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https://www.readbyqxmd.com/read/29318382/mir-29-silencing-modulates-the-expression-of-target-genes-related-to-proliferation-apoptosis-and-methylation-in-burkitt-lymphoma-cells
#1
Luciano Mazzoccoli, Marcela Cristina Robaina, Alexandre Gustavo Apa, Martin Bonamino, Luciana Wernersbach Pinto, Eduardo Queiroga, Carlos E Bacchi, Claudete Esteves Klumb
PURPOSE: Burkitt lymphoma (BL) is a B-cell lymphoma frequently diagnosed in children. It is characterized by MYC translocations, which lead to the constitutive expression of the MYC oncogene. MYC contributes to miR-29 repression through an E-box MYC binding site on the miR-29b-1/miR-29a promoter region. We evaluated the role of miR-29a/b/c and their predicted targets in BL pathogenesis. METHODS: Mature sequences of miR-29a/b/c were transfected to the BL cell lines BL41 and Raji, and evaluated for DNMT3B, MCL1, BIM, CDK6, AKT and TCL1 protein expression as well as for MCL-1 and CDK6 mRNA expression...
January 9, 2018: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/29290969/low-plasma-levels-of-mir-101-are-associated-with-tumor-progression-in-gastric-cancer
#2
Taisuke Imamura, Shuhei Komatsu, Daisuke Ichikawa, Mahito Miyamae, Wataru Okajima, Takuma Ohashi, Jun Kiuchi, Keiji Nishibeppu, Toshiyuki Kosuga, Hirotaka Konishi, Atsushi Shiozaki, Kazuma Okamoto, Hitoshi Fujiwara, Eigo Otsuji
Background: Several studies have identified the decreased expression of the tumor suppressor miR-101 in various cancers. In this study, we tested miR-101 as a potential therapeutic target and novel plasma biomarker for gastric cancer (GC). Results: The miR-101 expression level was significantly lower in GC tissues (P = 0.0038) and GC cell lines (P = 0.0238) than in normal gastric mucosa. Both exosomal and plasma miR-101 were significantly downregulated in GC patients compared with healthy volunteers (P = 0...
December 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/29275301/cycloartobiloxanthone-induces-human-lung-cancer-cell-apoptosis-via-mitochondria-dependent-apoptotic-pathway
#3
Nattanan Losuwannarak, Boonchoo Sritularak, Pithi Chanvorachote
BACKGROUND: Lung cancer is one of most malignant types of cancer and new anticancer agents are still required. Cycloartobiloxanthone, a flavonoid isolated from stem bark of Artocarpus gomezianus, has potential for being developed for anticancer therapy. MATERIALS AND METHODS: Cytotoxicity of cycloartobiloxanthone was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) assay against four human lung cancer cell lines (H23, H460, H292 and A549) and their half-maximal inhibitory concentrations (IC50) were assessed...
January 2018: In Vivo
https://www.readbyqxmd.com/read/29258623/dynamic-modeling-of-folliculogenesis-signaling-pathways-in-the-presence-of-mirnas-expression
#4
Abolfazl Bahrami, Seyed Reza Miraie-Ashtiani, Mostafa Sadeghi, Ali Najafi, Reza Ranjbar
BACKGROUND: TEK signaling plays a very important role in folliculogenesis. It activates Ras/ERK/MYC, PI3K/AKT/mTORC1 and ovarian steroidogenesis activation pathways. These are the main pathways for cell growth, differentiation, migration, adhesion, proliferation, survival and protein synthesis. RESULTS: TEK signaling on each of the two important pathways where levels of pERK, pMYC, pAkt, pMCL1 and pEIF4EBP1 are increased in dominant follicles and pMYC is decreased in dominant follicles...
December 19, 2017: Journal of Ovarian Research
https://www.readbyqxmd.com/read/29205703/lncrna-neat1-promotes-dexamethasone-resistance-in-multiple-myeloma-by-targeting-mir-193a-mcl1-pathway
#5
Yilan Wu, Han Wang
Although dexamethasone (DEX) remains a first-line agent for multiple myeloma (MM) therapy, the development of DEX resistance has become an indicator of poor prognosis in MM patients. It is thus urgent to develop strategies to restore the vulnerability of MM to DEX. This study demonstrated long non-coding RNA (lncRNA) nuclear paraspeckle assembly transcript 1 (NEAT1) was highly expressed in DEX-resistant myeloma cell lines, and upregulation of NEAT1 was tightly linked to poor prognosis. The in-depth study revealed that during the development of DEX resistance in these cells, the miR-193a levels were decreased, which resulted in the increased expression of the target gene myeloid cell leukemia-1 (MCL1)...
