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transcription initiation

Yue Guo, Renyi Wu, John M Gaspar, Davit Sargsyan, Zheng-Yuan Su, Chengyue Zhang, Linbo Gao, David Cheng, Wenji Li, Chao Wang, Ran Yin, Mingzhu Fang, Michael P Verzi, Ronald P Hart, Ah-Ng Kong
Inflammation is highly associated with colon carcinogenesis. Epigenetic mechanisms could play an important role in the initiation and progression of colon cancer. Curcumin, a dietary phytochemical, shows promising effects in suppressing colitis-associated colon cancer in AOM-DSS mice. However, the potential epigenetic mechanisms of curcumin in colon cancer remain unknown. In this study, the anti-cancer effect of curcumin in suppressing colon cancer in an 18-week AOM-DSS colon cancer mouse model was confirmed...
March 14, 2018: Carcinogenesis
Martin A Bewley, Richard C Budd, Eilise Ryan, Joby Cole, Paul Collini, Jennifer Marshall, Umme Kolsum, Gussie Beech, Richard D Emes, Irina Tcherniaeva, Guy A M Berbers, Sarah R Walmsley, Gavin Donaldson, Jadwiga A Wedzicha, Iain Kilty, William Rumsey, Yolanda Sanchez, Christopher E Brightling, Louise E Donnelly, Peter J Barnes, Dave Singh, Moira K B Whyte, David H Dockrell
RATIONALE: Previous studies have identified defects in bacterial phagocytosis by alveolar macrophages (AM) in patients with chronic obstructive pulmonary disease (COPD) but the mechanisms and clinical consequences remain incompletely defined. OBJECTIVES: To examine the effect of COPD on AM phagocytic responses and identify the mechanisms, clinical consequences and potential for therapeutic manipulation of these defects. METHODS: We isolated alveolar macrophages (AM) and monocyte-derived macrophages (MDM) from a cohort of COPD patients and controls within the MRC COPD-MAP consortium and measured phagocytosis of bacteria in relation to opsonic conditions and clinical features...
March 16, 2018: American Journal of Respiratory and Critical Care Medicine
Aruna Vashishta, Lukasz P Slomnicki, Maciej Pietrzak, Scott C Smith, Murali Kolikonda, Shivani P Naik, Rosanna Parlato, Michal Hetman
Ribosome biogenesis, including the RNA polymerase 1 (Pol1)-mediated transcription of rRNA, is regulated by the pro-epileptogenic mTOR pathway. Therefore, hippocampal Pol1 activity was examined in mouse models of epilepsy including kainic acid- and pilocarpine-induced status epilepticus (SE) as well as a single seizure in response to pentylenetetrazole (PTZ). Elevated 47S pre-rRNA levels were present acutely after induction of SE suggesting activation of Pol1. Conversely, after a single seizure, 47S pre-rRNA was transiently downregulated with increased levels of unprocessed 18S rRNA precursors in the cornu Ammonis (CA) region...
March 15, 2018: Molecular Neurobiology
Ewa Heyduk, Tomasz Heyduk
Promoter escape involves breaking of the favourable contacts between RNA polymerase (RNAP) and the promoter to allow transition to an elongation complex. The sequence of DNA template that is transcribed during promoter escape (ITS; Initially Transcribed Sequence) can affect promoter escape by mechanisms that are not yet fully understood. We employed a highly parallel strategy utilizing Next Generation Sequencing (NGS) to collect data on escape properties of thousands of ITS variants. We show that ITS controls promoter escape through a combination of position-dependent effects (most prominently, sequence-directed RNAP pausing), and position-independent effects derived from sequence encoded physical properties of the template (for example, RNA/DNA duplex stability)...
March 13, 2018: Nucleic Acids Research
Haiyan Gao, Mei Yang, Xiaolan Zhang
The present study aimed to investigate potential recurrence-risk biomarkers based on significant pathways for Luminal A breast cancer through gene expression profile analysis. Initially, the gene expression profiles of Luminal A breast cancer patients were downloaded from The Cancer Genome Atlas database. The differentially expressed genes (DEGs) were identified using a Limma package and the hierarchical clustering analysis was conducted for the DEGs. In addition, the functional pathways were screened using Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses and rank ratio calculation...
April 2018: Oncology Letters
Lorenza Tulli, Francesca Cattaneo, Juliette Vinot, Cosima T Baldari, Ugo D'Oro
Toll-like receptors (TLRs) play a key role in the activation of innate immune cells, in which their engagement leads to production of cytokines and co-stimulatory molecules. TLRs signaling requires recruitment of toll/IL-1R (TIR) domain-containing adaptors, such as MyD88 and/or TRIF, and leads to activation of several transcription factors, such as NF-κB, the AP1 complex, and various members of the interferon regulatory factor (IRF) family, which in turn results in triggering of several cellular functions associated with these receptors...
