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https://www.readbyqxmd.com/read/28208156/oncogenic-role-of-pdk4-in-human-colon-cancer-cells
#1
D Leclerc, D N T Pham, N Lévesque, M Truongcao, W D Foulkes, C Sapienza, R Rozen
BACKGROUND: Cancer cells maintain high rates of glycolysis. Pyruvate dehydrogenase kinases (PDK) contribute to this phenomenon, which favours apoptosis resistance and cellular transformation. We previously reported upregulation of PDK4 in normal mucosa of colorectal cancer (CRC) patients compared with controls and in preneoplastic intestine of our mouse model. Decreased methylation of four consecutive PDK4 CpGs was observed in normal mucosa of patients. Although other members of the PDK family have been investigated for transformation potential, PDK4 has not been extensively studied...
February 16, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28202522/histone-acetyltransferase-activity-of-mof-is-required-for-mll-af9-leukemogenesis
#2
Daria G Valerio, Haiming Xu, Chun-Wei Chen, Takayuki Hoshii, Meghan E Eisold, Christopher Delaney, Monica Cusan, Aniruddha J Deshpande, Chun-Hao Huang, Amaia Lujambio, Y George G Zheng, Johannes Zuber, Tej K Pandita, Scott W Lowe, Scott A Armstrong
Chromatin-based mechanisms offer therapeutic targets in acute myeloid leukemia (AML) that are of great current interest. In this study, we conducted an RNAi-based screen to identify druggable chromatin regulator-based targets in leukemias marked by oncogenic rearrangements of the MLL gene. In this manner, we discovered the H4K16 histone acetyltransferase (HAT) MOF to be a potent suppressor of leukemia cell growth. Conditional deletion of Mof in a mouse model of MLL-AF9-driven leukemogenesis reduced tumor burden and prolonged host survival...
February 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28199302/untimely-expression-of-gametogenic-genes-in-vegetative-cells-causes-uniparental-disomy
#3
H Diego Folco, Venkata R Chalamcharla, Tomoyasu Sugiyama, Gobi Thillainadesan, Martin Zofall, Vanivilasini Balachandran, Jothy Dhakshnamoorthy, Takeshi Mizuguchi, Shiv I S Grewal
Uniparental disomy (UPD), in which an individual contains a pair of homologous chromosomes originating from only one parent, is a frequent phenomenon that is linked to congenital disorders and various cancers. UPD is thought to result mostly from pre- or post-zygotic chromosome missegregation. However, the factors that drive UPD remain unknown. Here we use the fission yeast Schizosaccharomyces pombe as a model to investigate UPD, and show that defects in the RNA interference (RNAi) machinery or in the YTH domain-containing RNA elimination factor Mmi1 cause high levels of UPD in vegetative diploid cells...
February 15, 2017: Nature
https://www.readbyqxmd.com/read/28197633/pim1-knockdown-inhibits-cell-proliferation-and-invasion-of-mesothelioma-cells
#4
Amany Sayed Mawas, Vishwa Jeet Amatya, Rui Suzuki, Kei Kushitani, Mouchira M Mohi El-Din, Yukio Takeshima
Malignant mesothelioma is a major asbestos-related cancer with prolonged time lapse from the first exposure of asbestos to the development of mesothelioma. Most of mesothelioma patients show very poor prognosis, thus, an urgent improvement of its treatment is required by development of novel therapeutic strategies. RNA interference (RNAi) is a powerful tool in post-genomic research and cancer therapy through inhibition of gene expression. In the present study, we analyzed the function of PIM1 on mesothelioma cell lines with its knockdown by siRNA transfection...