December 4, 2017: Journal of Biochemical and Molecular Toxicology
https://www.readbyqxmd.com/read/29189162/tunneling-nanotubes-a-versatile-target-for-cancer-therapy
#6
Pragyaparamita Sahoo, Soumya Ranjan Jena, Luna Samanta
Acute Myeloid Leukemia (AML) and Acute Lymphocytic Leukemia (ALL) are common acute leukemia in adults and children respectively. In therapy process of these malignancies, chemotherapy is the main strategy that fails in many of cases. Moreover, chemotherapy is usually associated with adverse effects it also damages the healthy cells. In this regard, development of new therapies is essential. Monoclonal antibodies directed to the cell surface markers of leukemic blasts may have promising consequences. These tools can provide a specific cell targeting with minimal toxic effects on other normal cells...
November 29, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/29187422/dependency-of-heterochromatin-domains-on-replication-factors
#7
Leonie Johanna Jahn, Bethany Mason, Peter Brøgger, Tea Toteva, Dennis Kim Nielsen, Genevieve Thon
Chromatin structure regulates both genome expression and dynamics in eukaryotes where large heterochromatic regions are epigenetically silenced through the methylation of histone H3K9, histone deacetylation, and assembly of repressive complexes. Previous genetic screens with the fission yeast Schizosaccharomyces pombe have led to the identification of key enzymatic activities and structural constituents of heterochromatin. We report here on additional factors discovered by screening a library of deletion mutants for silencing defects at the edge of a heterochromatic domain bound by its natural boundary - the IR-R+ element - or by ectopic boundaries...
November 29, 2017: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/29183729/mir-596-modulates-melanoma-growth-by-regulating-cell-survival-and-death
#8
Szu-Mam Liu, Chen-Huan Lin, Jean Lu, In-Yu Lin, Mu-Shiun Tsai, Ming-Hong Chen, Nianhan Ma
Tumors grow because cancer cells lack the ability to balance cell survival and death signaling pathways. miR-596, a microRNA located at the 8p23.3 locus, has been shown by the TCGA-Assembler to be deleted in a significant number of melanoma samples. Here, we also validated the low levels of miR-596 in melanoma compared to tissue nevi, and Kaplan-Meier curve analysis revealed that low miR-596 expression was associated with worse overall survival. Moreover, we showed that miR-596 overexpression effectively inhibited MAPK/ERK signaling, cell proliferation, migration, and invasion and increased the cell apoptosis of melanoma cells...
November 25, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/29173002/mir-509-3p-promotes-cisplatin-induced-apoptosis-in-ovarian-cancer-cells-through-the-regulation-of-anti-apoptotic-genes
#9
Wei Chen, Jingjie Du, Xiaodi Li, Jiancheng Su, Yongzhi Huang, Nan Ding, Mengdie Zhang, Songshan Jiang
AIM: Previous observations have implicated miR-509-3p's ability in regulating cisplatin-triggered apoptosis in ovarian cancer. However, the underlying mechanisms were not fully understood. MATERIALS & METHODS: The roles of miR-509-3p in cellular apoptosis were assessed through MTT and DAPI assays. The confirmation of the regulation of BCL2 family members by miR-509-3p was investigated by luciferase reporter assay, western blot, quantitative real-time PCR and rescue experiments...
November 27, 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/29152113/the-prognostic-significance-of-mcl1-copy-number-gain-in-esophageal-squamous-cell-carcinoma
#10
Chen Xu, Yalan Liu, Jie Huang, Hao Wang, Lijie Tan, Yifan Xu, Zhengzeng Jiang, Xin Wang, Yingyong Hou, Dongxian Jiang, Qun Wang
Background: MCL1 copy number variations have been reported to be associated with cancer prognosis in several cancers. However, the role of MCL1 gain has not yet been determined in esophageal squamous cell carcinomas (ESCC). Methods: Fluorescence in situ hybridization (FISH) for MCL1 was performed on 262 ESCC samples using tissue microarray (TMA). Results: The median age of ESCC patients was 62 years (range 37-83), with frequencies between women (16...
October 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/29118074/golgi-stress-induced-transcriptional-changes-mediated-by-mapk-signaling-and-three-ets-transcription-factors-regulate-mcl1-splicing
#11
Jan Baumann, Tatiana I Ignashkova, Sridhar R Chirasani, Silvia Ramírez-Peinado, Hamed Alborzinia, Mathieu Gendarme, Kyra Kuhnigk, Valentin Kramer, Ralph K Lindemann, Jan H Reiling
The secretory pathway is a major determinant of cellular homoeostasis. While research into secretory stress signaling has so far mostly focused on the ER, emerging data suggests that the Golgi itself serves as an important signaling hub capable of initiating stress responses. To systematically identify novel Golgi stress mediators, we performed a transcriptomic analysis of cells exposed to three different pharmacological compounds known to elicit Golgi fragmentation: brefeldin A (BFA), golgicide A (GCA) and monensin (MON)...
