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Molecular Carcinogenesis

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https://www.readbyqxmd.com/read/29350431/mifast-a-novel-and-rapid-microrna-target-capture-method
#1
Ashley M Poenitzsch Strong, Scott M Berry, David J Beebe, Jian-Liang Li, Vladimir S Spiegelman
MicroRNAs (miRNAs), small 22-25 nucleotide non-coding RNAs, play important roles in cellular and tumor biology. However, characterizing miRNA function remains challenging due to an abundance of predicted targets and an experimental bottleneck in identifying biologically relevant direct targets. Here we developed a novel technique (miFAST) to identify direct miRNA target genes. Using miFAST, we confirmed several previously reported miR-340 target genes and identified five additional novel direct miR-340 targets in melanoma cells...
January 19, 2018: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/29323757/differentiation-associated-urothelial-cytochrome-p450-oxidoreductase-predicates-the-xenobiotic-metabolising-activity-of-luminal-muscle-invasive-bladder-cancers
#2
Simon C Baker, Volker M Arlt, Radek Indra, Madeleine Joel, Marie Stiborova, Ian Eardley, Niaz Ahmad, Wolfgang Otto, Maximilian Burger, Peter Rubenwolf, David H Phillips, Jennifer Southgate
Extra-hepatic metabolism of xenobiotics by epithelial tissues has evolved as a self-defence mechanism but has potential to contribute to the local activation of carcinogens. Bladder epithelium (urothelium) is bathed in excreted urinary toxicants and pro-carcinogens. This study reveals how differentiation affects cytochrome P450 (CYP) activity and the role of NADPH:P450 oxidoreductase (POR). CYP1A1 and CYP1B1 transcripts were inducible in normal human urothelial (NHU) cells maintained in both undifferentiated and functional barrier-forming differentiated states in vitro...
January 11, 2018: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/29323753/associations-of-mitochondrial-polymorphisms-with-sporadic-colorectal-adenoma
#3
Bharat Thyagarajan, Weihua Guan, Veronika Fedirko, Helene Barcelo, Ramya Ramasubramaian, Myron Gross, Michael Goodman, Roberd M Bostick
Somatic mutations in mitochondrial DNA have been reported in colorectal adenomatous polyps (adenomas), the precursors to most colorectal cancers. However, there are no reports of associations of germline variation in mitochondrial DNA with adenoma risk. We investigated associations of germline polymorphisms in the displacement loop (D-loop) and non-D-loop region of the mitochondrial genome with incident, sporadic colorectal adenoma in three pooled colonoscopy-based case-control studies (n = 327 adenoma cases, 420 controls) that used identical methods for case and risk factor ascertainment...
January 11, 2018: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/29323748/the-gain-of-function-mutation-e76k-in-shp2-promotes-cac-tumorigenesis-and-induces-emt-via-the-wnt-%C3%AE-catenin-signaling-pathway
#4
Qian Zhang, Rongrong Zhao, Chuling Fan, Xinyi Wang, Youzhi Xu, Yakun Liu, Siying Wang
SHP2 is encoded by the protein tyrosine phosphatase 11 (Ptpn11) gene. Several gain-of-function (GOF) mutations in Ptpn11 have been identified in human hematopoietic malignancies and solid tumors. In addition, the mutation rate for SHP2 is the highest for colorectal cancer (CRC) among solid tumors. The E76K GOF mutation is the most common and active SHP2 mutation; however, the pathogenic effects and function of this mutation in CRC tumor progression have not been well characterized. The Wnt/β-catenin (CTNNB1) signaling pathway is crucial for CRC, and excessive activation of this pathway has been observed in several tumors...
January 11, 2018: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/29318656/circadian-genes-and-risk-of-prostate-cancer-in-the-prostate-cancer-prevention-trial
#5
Lisa W Chu, Cathee Till, Baiyu Yang, Catherine M Tangen, Phyllis J Goodman, Kai Yu, Yong Zhu, Summer Han, Ashraful M Hoque, Christine Ambrosone, Ian Thompson, Robin Leach, Ann W Hsing
Circadian genes have been considered as a possible biological mechanism for the observed relationship between circadian rhythm disruptions and increased risk of hormone-related cancers. In the current study, we investigated the relationship between circadian gene variants and prostate cancer risk and whether reducing bioavailable testosterone modifies the circadian genes-prostate cancer relationship. We conducted a nested case-control study among Caucasian men in the Prostate Cancer Prevention Trial (PCPT), a randomized placebo-controlled clinical trial to assess if finasteride (an androgen bioactivation inhibitor) could prevent prostate cancer...