March 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28197629/rab27a-rab27b-and-vps36-are-downregulated-in-advanced-prostate-cancer-and-show-functional-relevance-in-prostate-cancer-cells
#5
Thomas Stefan Worst, Yannic Meyer, Maria Gottschalt, Cleo-Aron Weis, Jost von Hardenberg, Christine Frank, Annette Steidler, Maurice Stephan Michel, Philipp Erben
Paracrine and long-range signaling via extracellular vesicles, such as exosomes and microvesicles, is deemed crucial for tumorigenesis, invasion and spread of solid tumors. The ESCRT machinery (endosomal sorting complexes required for transport) and Rab-proteins act as key players in vesicular trafficking and secretion. Yet, their role in prostate cancer (PCa) is unknown. Therefore, this study aimed to elucidate the relevance of these components in PCa. In silico reanalysis of genes with known involvement in vesicular trafficking and secretion in an existing microarray dataset revealed low expression of RAB27A, RAB27B and VPS36 to be predictive for reduced BCR-free survival in patients with localized PCa (p=0...
March 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28197418/expression-of-cadherin-17-promotes-metastasis-in-a-highly-bone-marrow-metastatic-murine-breast-cancer-model
#6
Tomoko Okada, Atsushi Kurabayashi, Nobuyoshi Akimitsu, Mutsuo Furihata
We previously established 4T1E/M3 highly bone marrow metastatic mouse breast cancer cells through in vivo selection of 4T1 cells. But while the incidence of bone marrow metastasis of 4T1E/M3 cells was high (~80%) when injected intravenously to mice, it was rather low (~20%) when injected subcutaneously. Therefore, using 4T1E/M3 cells, we carried out further in vitro and in vivo selection steps to establish FP10SC2 cells, which show a very high incidence of metastasis to lungs (100%) and spines (85%) after subcutaneous injection into mice...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28194035/recurrently-deregulated-lncrnas-in-hepatocellular-carcinoma
#7
Yang Yang, Lei Chen, Jin Gu, Hanshuo Zhang, Jiapei Yuan, Qiuyu Lian, Guishuai Lv, Siqi Wang, Yang Wu, Yu-Cheng T Yang, Dongfang Wang, Yang Liu, Jing Tang, Guijuan Luo, Yang Li, Long Hu, Xinbao Sun, Dong Wang, Mingzhou Guo, Qiaoran Xi, Jianzhong Xi, Hongyang Wang, Michael Q Zhang, Zhi John Lu
Hepatocellular carcinoma (HCC) cells often invade the portal venous system and subsequently develop into portal vein tumour thrombosis (PVTT). Long noncoding RNAs (lncRNAs) have been associated with HCC, but a comprehensive analysis of their specific association with HCC metastasis has not been conducted. Here, by analysing 60 clinical samples' RNA-seq data from 20 HCC patients, we have identified and characterized 8,603 candidate lncRNAs. The expression patterns of 917 recurrently deregulated lncRNAs are correlated with clinical data in a TCGA cohort and published liver cancer data...
February 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/28179588/tp53-based-interaction-analysis-identifies-cis-eqtl-variants-for-tp53bp2-fbxo28-and-fam53a-that-associate-with-survival-and-treatment-outcome-in-breast-cancer
#8
Rainer Fagerholm, Sofia Khan, Marjanka K Schmidt, Montserrat García-Closas, Päivi Heikkilä, Jani Saarela, Jonathan Beesley, Maral Jamshidi, Kristiina Aittomäki, Jianjun Liu, H Raza Ali, Irene L Andrulis, Matthias W Beckmann, Sabine Behrens, Fiona M Blows, Hermann Brenner, Jenny Chang-Claude, Fergus J Couch, Kamila Czene, Peter A Fasching, Jonine Figueroa, Giuseppe Floris, Gord Glendon, Qi Guo, Per Hall, Emily Hallberg, Ute Hamann, Bernd Holleczek, Maartje J Hooning, John L Hopper, Agnes Jager, Maria Kabisch, Renske Keeman, Veli-Matti Kosma, Diether Lambrechts, Annika Lindblom, Arto Mannermaa, Sara Margolin, Elena Provenzano, Mitul Shah, Melissa C Southey, Joe Dennis, Michael Lush, Kyriaki Michailidou, Qin Wang, Manjeet K Bolla, Alison M Dunning, Douglas F Easton, Paul D P Pharoah, Georgia Chenevix-Trench, Carl Blomqvist, Heli Nevanlinna
TP53 overexpression is indicative of somatic TP53 mutations and associates with aggressive tumors and poor prognosis in breast cancer. We utilized a two-stage SNP association study to detect variants associated with breast cancer survival in a TP53-dependent manner. Initially, a genome-wide study (n = 575 cases) was conducted to discover candidate SNPs for genotyping and validation in the Breast Cancer Association Consortium (BCAC). The SNPs were then tested for interaction with tumor TP53 status (n = 4,610) and anthracycline treatment (n = 17,828)...
