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https://www.readbyqxmd.com/read/28667779/suberoylanilide-hydroxamic-acid-induces-thioredoxin1-mediated-apoptosis-in-lung-cancer-cells-via-up-regulation-of-mir-129-5p
#1
Bo Ra You, Woo Hyun Park
Histone deacetylase (HDAC) inhibitors, especially suberoylanilide hydroxamic acid (SAHA) induce apoptosis in various cancer cells. Here, we investigated the effect of SAHA on apoptosis in lung cancer cells and addressed the role of reactive oxygen species (ROS), glutathione (GSH), and thioredoxin1 (Trx1) levels in this process. We also identified the miRNAs that down-regulate Trx1 expression at RNA level and thereby influence apoptotic cell death of SAHA increased intracellular ROS levels and promoted apoptotic cell death in cancerous cells but not in non-cancerous normal lung cells...
July 1, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28623912/role-of-epigenetics-microrna-axis-in-drug-resistance-of-multiple-myeloma
#2
REVIEW
Nasrin Rastgoo, Jahangir Abdi, Jian Hou, Hong Chang
Despite administration of novel therapies, multiple myeloma (MM) remains incurable with resistance to drugs leading to relapse in most patients. Thus, it is critical to understand the detailed mechanisms underlying the drug resistance of MM and develop more effective therapeutic strategies. Genetic abnormalities are well known to play a central role in MM pathogenesis and therapy resistance; however, epigenetic aberrations mainly affecting the patterns of DNA methylation/histone modifications of genes (especially tumor suppressors) and miRNAs have also been shown to be involved...
June 17, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28550492/microrna-889-is-downregulated-by-histone-deacetylase-inhibitors-and-confers-resistance-to-natural-killer-cytotoxicity-in-hepatocellular-carcinoma-cells
#3
Haitao Xie, Qiugui Zhang, Hui Zhou, Jun Zhou, Ji Zhang, Yan Jiang, Jinghong Wang, Xianglin Meng, Leping Zeng, Xiaoxin Jiang
Major histocompatibility complex class I chain-related gene B (MICB) is expressed on tumor cells and participates in natural killer (NK) cell-mediated antitumor immune response through engagement with the NKG2D receptor. This study was undertaken to identify novel microRNA (miRNA) regulators of MICB and clarify their functions in NK cell-mediated cytotoxicity to hepatocellular carcinoma (HCC) cells. Bioinformatic analysis and luciferase reporter assay were conducted to search for MICB-targeting miRNAs. Overexpression and knockdown experiments were performed to determine the roles of candidate miRNAs in the susceptibility of HCC cells to NK lysis...
May 26, 2017: Cytotechnology
https://www.readbyqxmd.com/read/28486946/thymic-epithelial-tumors-phenotype-relies-on-mir-145-5p-epigenetic-regulation
#4
Teresa Bellissimo, Federica Ganci, Enzo Gallo, Andrea Sacconi, Claudia Tito, Luciana De Angelis, Claudio Pulito, Silvia Masciarelli, Daniele Diso, Marco Anile, Vincenzo Petrozza, Felice Giangaspero, Edoardo Pescarmona, Francesco Facciolo, Federico Venuta, Mirella Marino, Giovanni Blandino, Francesco Fazi
BACKGROUND: Thymoma and thymic carcinoma are the most frequent subtypes of thymic epithelial tumors (TETs). A relevant advance in TET management could derive from a deeper molecular characterization of these neoplasms. We previously identified a set of microRNA (miRNAs) differentially expressed in TETs and normal thymic tissues and among the most significantly deregulated we described the down-regulation of miR-145-5p in TET. Here we describe the mRNAs diversely regulated in TETs and analyze the correlation between these and the miRNAs previously identified, focusing in particular on miR-145-5p...
May 10, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28440397/hypermethylation-of-mirna-589-promoter-leads-to-upregulation-of-hdac5-which-promotes-malignancy-in-non-small-cell-lung-cancer
#5
Changhong Liu, Desheng Lv, Mo Li, Xuefei Zhang, Ge Sun, Yu Bai, Dongmin Chang
Histone deacetylases (HDACs) are crucial for regulating chromatin activity, which plays a critical role in cell proliferation, differentiation, and apoptosis of various cancers. Therefore, HDAC inhibitors have been applied as effective therapeutic agents for cancer treatment. However, the expression profiles and regulatory mechanisms of histone deacetylases in lung cancer are not well understood. In the present study, aberrant high levels of HDAC5 were observed in non-small cell lung cancer (NSCLC) and further analysis indicated a negative relationship between HDAC5 and a tumor suppressor, miR‑589‑5p, in NSCLC specimens...
