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https://www.readbyqxmd.com/read/28634077/depdc1-promotes-cell-proliferation-and-tumor-growth-via-activation-of-e2f-signaling-in-prostate-cancer
#1
Lin Huang, Keng Chen, Zhao-Peng Cai, Fu-Chao Chen, Hui-Yong Shen, Wei-Hua Zhao, Song-Jie Yang, Xu-Biao Chen, Guo-Xue Tang, Xi Lin
DEP domain containing 1 (DEPDC1) is recently reported to be overexpressed in several types of human cancer; however the role of DEPDC1 in prostate cancer remains to be investigated. Herein, we identified that the DEPDC1 mRNA and protein expression levels were dramatically increased in prostate cancer tissues and cell lines. Overexpression of DEPDC1 promoted, but depletion of DEPDC1 inhibited cell proliferation by regulating the G1-S phase cell cycle transition. Importantly, we found that DEPDC1 was essential for the tumor growth and formation of bone metastases of prostate cancer cells in vivo...
June 17, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28620137/biological-specificity-of-cdk4-6-inhibitors-dose-response-relationship-in-vivo-signaling-and-composite-response-signature
#2
Erik S Knudsen, Jack Hutcheson, Paris Vail, Agnieszka K Witkiewicz
Recently developed potent and selective CDK4/6 inhibitors fall into two classes based on structure and toxicity profiles in clinical studies. One class, exemplified by palbociclib and ribociclib, exhibits neutropenia as a dose-limiting toxicity and requires discontinuous dosing. In contrast, the structurally distinct CDK4/6 inhibitor abemaciclib is dosed continuously, and has diarrhea and fatigue as dose-limiting toxicities. In preclinical models, palbociclib has been extensively studied and induces cell cycle inhibition in an RB-dependent manner...
June 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28614707/linker-histone-h1-2-directs-genome-wide-chromatin-association-of-the-retinoblastoma-tumor-suppressor-protein-and-facilitates-its-function
#3
Shonagh Munro, Edward S Hookway, Melanie Floderer, Simon M Carr, Rebecca Konietzny, Benedikt M Kessler, Udo Oppermann, Nicholas B La Thangue
The retinoblastoma tumor suppressor protein pRb is a master regulator of cellular proliferation, principally through interaction with E2F and regulation of E2F target genes. Here, we describe the H1.2 linker histone as a major pRb interaction partner. We establish that H1.2 and pRb are found in a chromatin-bound complex on diverse E2F target genes. Interrogating the global influence of H1.2 on the genome-wide distribution of pRb indicated that the E2F target genes affected by H1.2 are functionally linked to cell-cycle control, consistent with the ability of H1...
June 13, 2017: Cell Reports
https://www.readbyqxmd.com/read/28612064/e2f-site-in-the-essential-promoter-region-does-not-confer-s-phase-specific-transcription-of-the-abcc10-gene-in-human-prostate-cancer-cells
#4
Magdalena Dabrowska, Francis M Sirotnak
ABCC10 (MRP7) plays a role in cellular detoxification and resistance to anticancer drugs. Since ABCC10 gene transcription in human prostate cancer CWR22Rv1 cells was found dependent on E2F binding sequence motif, ABCC10 expression in G1 and S phases of the cell cycle of CWR22Rv1 cells, was analyzed. The cells were synchronized in G1 phase by double thymidine block and in S phase by thymidine/mimosine double block. ABCC10 mRNA level was found to be similar in S phase-synchronized and asynchronous cell populations...
2017: Acta Biochimica Polonica
https://www.readbyqxmd.com/read/28610850/dietary-myo-inositol-deficiency-decreased-the-growth-performances-and-impaired-intestinal-physical-barrier-function-partly-relating-to-nrf2-jnk-e2f4-and-mlck-signaling-in-young-grass-carp-ctenopharyngodon-idella
#5
Shuang-An Li, Wei-Dan Jiang, Lin Feng, Yang Liu, Pei Wu, Jun Jiang, Sheng-Yao Kuang, Ling Tang, Wu-Neng Tang, Yong-An Zhang, Xiao-Qiu Zhou
In this study, we investigated the effects of dietary myo-inositol on the growth and intestinal physical barrier functions of young grass carp (Ctenopharyngodon idella). A total of 540 young grass carp (221.83 ± 0.84 g) were fed six diets containing graded levels of myo-inositol (27.0, 137.9, 286.8, 438.6, 587.7 and 737.3 mg/kg) for 10 weeks. After the growth trial, fish were challenged with Aeromonas hydrophila for 14 days. The results indicated that compared with optimal myo-inositol levels, myo-inositol deficiency (27...
