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https://www.readbyqxmd.com/read/27884978/estrogen-receptor-negativity-in-breast-cancer-a-cause-or-consequence
#1
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 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 estrogen receptor (ER) negativity and endocrine resistance in breast cancer is questionable, to answer that two important approaches are considered: 1) Understanding the cellular origin of heterogeneity and ER negativity in breast cancers, and 2) characterization of molecular regulators of endocrine resistance...
November 24, 2016: Bioscience Reports
https://www.readbyqxmd.com/read/27771718/sodium-butyrate-upregulates-mir-203-expression-to-exert-anti-proliferation-effect-on-colorectal-cancer-cells
#2
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...
October 24, 2016: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/27756747/targeting-btk-through-microrna-in-chronic-lymphocytic-leukemia
#3
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
BTK is a critical mediator of survival in B cell neoplasms. While BTK inhibitors have transformed therapy in CLL, high genetic risk patients 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 miRNAs that target BTK in primary CLL cells and show that the HDAC repressor complex is recruited to these miRNA promoters to silence their expression...
October 17, 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
#4
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
#5
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
#6
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...
June 10, 2016: 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
#7
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
#8
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
#9
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
#10
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
#11
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 been shown to be silenced or down-regulated in melanoma...
April 25, 2016: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/27072566/regulation-of-runx2-by-histone-deacetylases-in-bone
#12
Mohanakrishnan Vishal, Ramachandran Ajeetha, Rajendran Keerthana, Nagarajan Selvamurugan
Osteogenesis involves a cascade of processes wherein mesenchymal stem cells differentiate towards osteoblasts, strictly controlled by a number of regulatory factors. Runx2 protein is a key transcription factor which serves as a master regulator for osteogenesis by activating the promoters of various osteoblastic genes. Runx2 is regulated by several cofactors, including the histone deacetylase enzymes known as HDACs. HDACs are a family of proteins that regulate gene expression and/or activity through the mechanism of deacetylation and they can be divided into four classes, namely classes I, II, III and IV HDACs based on their sequence identity and nuclear or cytoplasmic localization...
2016: Current Protein & Peptide Science
https://www.readbyqxmd.com/read/27022108/therapeutic-targeting-of-mir-29b-hdac4-epigenetic-loop-in-multiple-myeloma
#13
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 (MM), and their effects can be efficiently counteracted by a class of tumor suppressor microRNAs, named epi-miRNAs. Given the oncogenic role of histone deacetylases (HDACs) in MM, we investigated if their activity could be antagonized by miR-29b, a well-established epi-miRNA. We demonstrated here that miR-29b specifically targets HDAC4 and we highlighted that both molecules are involved in a functional loop. In fact, silencing of HDAC4 by shRNAs inhibited MM cell survival and migration and triggered apoptosis and autophagy, along with induction of miR-29b expression by promoter hyperacetylation, leading to downregulation of pro-survival miR-29b targets (SP1, MCL-1)...
March 28, 2016: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/26921097/social-isolation-mediated-anxiety-like-behavior-is-associated-with-enhanced-expression-and-regulation-of-bdnf-in-the-female-mouse-brain
#14
Anita Kumari, Padmanabh Singh, Meghraj Singh Baghel, M K Thakur
Adverse early life experience is prominent risk factors for numerous psychiatric illnesses, including mood and anxiety disorders. It imposes serious long-term costs on the individual as well as health and social systems. Hence, developing therapies that prevent the long-term consequences of early life stress is of utmost importance, and necessitates a better understanding of the mechanisms by which early life stress triggers long-lasting alterations in gene expression and behavior. Post-weaning isolation rearing of rodents models the behavioral consequences of adverse early life experiences in humans and it is reported to cause anxiety like behavior which is more common in case of females...
May 1, 2016: Physiology & Behavior
https://www.readbyqxmd.com/read/26915294/histone-deacetylase-inhibition-reveals-a-tumor-suppressive-function-of-myc-regulated-mirna-in-breast-and-lung-carcinoma
#15
C M Adams, C M Eischen
Histone deacetylase (HDAC) inhibition leads to dynamic changes in the epigenetic landscape that is postulated to alter the expression of critical mediators of cellular proliferation and death. While current HDAC inhibitors have shown to be efficacious in the treatment of specific hematologic malignancies, their therapeutic utility in epithelial-based cancers warrants further evaluation. Moreover, the mechanisms of HDAC inhibition-induced cancer cell death are not completely understood. Therefore, elucidation of the underlying pathways engaged by HDAC inhibition may enable the development of more effective therapeutic strategies...