April 20, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28216661/mir-194-5p-bclaf1-deregulation-in-aml-tumorigenesis
#6
C Dell'Aversana, C Giorgio, L D'Amato, G Lania, F Matarese, S Saeed, A Di Costanzo, V B Petrizzi, C Ingenito, J H A Martens, I Pallavicini, S Minucci, A Carissimo, H G Stunnenberg, L Altucci
Deregulation of epigenetic mechanisms, including miRNA, contributes to leukaemogenesis and drug resistance by interfering with cancer-specific molecular pathways. Here, we show that the balance between miR-194-5p and its newly discovered target BCL2-associated transcription factor 1 (BCLAF1) regulates differentiation and survival of normal haematopoietic progenitors. In acute myeloid leukaemias (AMLs) this balance is perturbed, locking cells into an immature, potentially 'immortal' state. Enhanced expression of miR-194-5p by treatment with the HDAC inhibitor SAHA or by exogenous miR-194-5p expression re-sensitizes cells to differentiation and apoptosis by inducing BCLAF1 to shuttle between nucleus and cytosol...
February 20, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28176652/mechanisms-for-inhibition-of-colon-cancer-cells-by-sulforaphane-through-epigenetic-modulation-of-microrna-21-and-human-telomerase-reverse-transcriptase-htert-down-regulation
#7
Samantha L Martin, Rishabh Kala, Trygve O Tollefsbol
Epigenetic modulations such as histone modifications are becoming increasingly valued for their ability to modify genes without altering the DNA sequence. Many bioactive compounds have been shown to alter genetic and epigenetic profiles in various forms of 6 cancers. Of the many dietary phytochemicals, sulforaphane (SFN), found in cruciferous vegetables such as kale, cabbage and broccoli sprouts, has been present as one of the most potent (histone deacetylase) HDAC inhibitors to date. Recently, it has been 9 identified that HDAC inhibitors may play a vital role in regulating microRNAs (miRNAs) in many human cancers...
February 5, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28063219/microrna-1-overexpression-blunts-cardiomyocyte-hypertrophy-elicited-by-thyroid-hormone
#8
Gabriela Placoná Diniz, Caroline Antunes Lino, Camila Rodrigues Moreno, Nathalia Senger, Maria Luiza Morais Barreto-Chaves
It is well-known that increased thyroid hormone (TH) levels induce cardiomyocyte growth. MicroRNAs (miRNAs) have been identified as key players in cardiomyocyte hypertrophy, which is associated with increased risk of heart failure. In this study, we evaluated the miR-1 expression in TH-induced cardiac hypertrophy, as well as the potential involvement of miR-1 in cardiomyocyte hypertrophy elicited by TH in vitro. The possible role of type 1 angiotensin II receptor (AT1R) in the effect promoted by TH in miR-1 expression was also evaluated...
January 7, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28031235/htp-nutraceutical-screening-for-histone-deacetylase-inhibitors-and-effects-of-hdacis-on-tumor-suppressing-mirnas-by-trichostatin-a-and-grapeseed-vitis-vinifera-in-hela-cells
#9
Elizabeth A Mazzio, Karam F A Soliman
BACKGROUND/AIM: Aggressive tumor malignancies are a consequence of delayed diagnosis, epigenetic/phenotype changes and chemo-radiation resistance. Histone deacetylases (HDACs) are a major epigenetic regulator of transcriptional repression, which are highly overexpressed in advanced malignancy. While original chemotherapy drugs were modeled after phytochemicals elucidated by botanical screenings, HDAC inhibitors (HDACi) such as apicidin, trichostatin A (TSA) and butyrate were discovered as products of fungus and microbes, in particular, gut microbiota...
January 2, 2017: Cancer Genomics & Proteomics
https://www.readbyqxmd.com/read/27884978/oestrogen-receptor-negativity-in-breast-cancer-a-cause-or-consequence
#10
REVIEW
Vijaya Narasihma Reddy Gajulapalli, Vijaya Lakshmi Malisetty, Suresh Kumar Chitta, Bramanandam Manavathi
Endocrine resistance, which occurs either by de novo or acquired route, is posing a major challenge in treating hormone-dependent breast cancers by endocrine therapies. The loss of oestrogen receptor α (ERα) expression is the vital cause of establishing endocrine resistance in this subtype. Understanding the mechanisms that determine the causes of this phenomenon are therefore essential to reduce the disease efficacy. But how we negate oestrogen receptor (ER) negativity and endocrine resistance in breast cancer is questionable...
