sensitivity of LCSCs to cisplatin in vitro...
November 16, 2017: Molecular Carcinogenesis
Shanshan Wang, Haibo Han, Ying Hu, Wei Yang, Yunwei Lv, Limin Wang, Lianhai Zhang, Jiafu Ji
MiR-130a-3p was found to play tumor suppressor role in most human cancers, except for gastric cancer. However, in this study, we demonstrated that miR-130a-3p was significantly down-regulated in gastric carcinoma (GC) tissues compared with adjacent non-neoplastic tissues, and decreased miR-130a-3p expression was associated with shorter overall survival (OS) and was an independent prognostic factor for OS in GC patients. Over-expression of miR-130a-3p remarkably inhibited not only GC cell migration, invasion, and epithelial-mesenchymal transition (EMT) in vitro, but also tumorigenesis and lung metastasis in the chick embryo chorioallantoic membrane (CAM) assay in vivo...
November 1, 2017: Molecular Carcinogenesis
Vinay Koshy Varghese, Vaibhav Shukla, Shama Prasada Kabekkodu, Deeksha Pandey, Kapaettu Satyamoorthy
Regulation of miRNA gene expression by DNA promoter methylation may represent a key mechanism to drive cervical cancer progression. In order to understand the impact of DNA promoter methylation on miRNAs at various stages of cervical carcinogenesis, we performed DNA methylation microarray on Normal Cervical Epithelium (NCE), Cervical Intraepithelial Neoplasia (CIN I - III) and Squamous Cell Carcinoma (SCC) tissues to identify differentially methylated miRNAs followed by validation by bisulfite sequencing. Further, expression of miRNAs was analyzed by qRT-PCR in clinical tissues and cervical cancer cell lines...
October 27, 2017: Molecular Carcinogenesis
Syed S Islam, Ibtehaj Al-Sharif, Ahlam Sultan, Amer Al-Mazrou, Adnane Remmal, Abdelilah Aboussekhra
Triple-negative breast tumors are very aggressive and contain relatively high proportion of cancer stem cells, and resistant to chemotherapeutic drugs including cisplatin. To overcome these limitations, we combined eugenol, a natural polyphenolic molecule with cisplatin to normalize cisplatin mediated toxicity and potential drug resistance. Interestingly, the combination treatment provided significantly greater cytotoxic and pro-apoptotic effects as compared to treatment with eugenol or cisplatin alone on several triple-negative breast cancer cells both in vitro and in vivo...
October 26, 2017: Molecular Carcinogenesis
Zhongming Lu, Erich M Sturgis, Lijun Zhu, Hua Zhang, Ye Tao, Peng Wei, Qingyi Wei, Guojun Li
Given the crucial role of Mouse double minute 4 (MDM4) oncoprotein in p53 pathway, single nucleotide polymorphisms (SNPs) could serve as such biomarkers for prediction of SCCOP recurrence. Thus, we investigated associations between three tagging putatively functional variants of MDM4, two in the 3' untranslated region of 3' UTR [rs11801299 (NC_000001.10:g.204529084G>A) and rs10900598(NC_000001.10:g.204525568G>T)] and one in intron 1 [rs1380576(NC_000001.10:g.204488278G>C)], and recurrence risk of SCCOP in 1,008 incident patients...
October 26, 2017: Molecular Carcinogenesis
Carlo Follo, Yao Cheng, William G Richards, Raphael Bueno, Virginia Courtney Broaddus
The benefits of inhibiting autophagy in cancer are still controversial, with differences in outcome based on the type of tumor, the context and the particular stage of inhibition. Here, we investigated the impact of inhibiting autophagy at different stages on chemosensitivity using 3-dimensional (3D) models of mesothelioma, including ex vivo human tumor fragment spheroids. As shown by LC3B accumulation, we successfully inhibited autophagy using either an early stage ULK1/2 inhibitor (MRT 68921) or a late stage inhibitor (hydroxychloroquine)...
October 26, 2017: Molecular Carcinogenesis
María Conde-Rioll, Consuelo Gajate, José J Fernández, Janny A Villa-Pulgarin, José G Napolitano, Manuel Norte, Faustino Mollinedo
Consumption of Brassica (Cruciferae) vegetables is associated with a reduced risk of cancer, but identification of the active components and insights into the underlying molecular events are scarce. Here we found that an extract of Lepidium latifolium, a cruciferous plant native to southern Europe, Mediterranean countries and Asia, showed in vitro cytotoxic activity, inducing caspase-dependent apoptosis, in a variety of human tumor cells, and the plant juice showed in vivo antitumor activity in a HT-29 human colon cancer xenograft mouse model...