August 2016: Cell Death and Differentiation
https://www.readbyqxmd.com/read/26849145/impaired-expression-of-dicer-and-some-micrornas-in-hbz-expressing-cells-from-acute-adult-t-cell-leukemia-patients
#16
Hélène Gazon, Gildas Belrose, Marie Terol, Jean-Come Meniane, Jean-Michel Mesnard, Raymond Césaire, Jean-Marie Peloponese
Global dysregulation of microRNAs (miRNAs), a class of non-coding RNAs that regulate genes expression, is a common feature of human tumors. Profiling of cellular miRNAs on Adult T cell Leukemia (ATL) cells by Yamagishi et al. showed a strong decrease in expression for 96.7% of cellular miRNAs in ATL cells. However, the mechanisms that regulate the expression of miRNAs in ATL cells are still largely unknown. In this study, we compared the expression of 12 miRs previously described for being overexpress by Tax and the expression of several key components of the miRNAs biogenesis pathways in different HBZ expressing cell lines as well as in primary CD4 (+) cells from acute ATL patients...
May 24, 2016: Oncotarget
https://www.readbyqxmd.com/read/26799480/targeting-epigenetic-regulators-for-cancer-therapy-modulation-of-bromodomain-proteins-methyltransferases-demethylases-and-micrornas
#17
Kathy A Gelato, Zaki Shaikhibrahim, Matthias Ocker, Bernard Haendler
INTRODUCTION: Histone deacetylases (HDACs) and DNA methyltransferases (DNMTs) were the first epigenetic targets to be successfully addressed for cancer treatment, but more recently additional families of epigenetic modulators have been the subject of intense research. Potent inhibitors have been identified in several instances and have proven to be invaluable tools for studying these proteins in normal physiology and in disease. Some have now progressed to clinical studies in hematological and solid tumors, and encouraging early results have been reported...
July 2016: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/26773213/resetting-the-epigenome-for-heart-regeneration
#18
REVIEW
Gregory A Quaife-Ryan, Choon Boon Sim, Enzo R Porrello, James E Hudson
In contrast to adults, recent evidence suggests that neonatal mice are able to regenerate following cardiac injury. This regenerative capacity is reliant on robust induction of cardiomyocyte proliferation, which is required for faithful regeneration of the heart following injury. However, cardiac regenerative potential is lost as cardiomyocytes mature and permanently withdraw from the cell cycle shortly after birth. Recently, a handful of factors responsible for the regenerative disparity between the adult and neonatal heart have been identified, but the proliferative response of adult cardiomyocytes following modulation of these factors rarely reaches neonatal levels...
October 2016: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/26747785/mir-185-mediates-lung-epithelial-cell-death-after-oxidative-stress
#19
Duo Zhang, Heedoo Lee, Yong Cao, Charles S Dela Cruz, Yang Jin
Lung epithelial cell death is a prominent feature involved in the development of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Hyperoxia-induced ALI is an established animal model mimicking human ARDS. Small noncoding RNAs such as microRNAs (miRNAs) have potent physiological and pathological functions involving multiple disease processes. Emerging interests focus on the potential of miRNAs to serve as novel therapeutic targets and diagnostic biomarkers. We found that hyperoxia highly induces miR-185 and its precursor in human lung epithelial cells in a time-dependent manner, and this observation is confirmed using mouse primary lung epithelial cells...
April 1, 2016: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/26676759/myc-induces-mirna-mediated-apoptosis-in-response-to-hdac-inhibition-in-hematologic-malignancies
#20
Clare M Adams, Scott W Hiebert, Christine M Eischen
Alterations in the expression or function of histone deacetylases (HDAC) contribute to the development and progression of hematologic malignancies. Consequently, the development and implementation of HDAC inhibitors has proven to be therapeutically beneficial, particularly for hematologic malignancies. However, the molecular mechanisms by which HDAC inhibition (HDACi) induces tumor cell death remain unresolved. Here, we investigated the effects of HDACi in Myc-driven B-cell lymphoma and five other hematopoietic malignancies...
February 1, 2016: Cancer Research
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