December 2016: Bioscience Reports
https://www.readbyqxmd.com/read/27771718/sodium-butyrate-upregulates-mir-203-expression-to-exert-anti-proliferation-effect-on-colorectal-cancer-cells
#11
Ruirui Han, Qianqian Sun, Jianbo Wu, Pengyuan Zheng, Guoqiang Zhao
BACKGROUND: As the end product of the bacterial fermentation of dietary fiber in the colonic lumen, sodium butyrate (NaBt) has been reported to exert antitumor effects on colorectal cancer (CRC). In addition to functioning as a histone deacetylase (HDAC) inhibitor, NaBt also regulates the expression of microRNAs (miRNAs) to inhibit CRC cell proliferation. Yet, the mechanisms involved are not completely understood. Here we investigate whether NaBt regulates miR-203 to inhibit CRC growth and explore the promising target gene of miR-203 in CRC cells...
2016: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/27756747/targeting-btk-through-microrna-in-chronic-lymphocytic-leukemia
#12
Arianna Bottoni, Lara Rizzotto, Tzung-Huei Lai, Chaomei Liu, Lisa L Smith, Rose Mantel, Sean Reiff, Dalia El-Gamal, Karilyn Larkin, Amy J Johnson, Rosa Lapalombella, Amy Lehman, William Plunkett, John C Byrd, James S Blachly, Jennifer A Woyach, Deepa Sampath
Bruton's tyrosine kinase (BTK) is a critical mediator of survival in B-cell neoplasms. Although BTK inhibitors have transformed therapy in chronic lymphocytic leukemia (CLL), patients with high-risk genetics are at risk for relapse and have a poor prognosis. Identification of novel therapeutic strategies for this group of patients is an urgent unmet clinical need, and therapies that target BTK via alternative mechanisms may fill this niche. Herein, we identify a set of microRNAs (miRs) that target BTK in primary CLL cells and show that the histone deacetylase (HDAC) repressor complex is recruited to these miR promoters to silence their expression...
December 29, 2016: Blood
https://www.readbyqxmd.com/read/27706732/changes-in-expression-of-specific-mirnas-and-their-target-genes-in-repair-of-exercise-induced-muscle-injury-in-rats
#13
W Wu
The effects of muscle-specific miRNAs in the repair of exercise-induced muscle injury were investigated by examining the changes in their expression and that of the target genes in rat skeletal muscle. Two-month-old agile male rats were randomly divided into exercise and static control groups, the former subdivided into 0-h, 6-h, 12-h, 1-day, 2-day, 3-day, 1-week, and 2-week groups based on time after exercise. Left gastrocnemii of rats were hematoxylin-eosin stained whereas the right gastrocnemii were used for expression analysis of muscle-specific miRNAs (miR-1 and miR-206) and their target genes, Cx43 and HDAC...
September 16, 2016: Genetics and Molecular Research: GMR
https://www.readbyqxmd.com/read/27502208/novel-saha-analogues-inhibit-hdacs-induce-apoptosis-and-modulate-the-expression-of-micrornas-in-hepatocellular-carcinoma
#14
Chatla Srinivas, V Swathi, C Priyanka, T Anjana Devi, B V Subba Reddy, M Janaki Ramaiah, Utpal Bhadra, Manika Pal Bhadra
In eukaryotes, transcriptional regulation occurs via chromatin remodeling, mainly through post translational modifications of histones that package DNA into structural units. Histone deacetylases (HDACs) are enzymes that play important role in various biological processes by repressing gene expression. Suberoylanilide hydroxamic acid (SAHA) is a known HDAC inhibitor that showed significant anti cancer activity by relieving gene silencing against hematologic and solid tumors. We have designed and synthesized a series of SAHA analogs C1-C4 and performed biological studies to elucidate its anti-cancer effects...
November 2016: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/27448447/microrna-21-drives-severe-steroid-insensitive-experimental-asthma-by-amplifying-phosphoinositide-3-kinase-mediated-suppression-of-histone-deacetylase-2
#15
Richard Y Kim, Jay C Horvat, James W Pinkerton, Malcolm R Starkey, Ama T Essilfie, Jemma R Mayall, Prema M Nair, Nicole G Hansbro, Bernadette Jones, Tatt Jhong Haw, Krishna P Sunkara, Thi Hiep Nguyen, Andrew G Jarnicki, Simon Keely, Joerg Mattes, Ian M Adcock, Paul S Foster, Philip M Hansbro
BACKGROUND: Severe steroid-insensitive asthma is a substantial clinical problem. Effective treatments are urgently required, however, their development is hampered by a lack of understanding of the mechanisms of disease pathogenesis. Steroid-insensitive asthma is associated with respiratory tract infections and noneosinophilic endotypes, including neutrophilic forms of disease. However, steroid-insensitive patients with eosinophil-enriched inflammation have also been described. The mechanisms that underpin infection-induced, severe steroid-insensitive asthma can be elucidated by using mouse models of disease...