February 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28178195/overexpression-of-skp2-inhibits-the-radiation-induced-bystander-effects-of-esophageal-carcinoma
#9
Xiao-Chun Wang, Tie-Jun Zhang, Zi-Jian Guo, Chang-Yan Xiao, Xiao-Wen Ding, Fang Fang, Wen-Tao Sheng, Xu Shu, Jue Li
BACKGROUND: To investigate the effects of S-phase kinase protein 2 (SKP2) expression on the radiation induced bystander effect (RIBE) in esophageal cancer (EC) cells. MATERIALS AND METHODS: Western blot was used to detect the levels of SKP2, Rad51, and Ku70 in EC cells. Positive transfection, RNAi, micronucleus (MN), and γ-H2AX focus formation assay were used to investigate the effects of SKP2 on RIBE induced by irradiated cells. RESULTS: We found a significant negative correlation between SKP2 expression and MN frequency (p < 0...
February 6, 2017: International Journal of Environmental Research and Public Health
https://www.readbyqxmd.com/read/28170265/immunoprotein-mediated-sirna-delivery
#10
Nicole Bäumer, Wolfgang E Berdel, Sebastian Bäumer
RNA interference strategies offer an alternative to small molecular drug targeting. Small interfering RNA (siRNA) constitutes a class of molecules that allows the effective and specific inhibition of the biosynthesis of any protein. Indeed, siRNA have emerged as a major tool in molecular biology techniques and an important approach to identify suitable therapy targets in cancer. However, siRNA therapy approaches in vivo are scarce. Two major problems hinder siRNA as a therapeutic tool: (1) delivery through the bloodstream leads to degradation or rapid renal clearance (stabilization) and (2) specific uptake by the desired cell type (specificity)...
February 15, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28170160/generation-of-an-inducible-mouse-model-to-reversibly-silence-stat3
#11
Mariah G Alorro, Thomas P Pierce, Moritz F Eissmann, Christine Dijkstra, Ross A Dickins, Matthias Ernst, Michael Buchert, Frederick Masson
Signal transducer and activator of transcription 3 (Stat3) is a transcription factor that has many essential roles during inflammation, development and cancer. Stat3 is therefore an attractive therapeutic target in many diseases. While current Stat3 knockout mouse models led to a better understanding of the role of Stat3, the irreversible nature of Stat3 ablation does not model the effects of transient Stat3 therapeutic inhibition, and does not inform on potential dosage effects of Stat3. Using RNAi technology, we have generated a new mouse model allowing the inducible and reversible silencing of Stat3 in vivo, which mirrors the effects of specific Stat3 therapeutic interference...
February 7, 2017: Genesis: the Journal of Genetics and Development
https://www.readbyqxmd.com/read/28166401/maximizing-synergistic-activity-when-combining-rnai-and-platinum-based-anticancer-agents
#12
Haihua Xiao, Ruogu Qi, Ting Li, Samuel G Awuah, Yaorong Zheng, Wei Wei, Xiang Kang, Haiqin Song, Yongheng Wang, Yingjie Yu, Molly A Bird, Xiabin Jing, Michael B Yaffe, Michael J Birrer, P Peter Ghoroghchian
RNAi approaches have been widely combined with platinum-based anticancer agents to elucidate cellular responses and to target gene products that mediate acquired resistance. Recent work has demonstrated that platination of siRNA prior to transfection may negatively influence RNAi efficiency based on the position and sequence of its guanosine nucleosides. Here, we used detailed spectroscopic characterization to demonstrate rapid formation of Pt-guanosine adducts within 30 min after coincubation of oxaliplatin [OxaPt(II)] or cisplatin [CisPt(II)] with either guanosine monophosphate or B-cell lymphoma 2 (BCL-2) siRNA...