January 10, 2018: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/29315835/fto-regulates-the-chemo-radiotherapy-resistance-of-cervical-squamous-cell-carcinoma-cscc-by-targeting-%C3%AE-catenin-through-mrna-demethylation
#6
Shun Zhou, Zhou-Lan Bai, Di Xia, Zhi-Jun Zhao, Ren Zhao, Yan-Yang Wang, Hong Zhe
The role of N6 -methyladenosine (m6 A) demethylase Fat Mass and Obesity-associated protein (FTO) in the regulation of chemo-radiotherapy resistance remains largely unknown. Here, we show that the mRNA level of FTO is elevated in cervical squamous cell carcinoma (CSCC) tissues when compared with respective adjacent normal tissues. FTO enhances the chemo-radiotherapy resistance both in vitro and in vivo through regulating expression of β-catenin by reducing m6 A levels in its mRNA transcripts and in turn increases excision repair cross-complementation group 1 (ERCC1) activity...
January 9, 2018: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/29315819/genetic-and-small-molecule-inhibition-of-arylamine-n-acetyltransferase-1-reduces-anchorage-independent-growth-in-human-breast-cancer-cell-line-mda-mb-231
#7
Marcus W Stepp, Mark A Doll, Samantha M Carlisle, J Christopher States, David W Hein
Arylamine N-acetyltransferase 1 (NAT1) expression is reported to affect proliferation, invasiveness, and growth of cancer cells. MDA-MB-231 breast cancer cells were engineered such that NAT1 expression was elevated or suppressed, or treated with a small molecule inhibitor of NAT1. The MDA-MB-231 human breast cancer cell lines were engineered with a scrambled shRNA, a NAT1 specific shRNA or a NAT1 overexpression cassette stably integrated into a single flippase recognition target (FRT) site facilitating incorporation of these different genetic elements into the same genomic location...
January 9, 2018: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/29314290/oncogene-rna-helicase-ddx6-promotes-the-process-of-c-myc-expression-in-gastric-cancer-cells
#8
Kohei Taniguchi, Ayako Iwatsuki, Nobuhiko Sugito, Haruka Shinohara, Yuki Kuranaga, Yuki Oshikawa, Toshihiro Tajirika, Manabu Futamura, Kazuhiro Yoshida, Kazuhisa Uchiyama, Yukihiro Akao
Human DEAD-box RNA helicase gene DDX6 was cloned from B-cell lymphoma cell line RC-K8. Previously, we reported that DDX6 acts as oncogene in several cancers such as colorectal cancer and hepatocellular carcinoma. However, the detailed mechanism of DDX6 action in carcinogenesis is largely unknown. In this study, we examined the functions of DDX6 in clinical gastric cancer (GC) samples and GC cells. DDX6 protein expression levels of cancer samples were higher than those of the adjacent normal tissues in 25 clinical GC samples (median value: 1...
January 4, 2018: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/29280516/suppression-of-stat3-nh2-terminal-domain-chemosensitizes-medulloblastoma-cells-by-activation-of-protein-inhibitor-of-activated-stat3-via-de-repression-by-microrna-21
#9
Sutapa Ray, Don W Coulter, Shawn D Gray, Jason A Sughroue, Shrabasti Roychoudhury, Erin M McIntyre, Nagendra K Chaturvedi, Kishor K Bhakat, Shantaram S Joshi, Timothy R McGuire, John G Sharp
Medulloblastoma (MB) is a malignant pediatric brain tumor with poor prognosis. Signal transducers and activators of transcription-3 (STAT3) is constitutively activated in MB where it functions as an oncoprotein, mediating cancer progression and metastasis. Here, we have delineated the functional role of activated STAT3 in MB, by using a cell permeable STAT3-NH2 terminal domain inhibitor (S3-NTDi) that specifically perturbs the structure/function of STAT3. We have implemented several biochemical experiments using human MB tumor microarray (TMA) and pediatric MB cell lines, derived from high-risk SHH-TP53-mutated and MYC-amplified Non-WNT/SHH tumors...
December 27, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/29278657/inhibition-of-autophagy-potentiates-the-anti-metastasis-effect-of-phenethyl-isothiocyanate-through-jak2-stat3-pathway-in-lung-cancer-cells
#10
Huimin Wang, Limin Wang, Limin Cao, Qicheng Zhang, Qianqian Song, Zhaowei Meng, Xiang Wu, Ke Xu
Phenethyl isothiocyanate (PEITC) is a natural compound abundant in cruciferous vegetables. PEITC possesses anti-tumor effect in various human malignances. Our previous study has shown that benzyl isothiocyanates (BITC) induce autophagy in lung cancer cells. However, whether autophagy play a role in the inhibitory effect of PEITC on lung cancer metastasis is unclear. In this study, we found that PEITC suppressed migration and invasion of lung cancer cells by regulating MMP2. It also induced autophagy, evidenced by the formation of acidic vesicular organelles (AVOs), the punctate pattern of LC3, the accumulation of LC3-II, and the expression of Beclin-1...