October 26, 2017: Molecular Carcinogenesis
Yun Feng, Yanru Wang, Hongliang Liu, Zhensheng Liu, Coleman Mills, Kouros Owzar, Jichun Xie, Younghun Han, David C Qian, Rayjean J Hung Rj, Yonathan Brhane, John McLaughlin, Paul Brennan, Heike Bickeböller, Albert Rosenberger, Richard S Houlston, Neil Caporaso, Maria Teresa Landi, Irene Brüske, Angela Risch, Yuanqing Ye, Xifeng Wu, David C Christiani, Christopher I Amos, Qingyi Wei
The P38MAPK pathway participates in regulating cell cycle, inflammation, development, cell death, cell differentiation, and tumorigenesis. Genetic variants of some genes in the P38MAPK pathway are reportedly associated with lung cancer risk. To substantiate this finding, we used six genome-wide association studies (GWASs) to comprehensively investigate the associations of 14,904 single nucleotide polymorphisms (SNPs) in 108 genes of this pathway with lung cancer risk. We identified six significant lung cancer risk-associated SNPs in two genes (CSNK2B and ZAK) after correction for multiple comparisons by a false discovery rate (FDR) < 0...
October 26, 2017: Molecular Carcinogenesis
Tianhao Sun, Kelvin S C Cheung, Zhi-Li Liu, Frankie Leung, William W Lu
Osteosarcoma (OS) is the most common malignant tumor that develops in bone. Its mortality is very high. Therefore, study of mechanisms of pathogenesis of the OS is urgently required. Previous studies of microarray showed that the expression levels of matrix metallopeptidase 9 (MMP-9) altered significantly in OS. In addition, overexpression of MMP-9 is recognized as an indicator in cancer. However, the exact roles of MMP-9 in OS are not fully investigated. Thus, we firstly studied the roles of MMP-9 in OS and revealed that silence of MMP-9 inhibited OS cell proliferation as determined by MTT assay and colony formation assay...
October 25, 2017: Molecular Carcinogenesis
Martha L Slattery, Lila E Mullany, Lori C Sakoda, Roger K Wolff, John R Stevens, Wade S Samowitz, Jennifer S Herrick
The PI3K/AKT-signaling pathway is one of the most frequently activated signal-transduction pathways in cancer. We examined how dysregulated gene expression is associated with miRNA expression in this pathway in colorectal cancer (CRC). We used data from 217 CRC cases to evaluate differential pathway gene expression between paired carcinoma and normal mucosa and identify miRNAs that are associated with these genes. Gene expression data from RNA-Seq and miRNA expression data from Agilent Human miRNA Microarray V19...
October 25, 2017: Molecular Carcinogenesis
Zihua Pan, Li Liu, Wenjing Nie, Sinead Miggin, Fuman Qiu, Yi Cao, Jinbin Chen, Binyao Yang, Yifeng Zhou, Jiachun Lu, Lei Yang
BACKGROUND: Little is known about long non-coding RNA (lncRNA) related to innate immunity in lung cancer. The advanced glycosylation end-product specific receptor (AGER) belongs to the immunoglobulin superfamily, and currently, is the only innate immune pattern-recognition receptor whose abnormal expression has been detected in lung cancer. We aimed to explore the lncRNA that is related to AGER and test its effect on lung carcinogenesis. METHODS: We selected one lncRNA whose chromosome location is in close proximity to AGER namely lnc-AGER-1 (defined as lncAGER)...
October 25, 2017: Molecular Carcinogenesis
Chun Yan Wang, Su Tang Guo, Amanda Croft, Xu Guang Yan, Lei Jin, Xu Dong Zhang, Chen Chen Jiang
Past studies have shown that mutant KRAS colon cancer cells are susceptible to apoptosis induced by the HSP90 inhibitor AUY922. Nevertheless, intrinsic and acquired resistance remains an obstacle for the potential application of the inhibitor in the treatment of the disease. Here we report that Mcl-1 is important for survival of colon cancer cells in the presence of AUY922. Mcl-1 was upregulated in mutant KRAS colon cancer cells selected for resistance to AUY922-induced apoptosis. This was due to its increased stability mediated by Bcl-2-associated athanogene domain 3 (BAG3), which was also increased in resistant colon cancer cells by heat shock factor 1 (HSF1) as a result of chronic endoplasmic reticulum (ER) stress...
October 25, 2017: Molecular Carcinogenesis
Danilo Ranieri, Benedetta Rosato, Monica Nanni, Francesca Belleudi, Maria Rosaria Torrisi
The altered isoform switching of the fibroblast growth factor receptor 2 (FGFR2) and aberrant expression of the mesenchymal FGFR2c isoform in epithelial cells is involved in cancer progression. We have recently described that the ectopic expression of FGFR2c in normal human keratinocytes induces epithelial-mesenchymal transition and leads to invasiveness and anchorage-independent growth. Here we extended our analysis to the effects of this FGFR2c forced expression on human keratinocyte differentiation and stratification...