February 16, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28148541/silencing-the-roadblocks-to-effective-tnbc-treatments-by-sirna-nanoparticles
#13
Jenny G Parvani, Mark W Jackson
Over the past decade, RNA interference (RNAi) has been ubiquitously utilized to study biological function in vitro, however limitations were associated with its utility in vivo. More recently, small interfering RNA (siRNA) nanoparticles with improved biocompatibility have gained prevalence as a potential therapeutic option for the treatment of various diseases. The adaptability of siRNA nanoparticles enables the delivery of virtually any siRNA, which is especially advantageous for therapeutic applications in heterogeneous diseases that lack unifying molecular features, such as triple negative breast cancer (TNBC)...
February 1, 2017: Endocrine-related Cancer
https://www.readbyqxmd.com/read/28131992/the-mll1-h3k4me3-axis-mediated-pd-l1-expression-and-pancreatic-cancer-immune-evasion
#14
Chunwan Lu, Amy V Paschall, Huidong Shi, Natasha Savage, Jennifer L Waller, Maria E Sabbatini, Nicholas H Oberlies, Cedric Pearce, Kebin Liu
BACKGROUND: Pancreatic cancer is one of the cancers where anti-PD-L1/PD-1 immunotherapy has been unsuccessful. What confers pancreatic cancer resistance to checkpoint immunotherapy is unknown. The aim of this study is to elucidate the underlying mechanism of PD-L1 expression regulation in the context of pancreatic cancer immune evasion. METHODS: Pancreatic cancer mouse models and human specimens were used to determine PD-L1 and PD-1 expression and cancer immune evasion...
January 2017: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/28125794/development-of-novel-small-hairpin-rnas-that-do-not-require-processing-by-dicer-or-ago2
#15
Shin-Ichiro Ohno, Karen Itano, Yuichirou Harada, Koutaro Asada, Keiki Oikawa, Mikie Kashiwazako, Hikaru Okuyama, Katsuyoshi Kumagai, Masakatsu Takanashi, Katsuko Sudo, Norihiko Ikeda, Masahiko Kuroda
The innate cytokine response to nucleic acid is the most challenging problem confronting the practical use of nucleic acid medicine. The degree of stimulation of the innate cytokine response strongly depends on the length of the nucleic acid. In this study, we developed a 30-nucleotide single-strand RNA, termed "guide hairpin RNA (ghRNA, ghR)", that has a physiological function similar to that of miRNA and siRNA. The ghR caused no innate cytokine response either in vitro or in vivo. In addition, its structure does not contain a passenger strand seed sequence, reducing the unwanted gene repression relative to existing short RNA reagents...
July 2016: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28123172/knockdown-of-tctn1-strongly-decreases-growth-of-human-colon-cancer-cells
#16
Xiaoyu Dai, Mingjun Dong, Hua Yu, Yangyang Xie, Yongming Yu, Yisheng Cao, Zhenfang Kong, Baofeng Zhou, Yidong Xu, Tong Yang, Keqiang Li
BACKGROUND Tectonic family member 1 (TCTN1), a member of the tectonic family, is involved in several developmental processes and is aberrantly expressed in multiple solid tumors. However, the expression and regulation of TCTN1 in human colorectal cancer (CRC) is still not clear. MATERIAL AND METHODS The expression of TCTN1 mRNA was first explored by using Oncomine microarray datasets. TCTN1 expression was silenced in human CRC cell lines HCT116 and SW1116 via RNA interference (RNAi). Furthermore, we investigated the effect of TCTN1 depletion on CRC cell growth by MTT, colony formation, and flow cytometry in vitro...