February 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/27309669/molecular-dissection-of-valproic-acid-effects-in-acute-myeloid-leukemia-identifies-predictive-networks
#16
RANDOMIZED CONTROLLED TRIAL
Frank G Rücker, Katharina M Lang, Markus Fütterer, Vladimir Komarica, Mathias Schmid, Hartmut Döhner, Richard F Schlenk, Konstanze Döhner, Steen Knudsen, Lars Bullinger
Histone deacetylase inhibitors (HDACIs) like valproic acid (VPA) display activity in leukemia models and induce tumor-selective cytotoxicity against acute myeloid leukemia (AML) blasts. As there are limited data on HDACIs effects, we aimed to dissect VPA effects in vitro using myeloid cell lines with the idea to integrate findings with in vivo data from AML patients treated with VPA additionally to intensive chemotherapy (n = 12). By gene expression profiling we identified an in vitro VPA response signature enriched for genes/pathways known to be implicated in cell cycle arrest, apoptosis, and DNA repair...
July 2, 2016: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/27216188/histone-deacetylase-inhibition-in-prostate-cancer-triggers-mir-320-mediated-suppression-of-the-androgen-receptor
#17
Shinya Sato, Keisuke Katsushima, Keiko Shinjo, Akira Hatanaka, Fumiharu Ohka, Shugo Suzuki, Aya Naiki-Ito, Norihito Soga, Satoru Takahashi, Yutaka Kondo
Targeting androgen receptor (AR) by pharmacologic intervention is one of the effective approaches for treatment of malignant prostate cancers. Histone deacetylase (HDAC) alters the epigenetic status of tumor-associated genes, including those for miRNAs (miRNA), and affects the behavior of cancers. Here, we examined the molecular effects of a HDAC inhibitor, OBP-801, on AR expression and tumor cell growth in prostate cancers. Treatment with OBP-801 efficiently suppressed cell growth of three prostate cancer lines (22Rv1, VCaP, and LNCaP), together with AR downregulation, regardless of their hormone sensitivity...
July 15, 2016: Cancer Research
https://www.readbyqxmd.com/read/27196750/therapeutic-targeting-of-mir-29b-hdac4-epigenetic-loop-in-multiple-myeloma
#18
Nicola Amodio, Maria Angelica Stamato, Anna Maria Gullà, Eugenio Morelli, Enrica Romeo, Lavinia Raimondi, Maria Rita Pitari, Ida Ferrandino, Gabriella Misso, Michele Caraglia, Ida Perrotta, Antonino Neri, Mariateresa Fulciniti, Christian Rolfo, Kenneth C Anderson, Nikhil C Munshi, Pierosandro Tagliaferri, Pierfrancesco Tassone
Epigenetic abnormalities are common in hematologic malignancies, including multiple myeloma, and their effects can be efficiently counteracted by a class of tumor suppressor miRNAs, named epi-miRNAs. Given the oncogenic role of histone deacetylases (HDAC) in multiple myeloma, we investigated whether their activity could be antagonized by miR-29b, a well-established epi-miRNA. We demonstrated here that miR-29b specifically targets HDAC4 and highlighted that both molecules are involved in a functional loop. In fact, silencing of HDAC4 by shRNAs inhibited multiple myeloma cell survival and migration and triggered apoptosis and autophagy, along with the induction of miR-29b expression by promoter hyperacetylation, leading to the downregulation of prosurvival miR-29b targets (SP1, MCL-1)...
June 2016: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/27184529/histone-deacetylase-inhibition-regulates-mir-449a-levels-in-skeletal-muscle-cells
#19
Shagun Poddar, Devesh Kesharwani, Malabika Datta
microRNAs (miRNAs) are small non-coding RNAs that regulate cellular processes by fine-tuning the levels of their target mRNAs. However, the regulatory elements determining cellular miRNA levels are not well studied. Previously, we had described an altered miRNA signature in the skeletal muscle of db/db mice. Here, we sought to explore the role of epigenetic mechanisms in altering these miRNAs. We show that histone deacetylase (HDAC) protein levels and activity are upregulated in the skeletal muscle of diabetic mice...
August 2, 2016: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/27109020/epidrugs-in-the-immunotherapy-of-cutaneous-and-uveal-melanoma
#20
REVIEW
Mario Venza, Maria Visalli, Teresa Catalano, Concetta Beninati, Diana Teti, Isabella Venza
Epigenetic modifications can affect numerous mechanisms used by neoplastic cells to evade immune control. In melanoma epigenetic defects, caused by dysregulations in the expression of genome writers, erasers, or readers, play a significant role in the reduced expression of molecules required for efficient immune recognition as well as antigen presentation and processing. Alterations in gene expression were identified in tumor-associated antigens (TAAs), human leukocyte antigen (HLA) complex, co-stimulatory/accessory molecules, antigen processing machinery (APM), and NKG2D ligands that have shown to be silenced or down-regulated in melanoma...
2017: Anti-cancer Agents in Medicinal Chemistry
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