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https://www.readbyqxmd.com/read/28423601/a-novel-lncrna-gasl1-inhibits-cell-proliferation-and-restricts-e2f1-activity
#1
Lital Gasri-Plotnitsky, Aviv Ovadia, Katerina Shamalov, Tali Nizri-Megnaji, Shimrit Meir, Irit Zurer, Cyrille J Cohen, Doron Ginsberg
The human genome encodes thousands of unique long non-coding RNAs (lncRNAs), many of which are emerging as critical regulators of cell fate. However, their functions as well as their transcriptional regulation are only partially understood. The E2F1 transcription factor induces both proliferation and apoptosis, and is a critical downstream target of the tumor suppressor, RB. Here, we provide evidence that a novel lncRNA named GASL1 is transcriptionally regulated by E2F1; GASL1 levels are elevated upon activation of exogenous E2F1 or endogenous E2Fs...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28413473/microrna-200c-suppresses-cell-growth-and-metastasis-by-targeting-bmi-1-and-e2f3-in-renal-cancer-cells
#2
Mingning Qiu, Ziji Liang, Lieqian Chen, Guobin Tan, Lei Liu, Kangning Wang, Hege Chen, Jianjun Liu
The aim of the present study was to evaluate the functions of miR-200c in the regulation of tumor growth and metastasis in renal cancer cells, and to investigate the underlying mechanisms. In this study, miR-200c was up- and downregulated in two renal cancer cell lines, namely ACHN and A498, and the proliferation, colony formation, migration and invasion of the cells were measured. The expression levels of various mRNAs and proteins were then analyzed using reverse transcription-quantitative polymerase chain reaction and western blotting, respectively...
April 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28404959/inhibition-of-the-prolyl-isomerase-pin1-enhances-the-ability-of-sorafenib-to-induce-cell-death-and-inhibit-tumor-growth-in-hepatocellular-carcinoma
#3
Min Zheng, Huijuan Xu, Xin-Hua Liao, Champ Peng Chen, Arina Li Zhang, Wenxian Lu, Long Wang, Dayun Yang, Jichuang Wang, Hekun Liu, Xiao Zhen Zhou, Kun Ping Lu
Hepatocellular carcinoma (HCC) is the sixth most common cancer, but is the second leading cause of cancer deaths, partially due to its heterogeneity and drug resistance. Sorafenib is the only medical treatment with a proven efficacy against advanced HCC, but its overall clinical efficacy is still modest. Therefore, a major challenge is how to improve its therapeutic efficacy. The unique prolyl isomerase Pin1 regulates numerous cancer-driving pathways. Notably, Pin1 is overexpressed in about 70% HBV-positive HCC patients and contributes to HCC tumorigenesis...
March 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28381640/early-b-cell-progenitors-deficient-for-gon4l-fail-to-differentiate-due-to-a-block-in-mitotic-cell-division
#4
Jennifer Y Barr, Renee X Goodfellow, Diana F Colgan, John D Colgan
B cell development in Justy mutant mice is blocked due to a precursor mRNA splicing defect that depletes the protein GON4-like (GON4L) in B cell progenitors. Genetic and biochemical studies have suggested that GON4L is a transcriptional regulator that coordinates cell division with differentiation, but its role in B cell development is unknown. To understand the function of GON4L, we characterized B cell differentiation, cell cycle control, and mitotic gene expression in GON4L-deficient B cell progenitors from Justy mice...
April 5, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28378447/a-genome-wide-linkage-and-association-analysis-of-imputed-insertions-and-deletions-with-cardiometabolic-phenotypes-in-mexican-americans-the-insulin-resistance-atherosclerosis-family-study
#5
Chuan Gao, Fang-Chi Hsu, Latchezar M Dimitrov, Hayrettin Okut, Yii-Der I Chen, Kent D Taylor, Jerome I Rotter, Carl D Langefeld, Donald W Bowden, Nicholette D Palmer
Insertions and deletions (INDELs) represent a significant fraction of interindividual variation in the human genome yet their contribution to phenotypes is poorly understood. To confirm the quality of imputed INDELs and investigate their roles in mediating cardiometabolic phenotypes, genome-wide association and linkage analyses were performed for 15 phenotypes with 1,273,952 imputed INDELs in 1,024 Mexican-origin Americans. Imputation quality was validated using whole exome sequencing with an average kappa of 0...