January 26, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28119429/novel-assay-to-detect-rna-polymerase-i-activity-in-vivo
#17
Gunes Guner, Paul Sirajuddin, Qizhi Zheng, Baoyan Bai, Alexandra Brodie, Hester Liu, Taija Af Hallstrom, Ibrahim Kulac, Marikki Laiho, Angelo M De Marzo
: This report develops an analytically validated chromogenic in situ hybridization (CISH) assay using branched DNA signal amplification (RNAscope) for detecting the expression of the 5' external transcribed spacer (ETS) of the 45S ribosomal (r) RNA precursor in formalin fixed and paraffin embedded (FFPE) human tissues. 5'ETS/45S CISH was performed on standard clinical specimens and tissue microarrays (TMAs) from untreated prostate carcinomas, high-grade prostatic intraepithelial neoplasia (PIN) and matched benign prostatic tissues...
January 23, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28113326/nanoparticles-for-sirna-based-gene-silencing-in-tumor-therapy
#18
Anish Babu, Ranganayaki Muralidharan, Narsireddy Amreddy, Meghna Mehta, Anupama Munshi, Rajagopal Ramesh
Gene silencing through RNA interference (RNAi) has emerged as a potential strategy in manipulating cancer causing genes by complementary base-pairing mechanism. Small interfering RNA (siRNA) is an important RNAi tool that has found significant application in cancer therapy. However due to lack of stability, poor cellular uptake and high probability of loss-of-function due to degradation, siRNA therapeutic strategies seek safe and efficient delivery vehicles for in vivo applications. The current review discusses various 2 nanoparticle systems currently used for siRNA delivery for cancer therapy, with emphasis on liposome based gene delivery systems...
December 15, 2016: IEEE Transactions on Nanobioscience
https://www.readbyqxmd.com/read/28106737/a-novel-combination-rnai-toward-warburg-effect-by-replacement-with-mir-145-and-silencing-of-ptbp1-induces-apoptotic-cell-death-in-bladder-cancer-cells
#19
Tomoaki Takai, Yuki Yoshikawa, Teruo Inamoto, Koichiro Minami, Kohei Taniguchi, Nobuhiko Sugito, Yuki Kuranaga, Haruka Shinohara, Minami Kumazaki, Takuya Tsujino, Kiyoshi Takahara, Yuko Ito, Yukihiro Akao, Haruhito Azuma
Bladder cancer is one of the most difficult malignancies to control. We explored the use of a novel RNA-interference method for a driver oncogene regulating cancer specific energy metabolism by the combination treatment with a small interfering RNA (siRNA) and a microRNA. After transfection of T24 and 253JB-V cells with miR-145 and/or siR-PTBP1, we examined the effects of cell growth and gene expression by performing the trypan blue dye exclusion test, Western blot, Hoechst 33342 staining, reverse transcription polymerase chain reaction (RT-PCR), and electron microscopy...
January 17, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28105147/fgfr3-silencing-by-sirna-inhibits-invasion-of-a549-cells
#20
Yuhua Li, Xiguang Liu, Hongjun Zhang, Tao Jiang, Wenjing Xiao, Shufen Zhao, Xiaoyun Yu, Fanjie Han
The present study identified that fibroblast growth factor receptor 3 (FGFR3) was significantly upregulated in bone metastasis of lung adenocarcinoma. RNA interference (RNAi) is a powerful approach for treating a wide range of human diseases, including cancer, through downregulating the expression of selected genes. In the present study, the invasiveness of A549 cells cultured in vitro was altered by small interfering (si)RNA targeting FGFR3, and the regulatory effect of silencing FGFR3 on the expression levels of E-cadherin and matrix metalloproteinase (MMP)9 was investigated...
December 2016: Oncology Letters
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