June 10, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28607595/e2f8-is-a-potential-therapeutic-target-for-hepatocellular-carcinoma
#6
REVIEW
Yi Lv, Jia Xiao, Jing Liu, Feiyue Xing
E2F transcriptional factors are widely expressed in a number of tissues and organs, possessing many regulatory functions related to cellular proliferation, differentiation, DNA repair, cell-cycle and cell apoptosis. E2F8 is a recently identified member of the E2F family with a duplicated DNA-binding domain feature discriminated from E2F1-6, controlling gene expression in a dimerization partner-independent manner. It is indispensable for angiogenesis, lymphangiogenesis and embryonic development. Although E2F8 and E2F7 perform complementary and overlapping functions in many cell metabolisms, E2F8, but not E2F7, overexpresses remarkably in hepatocellular carcinoma (HCC) to facilitate the HCC occurrence and development via activating a E2F1/ Cyclin D1 signaling pathway to regulate the G1- to S-phase transition of cell cycle progression or transcriptionally suppressing CDK1 to induce hepatocyte polyploidization...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28600888/homeostatic-control-of-start-through-negative-feedback-between-cln3-cdk1-and-rim15-greatwall-kinase-in-budding-yeast
#7
Nicolas Talarek, Elisabeth Gueydon, Etienne Schwob
How cells coordinate growth and division is key for size homeostasis. Phosphorylation by G1-CDK of Whi5/Rb inhibitors of SBF/E2F transcription factors triggers irreversible S-phase entry in yeast and metazoans, but why this occurs at a given cell size is not fully understood. We show that the yeast Rim15-Igo1,2 pathway, orthologous to Gwl-Arpp19/ENSA, is up-regulated in early G1 and helps promoting START by preventing PP2ACdc55 to dephosphorylate Whi5. RIM15 overexpression lowers cell size while IGO1,2 deletion delays START in cells with low CDK activity...
June 10, 2017: ELife
https://www.readbyqxmd.com/read/28599485/mirna-34a-enhances-the-sensitivity-of-gastric-cancer-cells-to-treatment-with-paclitaxel-by-targeting-e2f5
#8
Lina Li, Cuiling Wu, Yue Zhao
Gastric cancer (GC) is one of the most common types of malignant cancer worldwide, however improvements are required to the current therapies for GC. Although paclitaxel is one of the most promising chemotherapeutic agents in clinical use for GC, the resistance to paclitaxel that develops during treatment is a major obstacle to further treatments of GC. The present study reports that micro (mi) RNA-34a, a tumor suppressor in various types of cancer, may be an important regulator of chemoresistance in GC, as miRNA-34a mimics and inhibitors, enhance and inhibit the chemotherapeutic efficacy of paclitaxel, respectively...
June 2017: Oncology Letters
https://www.readbyqxmd.com/read/28596493/upregulation-of-long-noncoding-rna-hoxa-as3-promotes-tumor-progression-and-predicts-poor-prognosis-in-glioma
#9
Fan Wu, Chuanbao Zhang, Jinquan Cai, Fan Yang, Tingyu Liang, Xiaoyan Yan, Haoyuan Wang, Wen Wang, Jing Chen, Tao Jiang
Long noncoding RNAs (lncRNAs) have recently emerged as new potentially promising therapeutic targets in many cancers. However, their prognostic value and biological functions associated with glioma remain to be elucidated. Here, High-throughput RNAseq was performed to detect the expression profiles of lncRNAs in 325 human glioma tissues. It was shown that a novel lncRNA HOXA-AS3 was one of the most significantly upregulated lncRNAs in glioma tissues. Quantitative PCR further verified the increased expression of HOXA-AS3 in patient samples and glioma cell lines...
May 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28594957/distinctive-features-and-differential-regulation-of-the-drts-genes-of-arabidopsis-thaliana
#10
Antonio Maniga, Stefania Ghisaura, Lara Perrotta, Maria Giovanna Marche, Rino Cella, Diego Albani
In plants and protists, dihydrofolate reductase (DHFR) and thymidylate synthase (TS) are part of a bifunctional enzyme (DRTS) that allows efficient recycling of the dihydrofolate resulting from TS activity. Arabidopsis thaliana possesses three DRTS genes, called AtDRTS1, AtDRTS2 and AtDRTS3, that are located downstream of three members of the sec14-like SFH gene family. In this study, a characterization of the AtDRTS genes identified alternatively spliced transcripts coding for AtDRTS isoforms which may account for monofunctional DHFR enzymes supporting pathways unrelated to DNA synthesis...