April 5, 2017: Genetic Epidemiology
https://www.readbyqxmd.com/read/28371821/telomerase-activation-in-posterior-fossa-group-a-ependymomas-is-associated-with-dismal-prognosis-and-chromosome-1q-gain
#6
Johannes Gojo, Daniela Lötsch, Sabine Spiegl-Kreinecker, Kristian W Pajtler, Katharina Neumayer, Pia Korbel, Asuka Araki, Anita Brandstetter, Thomas Mohr, Volker Hovestadt, Lukas Chavez, Dominik Kirchhofer, Gerda Ricken, Harald Stefanits, Andrey Korshunov, Stefan M Pfister, Karin Dieckmann, Amedeo A Azizi, Thomas Czech, Martin Filipits, Marcel Kool, Andreas Peyrl, Irene Slavc, Walter Berger, Christine Haberler
Background.: Ependymomas account for up to 10% of childhood CNS tumors and have a high rate of tumor recurrence despite gross total resection. Recently, classification into molecular ependymoma subgroups has been established, but the mechanisms underlying the aggressiveness of certain subtypes remain widely enigmatic. The aim of this study was to dissect the clinical and biological role of telomerase reactivation, a frequent mechanism of cancer cells to evade cellular senescence, in pediatric ependymoma...
March 24, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28370296/validation-of-a-multiplexed-gene-signature-assay-for-diagnosis-of-canine-cancers-from-formalin-fixed-paraffin-embedded-tissues
#7
B Davis, M Schwartz, D Duchemin, J Carl Barrett, G Post
BACKGROUND: Use of molecular-based diagnostics for companion animals is impeded by availability of technology platforms, tissue acquisition requirements, and species-specific reagents. HYPOTHESIS/OBJECTIVES: To validate a quantitative nuclease protection assay (qNPA) to simultaneously measure RNA expression of multiple genes in archived formalin-fixed paraffin-embedded (FFPE) tumors from dogs. ANIMALS: All tumor biopsy samples were collected retrospectively from surgical biopsies and in the care of veterinarians...
March 29, 2017: Journal of Veterinary Internal Medicine
https://www.readbyqxmd.com/read/28368473/targeting-myc-as-a-therapeutic-intervention-for-anaplastic-thyroid-cancer
#8
Keisuke Enomoto, Xuguang Zhu, Sunmi Park, Li Zhao, Yuelin J Zhu, Mark C Willingham, Jun Qi, John A Copland, Paul Meltzer, Sheue-Yann Cheng
Context: Recent studies showed that transcription of the MYC gene is driven by interaction of bromodomain and extraterminal domain (BET) proteins with acetylated histones on chromatin. A potent inhibitor, JQ1, which effectively disrupts the interaction of BET proteins with acetylated histones, preferentially suppresses transcription of the MYC gene. We recently reported that JQ1 decreased thyroid tumor growth and improved survival in a mouse model of anaplastic thyroid cancer (ATC) by targeting MYC transcription...
March 28, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28362317/microrna-17-92-regulates-the-transcription-factor-e2f3b-during-myogenesis-in-vitro-and-in-vivo
#9
Zhixiong Tang, Nian Liu, Lan Luo, Kang Kang, Li Li, Ruiyang Ni, Huiling Qiu, Deming Gou
Myogenic differentiation, which occurs during muscle development, is a highly ordered process that can be regulated by E2F transcription factors. Available data show that E2F3b, but not E2F3a, is upregulated and required for myogenic differentiation. However, the regulation of E2F3b expression in myogenic differentiation is not well understood. To investigate whether E2Fb expression is controlled by miRNAs, we used bioinformatics to combine the database of microRNAs downregulated during myogenesis and those predicted to target E2F3...
March 31, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28345026/oncolytic-adenoviruses-armed-with-tumor-necrosis-factor-alpha-and-interleukin-2-enable-successful-adoptive-cell-therapy
#10
Riikka Havunen, Mikko Siurala, Suvi Sorsa, Susanna Grönberg-Vähä-Koskela, Michael Behr, Siri Tähtinen, João Manuel Santos, Pauliina Karell, Juuso Rusanen, Dirk M Nettelbeck, Anja Ehrhardt, Anna Kanerva, Akseli Hemminki
Adoptive cell therapy holds much promise in the treatment of cancer but results in solid tumors have been modest. The notable exception is tumor-infiltrating lymphocyte (TIL) therapy of melanoma, but this approach only works with high-dose preconditioning chemotherapy and systemic interleukin (IL)-2 postconditioning, both of which are associated with toxicities. To improve and broaden the applicability of adoptive cell transfer, we constructed oncolytic adenoviruses coding for human IL-2 (hIL2), tumor necrosis factor alpha (TNF-α), or both...