November 8, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/29072681/demethylzeylasteral-inhibits-cell-proliferation-and-induces-apoptosis-through-suppressing-mcl1-in-melanoma-cells
#12
Yuzu Zhao, Jiang He, Jun Li, Xingzhi Peng, Xianxing Wang, Zhen Dong, Erhu Zhao, Yaling Liu, Zonghui Wu, Hongjuan Cui
Demethylzeylasteral is one of the extracts of Tripterygium wilfordii Hook F, which plays important roles in multiple biological processes such as inflammation inhibition, as well as immunosuppression. However, anti-cancer function and the underlying mechanisms of demethylzeylasteral in melanoma cells remain unclear. In this study, we demonstrate that demethylzeylasteral has an anti-tumor property in melanoma cells. Demethylzeylasteral not only inhibits cell proliferation through cell cycle arrest at S phase, but also induces cell apoptosis in melanoma cells...
October 26, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/29063678/molecular-profiling-and-combinatorial-activity-of-cct068127-a-potent-cdk2-and-cdk9-inhibitor
#13
Steven R Whittaker, Clare Barlow, Mathew P Martin, Caterina Mancusi, Steve Wagner, Annette Self, Elaine Barrie, Robert Te Poele, Swee Sharp, Nathan Brown, Stuart Wilson, Wayne Jackson, Peter M Fischer, Paul A Clarke, Michael I Walton, Edward McDonald, Julian Blagg, Martin Noble, Michelle D Garrett, Paul Workman
Deregulation of the cyclin-dependent kinases (CDKs) has been implicated in the pathogenesis of multiple cancer types. Consequently, CDKs have garnered intense interest as therapeutic targets for the treatment of cancer. We describe herein the molecular and cellular effects of CCT068127, a novel inhibitor of CDK2 and CDK9. Optimised from the purine template of seliciclib, CCT068127 exhibits greater potency and selectivity against purified CDK2 and CDK9 and superior antiproliferative activity against human colon cancer and melanoma cell lines...
October 24, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/29024646/the-epstein-barr-virus-regulome-in-lymphoblastoid-cells
#14
Sizun Jiang, Hufeng Zhou, Jun Liang, Catherine Gerdt, Chong Wang, Liangru Ke, Stefanie C S Schmidt, Yohei Narita, Yijie Ma, Shuangqi Wang, Tyler Colson, Benjamin Gewurz, Guoliang Li, Elliott Kieff, Bo Zhao
Epstein-Barr virus (EBV) transforms B cells to continuously proliferating lymphoblastoid cell lines (LCLs), which represent an experimental model for EBV-associated cancers. EBV nuclear antigens (EBNAs) and LMP1 are EBV transcriptional regulators that are essential for LCL establishment, proliferation, and survival. Starting with the 3D genome organization map of LCL, we constructed a comprehensive EBV regulome encompassing 1,992 viral/cellular genes and enhancers. Approximately 30% of genes essential for LCL growth were linked to EBV enhancers...
October 11, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/29018077/efficacy-of-venetoclax-as-targeted-therapy-for-relapsed-refractory-t-11-14-multiple-myeloma
#15
Shaji Kumar, Jonathan L Kaufman, Cristina Gasparetto, Joseph Mikhael, Ravi Vij, Brigitte Pegourie, Lofti Benboubker, Thierry Facon, Martine Amiot, Philippe Moreau, Elizabeth A Punnoose, Stefanie Alzate, Martin Dunbar, Tu Xu, Suresh K Agarwal, Sari Heitner Enschede, Joel D Leverson, Jeremy A Ross, Paulo C Maciag, Maria Verdugo, Cyrille Touzeau
Venetoclax is a selective, orally bioavailable BCL-2 inhibitor that induces cell death in MM cells, particularly in those harboring t(11;14), which express high levels of BCL-2 relative to BCL-XL and MCL-1. In this phase I study, patients with relapsed/refractory MM received venetoclax monotherapy. After a 2-week lead-in with weekly dose escalation, daily venetoclax was given at 300, 600, 900, or 1200 mg in dose-escalation cohorts and 1200 mg in the safety expansion. Dexamethasone could be added upon progression during treatment...