2017: PloS One
https://www.readbyqxmd.com/read/28572744/berberine-regulates-the-protein-expression-of-multiple-tumorigenesis-related-genes-in-hepatocellular-carcinoma-cell-lines
#11
Tung-Yueh Chuang, Hsiao-Li Wu, Jie Min, Michael Diamond, Ricardo Azziz, Yen-Hao Chen
BACKGROUND: Hepatocellular carcinoma (HCC) is the seventh most common malignancy and the third leading cause of cancer-related death worldwide with an extremely grim prognosis. Berberine (BBR) has been found to inhibit proliferation of human HCC cells, although the underlying mechanism(s) are unclear. METHODS: Protein expression was detected by Western blots. Cell viability was determined by using the CellTiter Assay kit. RESULTS: We confirm that BBR treatment inhibits HepG2, Hep3B, and SNU-182 cell viability, and suggest that it regulates this proliferation via the modulation of multiple tumorigenesis-related genes protein expression...
2017: Cancer Cell International
https://www.readbyqxmd.com/read/28572168/preclinical-efficacy-and-molecular-mechanism-of-targeting-cdk7-dependent-transcriptional-addiction-in-ovarian-cancer
#12
Zhenfeng Zhang, Huixin Peng, Xiaojie Wang, Xia Yin, Pengfei Ma, Ying Jing, Mei-Chun Cai, Jin Liu, Meiying Zhang, Shengzhe Zhang, Kaixuan Shi, Wei-Qiang Gao, Wen Di, Guanglei Zhuang
Ovarian cancer remains a significant cause of gynecological cancer mortality and novel therapeutic strategies are urgently needed in clinic as new treatment options. We previously showed that BET bromodomain inhibitors displayed promising efficacy for the treatment of epithelial ovarian cancer by downregulating pivot transcription factors. However, the potential anti-tumor activities and molecular mechanisms of other epigenetic or transcriptional therapies have not been systematically determined. Here, by performing an unbiased high-throughput drug screen to identify candidate compounds with antineoplastic effects, we identified THZ1, a recently developed covalent CDK7 inhibitor, as a new transcription-targeting compound that exerted broad cytotoxicity against ovarian tumors...
June 1, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28570681/activated-e2f-activity-induces-cell-death-in-papillary-thyroid-carcinoma-k1-cells-with-enhanced-wnt-signaling
#13
Dong Yang, Chuanjiang Wang, Yingwei Luo, Xuan Li, Qingbin Song, Jian Zhang, Shijie Xin
Disruption of Wnt signaling often happens in tumorigenesis, but whether Wnt signaling affects the early stages of thyroid tumor, such as papillary thyroid carcinoma, is still a question, especially in the papillary thyroid carcinoma without genomic RET/PTC mutation. In this study, we demonstrated the important function of Wnt signaling in papillary thyroid carcinoma K1 cells, which have no RET/PTC mutation. We found that K1 cells have enhanced Wnt signaling in comparison to normal thyroid cells. We further demonstrated that K1 cells require the enhanced Wnt signaling for growth and survival...
2017: PloS One
https://www.readbyqxmd.com/read/28559983/feedback-between-e2f1-and-cip2a-regulated-by-human-papillomavirus-e7-in-cervical-cancer-implications-for-prognosis
#14
Xiao Wang, Peng Gao, Meng Wang, Jing Liu, Jiaxiang Lin, Shule Zhang, Yiwei Zhao, Jingwen Zhang, Wei Pan, Zeyu Sun, Feifei Sun, Weiming Zhao, Chenghao Guo, Qingwei Wang
Previously, we found that cancerous inhibitor of protein phosphatase 2A (CIP2A) plays a key role in the malignant transformation of cervical cancer. Here, we further explore whether and how CIP2A is regulated by human papillomavirus E7 (HPV E7) and the prognostic value of CIP2A in cervical cancer. We demonstrated a positive feedback loop between the E2F transcription factor 1 (E2F1) and CIP2A at the transcription level in HeLa and SiHa cells by real-time PCR and western blot analysis. The feedback, regulated by HPV E7, was further confirmed by their sub-cellular co-expression seen on immunofluorescence and immunohistochemistry staining in vitro and in vivo...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28558060/genomic-structure-expression-pattern-and-functional-characterization-of-transcription-factor-e2f-2-from-black-tiger-shrimp-penaeus-monodon
#15
Bobo Xie, Pengfei Wang, Chao Zhao, Lihua Qiu
Transcription factor E2F-2 is a regulator of cell cycle. Researchers identified E2F-2 genes from yeasts to humans, but few reports investigated E2F-2 gene from black tiger shrimp. In the present study, we cloned E2F-2 gene from black tiger shrimp (Penaeus monodon). Full-length PmE2F-2 complementary DNA sequence measures 3,189 bp with an open reading frame of 1,371 bp. Complete PmE2F-2 genomic sequence (17,305 bp) of P. monodon contains nine exons, which are separated by eight introns. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis indicated that PmE2F-2 is highly expressed in hepatopancreas and ovaries of P...