March 17, 2017: Molecular Therapy Oncolytics
https://www.readbyqxmd.com/read/28337965/knockdown-of-e2f3-inhibits-proliferation-migration-and-invasion-and-increases-apoptosis-in-glioma-cells
#11
Zhi-Gang Shen, Xiao-Zhou Liu, Chang-Xiu Chen, Jing-Min Lu
E2F3a as a member of E2F family is essential for cell division associated with the progressing of many cancers. Whereas, the biological effects of E2F3a on glioma is less understood. To investigate the functional mechanism of E2F3a in glioma, we examined the expression of E2F3a in glioma tissues and cell lines. We found that E2F3a was upregulated in glioma tissues compared with adjacent tissues and associated a poor survival time. E2F3a was highly expressed in glioma cell lines compared with normal HEB cell lines...
March 23, 2017: Oncology Research
https://www.readbyqxmd.com/read/28320735/the-retinoblastoma-homolog-rbr1-mediates-localization-of-the-repair-protein-rad51-to-dna-lesions-in-arabidopsis
#12
Sascha Biedermann, Hirofumi Harashima, Poyu Chen, Maren Heese, Daniel Bouyer, Kostika Sofroni, Arp Schnittger
The retinoblastoma protein (Rb), which typically functions as a transcriptional repressor of E2F-regulated genes, represents a major control hub of the cell cycle. Here, we show that loss of the Arabidopsis Rb homolog RETINOBLASTOMA-RELATED 1 (RBR1) leads to cell death, especially upon exposure to genotoxic drugs such as the environmental toxin aluminum. While cell death can be suppressed by reduced cell-proliferation rates, rbr1 mutant cells exhibit elevated levels of DNA lesions, indicating a direct role of RBR1 in the DNA-damage response (DDR)...
March 20, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28302719/a-repressive-role-of-enhancer-of-zeste-homolog-2-in-11%C3%AE-hydroxysteroid-dehydrogenase-type-2-expression-in-human-placenta
#13
Rujuan Zuo, Xiaohui Liu, Wangsheng Wang, Wenjiao Li, Hao Ying, Kang Sun
The expression of 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2), which acts as a placental glucocorticoid barrier, is silenced in the cytotrophoblasts but substantially up-regulated during syncytialization. However, the repressive mechanism of 11β-HSD2 expression before syncytialization and how this repression is lifted during syncytialization remain mostly unresolved. Here we found that enhancer of zeste homolog 2 (EZH2) accounts for the silence of 11β-HSD2 expression via trimethylation of histone H3 lysine 27 (H3K27me3) at the promoter of 11β-HSD2 gene...
March 16, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28297760/-promoting-effect-of-cyclin-d1-overexpression-on-proliferation-and-epithelial-mesenchymal-transition-of-cervical-squamous-cell-carcinoma-siha-cells
#14
P Wang, S Liu, B Cheng, X Z Wu, S S Ding, L Xu, Y Liu, L Duan, S Z Sun
Objective: To study effects of cyclin D1 overexpression on the proliferation and differentiation of cervical squamous cell carcinoma SiHa cells and to investigate related signaling molecules. Methods: Primers were designed to amplify the full length of cyclin D1 gene and cyclin D1 gene was amplified by PCR for constructing pcDNA3.1 plasmid vector. The construct was then transfected into SiHa cells, and the cells with stable overexpression of cyclin D1 were established, cyclin D1 gene and protein expression were detected by RT-PCR and Western blot, respectively...
March 8, 2017: Zhonghua Bing Li Xue za Zhi Chinese Journal of Pathology
https://www.readbyqxmd.com/read/28293272/multiple-molecular-interactions-redundantly-contribute-to-rb-mediated-cell-cycle-control
#15
Michael J Thwaites, Matthew J Cecchini, Srikanth Talluri, Daniel T Passos, Jasmyne Carnevale, Frederick A Dick
BACKGROUND: The G1-S phase transition is critical to maintaining proliferative control and preventing carcinogenesis. The retinoblastoma tumor suppressor is a key regulator of this step in the cell cycle. RESULTS: Here we use a structure-function approach to evaluate the contributions of multiple protein interaction surfaces on pRB towards cell cycle regulation. SAOS2 cell cycle arrest assays showed that disruption of three separate binding surfaces were necessary to inhibit pRB-mediated cell cycle control...
2017: Cell Division
https://www.readbyqxmd.com/read/28289097/human-cytomegalovirus-v-cdk-ul97-phosphorylates-and-inactivates-the-retinoblastoma-protein-related-p107-and-p130-proteins
#16
Satoko Iwahori, Angie C Umaña, Halena R VanDeusen, Robert F Kalejta
The human cytomegalovirus (HCMV)-encoded viral cyclin-dependent kinase (v-CDK) UL97 phosphorylates the retinoblastoma (Rb) tumor suppressor. Here we identify the other Rb family members p107 and p130 as novel targets of UL97. UL97 phosphorylates p107 and p130 thereby inhibiting their ability to repress the E2F-responsive E2F1 promoter. As with Rb, this phosphorylation, and the rescue of E2F-responsive transcription, is dependent on the L1 LXCXE motif in UL97 and its interacting clefts on p107 and p130. Interestingly, UL97 does not induce the disruption of all p107-E2F or p130-E2F complexes, as it does to Rb-E2F complexes...