2018: Frontiers in Immunology
Elizabeth C Curran, Hui Wang, Thomas R Hinds, Ning Zheng, Edith H Wang
The general transcription factor IID (TFIID) is the first component of the preinitiation complex (PIC) to bind the core promoter of RNA polymerase II transcribed genes. Despite its critical role in protein-encoded gene expression, how TFIID engages promoter DNA remains elusive. We have previously revealed a winged-helix DNA-binding domain in the N-terminal region of the largest TFIID subunit, TAF1. Here, we report the identification of a second DNA-binding module in the C-terminal half of human TAF1, which is encoded by a previously uncharacterized conserved zinc knuckle domain...
March 15, 2018: Scientific Reports
Stephen Safe, James L Abbruzzese, Maen Abdelrahim, Erik Hedrick
Specificity protein (Sp) transcription factors (TFs) such as Sp1 are critical for early development but their expression decreases with age and there is evidence that transformation of normal cells to cancer cells is associated with upregulation of Sp1, Sp3 and Sp4 which are highly expressed in cancer cells and tumors. Sp1 is a negative prognostic factor for pancreatic, colon, glioma, gastric, breast, prostate, and lung cancer patients. Functional studies also demonstrate that Sp TFs regulate genes responsible for cancer cell growth, survival, migration/invasion, inflammation and drug resistance, and Sp1, Sp3 and Sp4 are also non-oncogene addiction (NOA) genes and important drug targets...
March 15, 2018: Cancer Prevention Research
Hetal Patel, Manikandan Periyasamy, Georgina P Sava, Alexander Bondke, Brian W Slafer, Sebastian H B Kroll, Marion Barbazanges, Richard Starkey, Silvia Ottaviani, Alison Harrod, Eric O Aboagye, Laki Buluwela, Matthew J Fuchter, Anthony G M Barrett, Charles Coombes, Simak Ali
Recent reports indicate that some cancer types are especially sensitive to transcription inhibition, suggesting that targeting the transcriptional machinery provides new approaches to cancer treatment. Cyclin-dependent kinase (CDK)7 is necessary for transcription, and acts by phosphorylating the C-terminal domain (CTD) of RNA polymerase II (PolII) to enable transcription initiation. CDK7 additionally regulates the activities of a number of transcription factors, including Estrogen receptor-α (ER). Here we describe a new, orally bioavailable CDK7 inhibitor, ICEC0942...
March 15, 2018: Molecular Cancer Therapeutics
Maioli E, Daveri E, Maellaro E, Ietta F, Cresti L, Valacchi G
In the past few years, we focused the interest on rottlerin, an old/new natural substance that, over the time, has revealed a number of cellular and molecular targets, all potentially implicated in the fight against cancer. Past and recent literature well demonstrated that rottlerin is an inhibitor of enzymes, transcription factors and signaling molecules that control cancer cell life and death. Although the rottlerin anticancer activity has been mainly ascribed to apoptosis and/or autophagy induction, recent findings unveiled the existence of additional mechanisms of toxicity...
March 12, 2018: Archives of Biochemistry and Biophysics
Sajal Kole, Ranjeeta Kumari, Deepika Anand, Saurav Kumar, Rupam Sharma, Gayatri Tripathi, M Makesh, K V Rajendran, Megha Kadam Bedekar
DNA-based immunization has proven to be an effective prophylactic measure to control aquatic animal diseases. In order to improve the efficiency of vaccine against fish pathogen, novel delivery mechanism needs to be adopted. In the present study we nanoconjugated the previously constructed DNA vaccine (pGPD + IFN) with chitosan nanoparticles (CNPs) by complex coacervation process. After construction of the vaccine, an in vivo vaccination trial was conducted in which 2 groups of rohu (L. rohita) fingerlings were vaccinated with CNPs-pGPD + IFN, one group by oral route (incorporated in feed for 14 days) and the other by immersion route (primary and booster immunised), whereas, a third group was intramuscularly (I/M) injected (initial and booster immunised) with naked pGPD + IFN and subsequently challenged with E...
March 12, 2018: Vaccine
Hongbei Xu, Wenyi Qin, Xiao Hu, Song Mu, Jun Zhu, Wenhao Lu, Yong Luo
BACKGROUND: Ischemic stroke-induced neuroinflammation is mainly mediated by microglial cells. The nuclear factor kappa B (NF-κB) pathway is the key transcriptional pathway that initiates inflammatory responses following cerebral ischemia. OTULIN, a critical negative regulator of the NF-κΒ signaling pathway, exerts robust effects on peripheral immune cell-mediated inflammation and is regarded as an essential mediator for repressing inflammation in vivo. The effect of OTULIN on inflammatory responses in the central nervous system (CNS) was previously unstudied...
March 15, 2018: Journal of Neuroinflammation
Jin Ah Cha, Hyo-Sook Song, Beomku Kang, Moon Nyeo Park, Kyoung Sun Park, Sung-Hoon Kim, Bum-Sang Shim, Bonglee Kim
Though Cnidium officinale Makino (COM) was known to have anti-angiogenic, anti-oxidant, neuroprotective, and anti-cancer effects, the underlying anticancer mechanism of COM using endoplasmic reticulum (ER) stress and miRNA remained unclear until now. Thus, in the current study, the inhibitory mechanism of COM in lymphoma and multiple myeloma (MM) cells was elucidated. COM exerted cytotoxicity in U937 and U266 but not Raw264.7 cells. COM treatment increased the expression of ER stress-related proteins such as p-protein kinase RNA-like endoplasmic reticulum kinase (p-PERK), p-eukaryotic initiation factor (p-eIF2α), and activating transcription factor 4 (ATF4) and C/EBP homologous protein (CHOP)...