October 10, 2017: Blood
https://www.readbyqxmd.com/read/28978427/myc-and-mcl1-cooperatively-promote-chemotherapy-resistant-breast-cancer-stem-cells-via-regulation-of-mitochondrial-oxidative-phosphorylation
#16
Kyung-Min Lee, Jennifer M Giltnane, Justin M Balko, Luis J Schwarz, Angel L Guerrero-Zotano, Katherine E Hutchinson, Mellissa J Nixon, Mónica V Estrada, Violeta Sánchez, Melinda E Sanders, Taekyu Lee, Henry Gómez, Ana Lluch, J Alejandro Pérez-Fidalgo, Melissa Magdalene Wolf, Gabriela Andrejeva, Jeffrey C Rathmell, Stephen W Fesik, Carlos L Arteaga
Most patients with advanced triple-negative breast cancer (TNBC) develop drug resistance. MYC and MCL1 are frequently co-amplified in drug-resistant TNBC after neoadjuvant chemotherapy. Herein, we demonstrate that MYC and MCL1 cooperate in the maintenance of chemotherapy-resistant cancer stem cells (CSCs) in TNBC. MYC and MCL1 increased mitochondrial oxidative phosphorylation (mtOXPHOS) and the generation of reactive oxygen species (ROS), processes involved in maintenance of CSCs. A mutant of MCL1 that cannot localize in mitochondria reduced mtOXPHOS, ROS levels, and drug-resistant CSCs without affecting the anti-apoptotic function of MCL1...
October 3, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28974650/inhibition-of-the-oncogenic-fusion-protein-ews-fli1-causes-g2-m-cell-cycle-arrest-and-enhanced-vincristine-sensitivity-in-ewing-s-sarcoma
#17
Stefan K Zöllner, Saravana P Selvanathan, Garrett T Graham, Ryan M T Commins, Sung Hyeok Hong, Eric Moseley, Sydney Parks, Jessica N Haladyna, Hayriye V Erkizan, Uta Dirksen, Michael D Hogarty, Aykut Üren, Jeffrey A Toretsky
Ewing's sarcoma (ES) is a rare and highly malignant cancer that grows in the bones or surrounding tissues mostly affecting adolescents and young adults. A chimeric fusion between the RNA binding protein EWS and the ETS family transcription factor FLI1 (EWS-FLI1), which is generated from a chromosomal translocation, is implicated in driving most ES cases by modulation of transcription and alternative splicing. The small-molecule YK-4-279 inhibits EWS-FLI1 function and induces apoptosis in ES cells. We aimed to identify both the underlying mechanism of the drug and potential combination therapies that might enhance its antitumor activity...
October 3, 2017: Science Signaling
https://www.readbyqxmd.com/read/28966941/increased-expression-of-the-tight-junction-protein-tjp1-zo-1-is-associated-with-upregulation-of-taz-tead-activity-and-an-adult-tissue-stem-cell-signature-in-carfilzomib-resistant-multiple-myeloma-cells-and-high-risk-multiple-myeloma-patients
#18
Irene Riz, Robert G Hawley
Tight junction protein 1 (TJP1) has recently been proposed as a biomarker to identify multiple myeloma (MM) patients most likely to respond to bortezomib- and carfilzomib-based proteasome inhibitor regimens. Herein we report increased expression of TJP1 during the adaptive response mediating carfilzomib resistance in the LP-1/Cfz MM cell line. Moreover, increased TJP1 expression delineated a subset of relapsed/refractory MM patients on bortezomib-based therapy sharing an LP-1/Cfz-like phenotype characterized by activation of interacting transcriptional effectors of the Hippo signaling cascade (TAZ and TEAD1) and an adult tissue stem cell signature...
July 2017: Oncoscience
https://www.readbyqxmd.com/read/28945224/rarf-confers-ra-resistance-by-sequestering-rar-to-the-nucleolus-and-regulating-mcl1-in-leukemia-cells
#19
H Youn, H-K Lee, H-R Sohn, U-H Park, E-J Kim, B Youn, S-J Um
Retinoic acid (RA) has broad clinical applications for the treatment of various cancers, particularly acute promyelocytic leukemia. However, RA-based therapy is limited by relapse in patients associated with RA resistance, the mechanism of which is poorly understood. Here, we suggest a new molecular mechanism of RA resistance by a repressor, named RA resistance factor (RaRF). RaRF suppressed transcriptional activity of the RA receptor (RAR) by directly interacting with and sequestering RAR to the nucleolus in response to RA...
September 25, 2017: Oncogene
https://www.readbyqxmd.com/read/28939105/protein-kinase-c-eta-regulates-mcl-1-level-via-erk1
#20
Deepanwita Pal, Alakananda Basu
Protein kinase C (PKC)-eta (PKCη) is a member of the novel category of PKC family. It is overexpressed in breast cancer and was shown to inhibit apoptosis and contribute to chemoresistance. Since the anti-apoptotic Bcl-2 family protein myeloid cell leukemia-1 (Mcl-1) plays an important role in breast cancer cell survival and chemoresistance, we investigated if PKCη regulates Mcl-1 level. Silencing of PKCη decreased Mcl-1 in several breast cancer cells, including MCF-7 and T47D cells. PKCη depletion had no effect on MCL1 mRNA but the decrease in Mcl-1 by PKCη knockdown was blocked by proteasomal inhibitors, such as MG132 and lactacystin...
December 2017: Cellular Signalling
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