March 13, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28270497/neopalana-neoadjuvant-palbociclib-a-cyclin-dependent-kinase-4-6-inhibitor-and-anastrozole-for-clinical-stage-2-or-3-estrogen-receptor-positive-breast-cancer
#17
Cynthia X Ma, Feng Gao, Jingqin Luo, Donald W Northfelt, Matthew P Goetz, Andres Forero, Jeremy Hoog, Michael J Naughton, Foluso Ademuyiwa, Rama Suresh, Karen S Anderson, Julie Margenthaler, Rebecca Aft, Timothy J Hobday, Timothy Moynihan, William Gillanders, Amy Cyr, Timothy J Eberlein, Tina Hieken, Helen Krontiras, Zhanfang Guo, Michelle Lee, Nicholas C Spies, Zachary L Skidmore, Obi L Griffith, Malachi Griffith, Shana Thomas, Caroline Bumb, Kiran Vij, Cynthia Huang Bartlett, Maria Koehler, Hussam Al-Kateb, Souzan Sanati, Matthew J Ellis
PURPOSE: Cyclin-dependent kinase (CDK) 4/6 drives cell proliferation in estrogen receptor positive (ER+) breast cancer. This single-arm phase II neoadjuvant trial (NeoPalAna) assessed the anti-proliferative activity of the CDK4/6 inhibitor palbociclib in primary breast cancer as a prelude to adjuvant studies. EXPERIMENTAL DESIGN: Eligible patients with clinical stage II/III ER+/HER2- breast cancer received anastrozole 1mg daily for 4 weeks (cycle 0) (with goserelin if premenopausal), followed by adding palbociclib (125mg daily on days 1-21) on cycle 1 day 1 (C1D1) for four 28-day cycles unless C1D15 Ki67>10%, in which case patients went off study due to inadequately response...
March 7, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28270228/e2f8-a-direct-target-of-mir-144-promotes-papillary-thyroid-cancer-progression-via-regulating-cell-cycle
#18
Jing Sun, Run Shi, Sha Zhao, Xiaona Li, Shan Lu, Hemei Bu, Xianghua Ma, Chuan Su
BACKGROUND: Thyroid cancer is the most common malignancy of endocrine system, and papillary thyroid cancer (PTC) is the most common subtype. E2F8, a novel identified E2F family member, was reported to associate with progression of several human cancers, however, its clinical significance and biological role in PTC remain unknown. METHODS: E2F8 or miR-144 expression profiles in PTC tissues were obtained from The Cancer Genome Atlas (TCGA) datasets, and the correlation of E2F8 expression with clinicopathological features was analyzed in a cohort PTC patients...
March 7, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28260085/roles-of-immune-inhibitory-molecule-b7-h4-in-cervical-cancer
#19
Sai Han, Yi Li, Jingjing Zhang, Lu Liu, Qian Chen, Qiuhong Qian, Shan Li, Youzhong Zhang
Recent studies have reported that the immune-regulatory protein B7-H4 is highly expressed in various types of cancer, but little is known concerning its roles in cervical cancer. In the present study, we investigated the expression of B7-H4 in human tissues and serum samples, and explored the effects of B7-H4 on proliferation, apoptosis, migration and invasion of cervical cancer cell lines, including SiHa and HeLa. We found that B7-H4 was mainly located in the cytoplasm of cervical cancer cells as determined by immunofluorescence staining...
April 2017: Oncology Reports
https://www.readbyqxmd.com/read/28259945/rb-deficiency-accelerates-progression-of-carcinoma-of-the-urinary-bladder-in-vivo-and-in-vitro-through-inhibiting-autophagy-and-apoptosis
#20
Cheng-Yuan Wang, Zhi-Bin Xu, Jiang-Ping Wang, Yong Jiao, Bo Zhang
Urinary bladder cancer is known as a common cancer diagnosed across the world and results in significant mortality and morbidity rates among patients. The retinoblastoma (Rb) protein, as a main tumor suppressor, controls cellular responses to potentially oncogenic stimulation. Rb phosphorylation could disrupt E2F complex formation, resulting in diverse transcription factor dysfunction. In our study, we investigated how Rb is involved in controlling urinary bladder cancer progression. The results indicate that Rb expression is reduced in mice with urinary bladder tumor, and its suppression leads to urinary bladder cancer progression in vivo and in vitro...
February 22, 2017: International Journal of Oncology
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