March 15, 2018: International Journal of Molecular Sciences
Muthu K Shanmugam, Frank Arfuso, Surendar Arumugam, Arunachalam Chinnathambi, Bian Jinsong, Sudha Warrier, Ling Zhi Wang, Alan Prem Kumar, Kwang Seok Ahn, Gautam Sethi, Manikandan Lakshmanan
Oncogenesis is a multistep process mediated by a variety of factors including epigenetic modifications. Global epigenetic post-translational modifications have been detected in almost all cancers types. Epigenetic changes appear briefly and do not involve permanent changes to the primary DNA sequence. These epigenetic modifications occur in key oncogenes, tumor suppressor genes, and transcription factors, leading to cancer initiation and progression. The most commonly observed epigenetic changes include DNA methylation, histone lysine methylation and demethylation, histone lysine acetylation and deacetylation...
February 16, 2018: Oncotarget
Deyuan Zhu, Wenxi Gao, Zhongmin Zhang
In the present study, the aim was to investigate the role of microRNA-1180 (miR-1180) in the growth and apoptosis of prostate cancer, as well as to identify its direct targets. Initially, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was performed to examine the expression of miR-1180 in the prostate cancer tissues and adjacent normal prostate tissues of 30 patients, as well as in DU145 and RWPE-1 cells. Next, DU145 cells were transfected with miR-1180 mimics, and the expression levels of associated proteins were determined by western blot assay...
April 2018: Oncology Letters
Sebastian Buschauer, Andreas Koch, Philipp Wiggermann, Martina Müller, Claus Hellerbrand
Transarterial chemoembolization (TACE) is an established therapeutic approach for the treatment of hepatocellular carcinoma (HCC). Although patients who undergo TACE may have prolonged survival, there are indications that the malignancy of residual HCC tissue can increase subsequent to the procedure. Although hypoxia, which occurs during TACE due to ischemia, is known to contribute to angiogenesis, little is known with regard to the undesirable effects of chemotherapeutic agents on residual HCC cells. Doxorubicin is one of the most commonly used drugs in TACE...
April 2018: Oncology Letters
Kun Xia, Panpan Zhang, Jian Hu, Huan Hou, Mingdi Xiong, Junping Xiong, Nianlong Yan
Hepatocellular carcinoma is the sixth most prevalent malignant tumor and the third most common cause of cancer-associated mortality. Statins have been investigated for carcinoma prevention and treatment. In addition, receptor-interacting protein 140 (RIP140) has been observed to inhibit the Wnt/β-catenin signaling pathway and cell growth. The present study aimed to investigate whether simvastatin (SV) is able to induce SMCC-7721 cell apoptosis through the Wnt/β-catenin signaling pathway. Initially, a cell model of RIP140 overexpression was established, and then cells were treated with SV...
April 2018: Oncology Letters
Joy Ogbechi, Belinda S Hall, Thomas Sbarrato, Jack Taunton, Anne E Willis, Ronald C Wek, Rachel E Simmonds
Mycolactone is the exotoxin virulence factor of Mycobacterium ulcerans that causes the neglected tropical disease Buruli ulcer. We recently showed it to be a broad spectrum inhibitor of Sec61-dependent co-translational translocation of proteins into the endoplasmic reticulum (ER). An outstanding question is the molecular pathway linking this to its known cytotoxicity. We have now used translational profiling to better understand the reprogramming that occurs in cells exposed to mycolactone. Gene ontology identified enrichment in genes involved in cellular response to stress, and apoptosis signalling among those showing enhanced translation...
March 14, 2018: Cell Death & Disease
Laurène Bastet, Pierre Turcotte, Joseph T Wade, Daniel A Lafontaine
Riboswitches are RNA regulators that control gene expression by modulating their structure in response to metabolite binding. The study of mechanisms by which riboswitches modulate gene expression is crucial to understand how riboswitches are involved in maintaining cellular homeostasis. Previous reports indicate that riboswitches can control gene expression at the level of translation, transcription or mRNA decay. However, there are very few described examples where riboswitches regulate multiple steps in gene expression...
March 14, 2018: RNA Biology
Elizabeth Delve, Justin Parreno, Vivian Co, Po-Han Wu, Jasmine Chong, Matteo Di Scipio, Rita A Kandel
Osteoarthritis (OA) is a degenerative disease that initially manifests as loss of the superficial zone (SZ) of articular cartilage. SZ chondrocytes (SZC) differ in morphology from other chondrocytes as they are elongated and oriented parallel to the tissue surface. Proteoglycan 4 (PRG4) and tenascin C (TNC) are molecules expressed by SZC, which have been shown to be chondroprotective. Identification of the signalling pathway(s) regulating expression of SZ molecules may lead to a therapeutic target that can be used to delay or prevent the onset of OA...
March 14, 2018: Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society
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