December 26, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/29247555/the-triterpenoid-corosolic-acid-blocks-transformation-and-epigenetically-reactivates-nrf2-in-tramp-c1-prostate-cells
#11
Jie Yang, Renyi Wu, Wenji Li, Linbo Gao, Yuqing Yang, Ping Li, Ah-Ng Kong
Corosolic acid (CRA) is found in various plants and has been used as a health food supplement worldwide. Although it has been reported that CRA exhibits significant anticancer activity, the effect of this compound on prostate cancer remains unknown. In this study, we investigated the effect of CRA on cellular transformation and the reactivation of nuclear factor erythroid 2-related factor 2 (Nrf2) through epigenetic regulation in TRAMP-C1 prostate cells. Specifically, we found that CRA inhibited anchorage-independent growth of prostate cancer TRAMP-C1 cells but not Nrf2 knockout prostate cancer TRAMP-C1 cells...
December 16, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/29247548/extracellular-vesicles-as-drivers-of-epithelial-mesenchymal-transition-and-carcinogenic-characteristics-in-normal-prostate-cells
#12
Aline G Souza, Isaura Beatriz B Silva, Esther Campos-Fernández, Karina Marangoni, Victor Alexandre F Bastos, Patrícia T Alves, Luiz R Goulart, Vivian Alonso-Goulart
There is increasing evidence that cancer dissemination and metastasis establishment may not only be due to the movement of tumor cells. Content of extracellular vesicles (EVs) secreted by tumor cells may also reflect the origin of these cells. Some molecules that constitute these EVs have already been used as targets for detection of specific tumors. However, to the best of our knowledge, EVs from biopsies and plasma have not yet been compared nor thoroughly investigated as triggers of malignant transformation and metastatic niche formation...
December 16, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/29240261/mitochondrial-dysfunction-rad51-and-ku80-proteolysis-promote-apoptotic-effects-of-dinaciclib-in-bcl-xl-silenced-cells
#13
Daniel R Premkumar, Esther P Jane, Swetha Thambireddy, Philip A Sutera, Jonathon M Cavaleri, Ian F Pollack
In the present study, we investigated the effect of CDK inhibitors (ribociclib, palbociclib, seliciclib, AZD5438 and dinaciclib) on malignant human glioma cells for cell viability, apoptosis, oxidative stress and mitochondrial function using various assays. None of the CDK inhibitors induced cell death at a clinically relevant concentration. However, low nanomolar concentrations of dinaciclib showed higher cytotoxic activity against Bcl-xL silenced cells in a time- and concentration-dependent manner. This effect was not seen with other CDK inhibitors...
December 14, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/29240260/sohlh1-suppresses-glioblastoma-cell-proliferation-migration-and-invasion-by-inhibition-of-wnt-%C3%AE-catenin-signaling
#14
Xinyu Liu, Qing Gao, Na Zhao, Xiaoli Zhang, Weiwei Cui, Jinhao Sun, Jiang Fu, Jing Hao
Glioblastoma (GBM) is the most aggressive and highly invasive type of astrocytic tumors. Despite advances in diagnosis and therapy, the prognosis and survival time remain poor. Identifying key mediators of tumor cell proliferation, migration and invasion is crucial to the development of new and more effective therapies. In this paper, we report the novel role of Spermatogenesis- and oogenesis- specific basic helix-loop-helix transcription factor1 (Sohlh1) in the inhibition of Wnt/β-catenin signaling and aggressive behaviors in GBM cells...
December 14, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/29240257/altered-expression-of-telomere-associated-genes-in-leukocytes-among-brca1-and-brca2-carriers
#15
Hiromi Tanaka, Elizabeth A Phipps, Ting Wei, Xi Wu, Chirayu Goswami, Yunlong Liu, George W Sledge, Lida Mina, Brittney-Shea Herbert
Telomere dysfunction resulting from telomere shortening and deregulation of shelterin components has been linked to the pathogenesis of age-related disorders, including cancer. Recent evidence suggests that BRCA1/2 (BRCA1 and BRCA2) tumor suppressor gene products play an important role in telomere maintenance. Although telomere shortening has been reported in BRCA1/2 carriers, the direct effects of BRCA1/2 haploinsufficiency on telomere maintenance and predisposition to cancer development are not completely understood...