October 25, 2017: Molecular Carcinogenesis
Bin Zhang, Chao Deng, Lei Wang, Fan Zhou, Shu Zhang, Wei Kang, Ping Zhan, Juan Chen, Shanshan Shen, Huimin Guo, Ming Zhang, Yi Wang, Feng Zhang, Wei Zhang, Jiangqiang Xiao, Bo Kong, Helmut Friess, Yuzheng Zhuge, Hongli Yan, Xiaoping Zou
Hepatocellular carcinoma (HCC) is the most common type of liver cancer and represents a highly malignant tumor with a poor prognosis. Therapeutic modalities for HCC are limited and generally ineffective. UBE2Q1 is a putative E2 ubiquitin conjugating enzyme, and has been shown to be overexpressed in various types of cancers including HCC. How UBE2Q1 contributes to hepatocarcinogenesis remains unknown. Here, we show that UBE2Q1 is up-regulated in HCC cell lines and in a subset of human HCC tissues. Up-regulation of UBE2Q1 in primary HCC tumors was significantly correlated with shorter overall survival and disease-free survival...
October 13, 2017: Molecular Carcinogenesis
Untack Cho, Boyun Kim, Soochi Kim, Youngjin Han, Yong Sang Song
Obesity is a serious health problem and critically related to poor prognosis in cancer, presumably through induction of chronic inflammation. The major culprit for cancer progression in obesity is presumed to be macrophages. Accumulation of macrophages in adipose tissue due to obesity induced chronic inflammation has been observed. However, obesity-induced macrophage accumulation related to ovarian cancer progression remains unclear. So, the role of macrophage in cancer progression is needed to be further defined for therapeutic intervention...
October 12, 2017: Molecular Carcinogenesis
Shuo Chen, Li-Li Wang, Kai-Xuan Sun, Yin-Ling Xiu, Zhi-Hong Zong, Xi Chen, Yang Zhao
As one of the most frequently diagnosed cancers in women, the development and progression of epithelial ovarian carcinoma (EOC) remains an open area of research. The role of long non-coding RNAs (lncRNAs) in EOC is an emerging field of study. We found that LncRNA TDRG1 (human testis development-related gene 1) was highly expressed in EOC tissues than in normal ovarian tissues, and expression differed significantly with differentiation. LncRNA TDRG1 downregulation suppressed EOC cell proliferation, migration, and invasion, while its overexpression had the opposite effect...
October 6, 2017: Molecular Carcinogenesis
Tomoyo Kawakubo-Yasukochi, Masahiko Morioka, Mai Hazekawa, Atsushi Yasukochi, Takuya Nishinakagawa, Kazuhiko Ono, Shintaro Kawano, Seiji Nakamura, Manabu Nakashima
Oral squamous cell carcinoma (OSCC) constitutes over 90% of all cancers in the oral cavity. The prognosis for patients with invasive OSCC is poor; therefore, it is important to understand the molecular mechanisms of invasion and subsequent metastasis not only to prevent cancer progression but also to detect new therapeutic targets against OSCC. Recently, extracellular vesicles-particularly exosomes-have been recognized as intercellular communicators in the tumor microenvironment. As exosomic cargo, deregulated microRNAs (miRNAs) can shape the surrounding microenvironment in a cancer-dependent manner...
October 5, 2017: Molecular Carcinogenesis
Shasha Tao, Montserrat Rojo de la Vega, Eli Chapman, Aikseng Ooi, Donna D Zhang
Targeting the transcription factor NRF2 has been recognized as a feasible strategy for cancer prevention and treatment, but many of the mechanistic details underlying its role in cancer development and progression are lacking. Therefore, careful mechanistic studies of the NRF2 pathway in cancer initiation and progression are needed to identify which therapeutic avenue-activation or inhibition-is appropriate in a given context. Moreover, while numerous reports confirm the protective effect of NRF2 activation against chemical carcinogenesis little is known of its role in cancer arising from spontaneous mutations...
October 4, 2017: Molecular Carcinogenesis
Wenhua Zhao, Fengqiang Shi, Zhikun Guo, Jiaojie Zhao, Xueying Song, Hua Yang
Autophagy is an evolutionarily conserved pathway in which cytoplasmic contents are degraded and recycled. This study found that submicromolar concentrations of urolithin A, a major polyphenol metabolite, induced autophagy in SW620 colorectal cancer (CRC) cells. Exposure to urolithin A also dose-dependently decreased cell proliferation, delayed cell migration and decreased matrix metalloproteinas-9 (MMP-9) activity. In addition, inhibition of autophagy by Atg5-siRNA, caspases by Z-VAD-FMK suppressed urolithin A- stimulated cell death and anti-metastatic effects...
October 4, 2017: Molecular Carcinogenesis
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