December 14, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/29240254/nf-%C3%AE%C2%BAb-regulated-mir-155-via-repression-of-qki-contributes-to-the-acquisition-of-csc-like-phenotype-during-the-neoplastic-transformation-of-hepatic-cells-induced-by-arsenite
#16
Chao Chen, Fei Luo, Qianlei Yang, Dapeng Wang, Ping Yang, Junchao Xue, Xiangyu Dai, Xinlu Liu, Hui Xu, Jiachun Lu, Aihua Zhang, Qizhan Liu
Chronic exposure to arsenite can cause various human tumors. For the initiation and recurrence of human liver cancer, the acquisition of CSC-like properties is essential. In various cancers, microRNAs (miRNAs) act as regulators in induction of CSC-like properties. Liver cancers over-express miR-155, but the mechanism relating miR-155 and arsenite-induced liver cancer is unknown. Here, we show that long-term exposure of L-02 cells to arsenite increases miR-155 levels by activation of NF-κB and leads to the acquisition of CSC-like properties...
December 14, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/29230882/molecular-profiling-and-genome-wide-analysis-based-on-somatic-copy-number-alterations-in-advanced-colorectal-cancers
#17
Tamotsu Sugai, Yayoi Takahashi, Makoto Eizuka, Ryo Sugimoto, Yasuko Fujita, Wataru Habano, Kouki Otsuka, Akira Sasaki, Eiichiro Yamamoto, Takayuki Matsumoto, Hiromu Suzuki
To characterize somatic alterations in colorectal cancer (CRC), we conducted a genome-scale analysis of 106 CRC specimens. We assessed comprehensive somatic copy number alterations (SCNAs) in these CRC specimens. In addition, we examined microsatellite instability (MSI; low and high), genetic mutations (KRAS, BRAF, TP53, and PIK3CA), and DNA methylation status (classified into low, intermediate, and high type). We stratified molecular alterations in the CRCs using a hierarchical cluster analysis. The examined CRCs could be categorized into 3 subgroups using hierarchical cluster analysis...
December 12, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/29215754/inhibition-of-jak2-stat3-reduces-tumor-induced-angiogenesis-and-myeloid-derived-suppressor-cells-in-head-and-neck-cancer
#18
Jian-Feng Liu, Wei-Wei Deng, Lei Chen, Yi-Cun Li, Lei Wu, Si-Rui Ma, Wen-Feng Zhang, Lin-Lin Bu, Zhi-Jun Sun
Angiogenesis is an essential event in tumor growth and metastasis, and immune system also contributes to the tumor evasion. Emerging evidences have suggested the bidirectional link between angiogenesis and immunosuppression. Myeloid-derived suppressor cell (MDSC) is a kind of immunosuppressive cells and plays an important role in this process. However, the actual regulatory mechanisms of angiogenesis and MDSCs in head and neck squamous cell carcinoma (HNSCC) were unclear. In this study, through analyzing the immunohistochemistry staining of human HNSCC tissue microarray, we found that the microvascular density (MVD) was significantly increased in HNSCC patients...
December 7, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/29178392/slc34a2-regulates-mir-25-gsk3%C3%AE-signaling-pathway-to-affect-tumor-progression-in-gastric-cancer-stem-cell-like-cells
#19
Lanfang Zhang, Xiaohe Guo, Lili Zhang, Fang Yang, Lei Qin, Dezhong Zhang, Yongmei Qin
A novel paradigm in tumor biology suggests that gastric cancer progression is driven by gastric cancer stem cell-like cells (GCSCs), but molecular mechanisms regulating tumorigenic and self-renewal potential of GCSCs are still unclear. Here, we aim to investigate biological function of SLC34A2 in regulating sphere formation and tumorigenicity (both are the hallmark of CSCs) of GCSCs and its underlying mechanisms. Our findings testified that CD44+ cells which were derived from fresh primary gastric cancer samples and cell lines displayed stem cell-like features...
November 27, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/29197120/resveratrol-inhibits-obesity-associated-adipose-tissue-dysfunction-and-tumor-growth-in-a-mouse-model-of-postmenopausal-claudin-low-breast-cancer
#20
Emily L Rossi, Subreen A Khatib, Steven S Doerstling, Laura W Bowers, Melissa Pruski, Nikki A Ford, Randolph D Glickman, Mengmeng Niu, Peiying Yang, Zhengrong Cui, John DiGiovanni, Stephen D Hursting
Adipose tissue dysregulation, a hallmark of obesity, contributes to a chronic state of low-grade inflammation and is associated with increased risk and progression of several breast cancer subtypes, including claudin-low breast tumors. Unfortunately, mechanistic targets for breaking the links between obesity-associated adipose tissue dysfunction, inflammation, and claudin-low breast cancer growth have not been elucidated. Ovariectomized female C57BL/6 mice were randomized (n = 15/group) to receive a control diet, a diet-induced obesity (DIO) diet, or a DIO + resveratrol (0...
November 20, 2017: Molecular Carcinogenesis
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