2017: PloS One
https://www.readbyqxmd.com/read/28555064/induction-of-p53-independent-apoptosis-and-g1-cell-cycle-arrest-by-fucoidan-in-hct116-human-colorectal-carcinoma-cells
#16
Hye Young Park, Shin-Hyung Park, Jin-Woo Jeong, Dahye Yoon, Min Ho Han, Dae-Sung Lee, Grace Choi, Mi-Jin Yim, Jeong Min Lee, Do-Hyung Kim, Gi-Young Kim, Il-Whan Choi, Suhkmann Kim, Heui-Soo Kim, Hee-Jae Cha, Yung Hyun Choi
It is well known that fucoidan, a natural sulfated polysaccharide present in various brown algae, mediates anticancer effects through the induction of cell cycle arrest and apoptosis. Nevertheless, the role of tumor suppressor p53 in the mechanism action of fucoidan remains unclear. Here, we investigated the anticancer effect of fucoidan on two p53 isogenic HCT116 (p53+/+ and p53-/-) cell lines. Our results showed that inhibition of cell viability, induction of apoptosis and DNA damage by treatment with fucoidan were similar in two cell lines...
May 30, 2017: Marine Drugs
https://www.readbyqxmd.com/read/28550162/rb-family-proteins-enforce-the-homeostasis-of-quiescent-hematopoietic-stem-cells-by-repressing-socs3-expression
#17
Eunsun Kim, Ying Cheng, Elisabeth Bolton-Gillespie, Xiongwei Cai, Connie Ma, Amy Tarangelo, Linh Le, Madhumita Jambhekar, Pichai Raman, Katharina E Hayer, Gerald Wertheim, Nancy A Speck, Wei Tong, Patrick Viatour
Prolonged exit from quiescence by hematopoietic stem cells (HSCs) progressively impairs their homeostasis in the bone marrow through an unidentified mechanism. We show that Rb proteins, which are major enforcers of quiescence, maintain HSC homeostasis by positively regulating thrombopoietin (Tpo)-mediated Jak2 signaling. Rb family protein inactivation triggers the progressive E2f-mediated transactivation of Socs3, a potent inhibitor of Jak2 signaling, in cycling HSCs. Aberrant activation of Socs3 impairs Tpo signaling and leads to impaired HSC homeostasis...
May 26, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28548702/p16-loss-and-e2f-cell-cycle-deregulation-in-infant-posterior-fossa-ependymoma
#18
Seth C Lummus, Andrew M Donson, Katherine Gowan, Kenneth L Jones, Rajeev Vibhakar, Nicholas K Foreman, B K Kleinschmidt-DeMasters
BACKGROUND: Posterior fossa (PF) ependymomas (EPNs) in infants less than 1 year of age (iEPN-PF) have a poorer clinical outcome than EPNs in older children. While radiation therapy is the standard of care for the latter, it is withheld in infants to avoid neurotoxicity to immature brain. It is unknown whether the adverse outcome in iEPN-PFs is due to treatment differences or aggressive biology. We examined this question using molecular profiling. METHODS: Six anaplastic iEPN-PFs were subjected to transcriptomic analysis and FISH for p16 loss and gains of 1q, and compared with anaplastic PF EPNs from older children...
May 26, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28542143/dna-damage-and-s-phase-dependent-e2f1-stabilization-requires-the-ciap1-e3-ubiquitin-ligase-and-is-associated-with-k63-poly-ubiquitination-on-lysine-161-164-residues
#19
Valérie Glorian, Jennifer Allègre, Jean Berthelet, Baptiste Dumetier, Pierre-Marie Boutanquoi, Nathalie Droin, Cémile Kayaci, Jessy Cartier, Simon Gemble, Guillaume Marcion, Daniel Gonzalez, Romain Boidot, Carmen Garrido, Olivier Michaud, Eric Solary, Laurence Dubrez
The E2F transcription factor 1 is subtly regulated along the cell cycle progression and in response to DNA damage by post-translational modifications. Here, we demonstrated that the E3-ubiquitin ligase cellular inhibitor of apoptosis 1 (cIAP1) increases E2F1 K63-poly-ubiquitination on the lysine residue 161/164 cluster, which is associated with the transcriptional factor stability and activity. Mutation of these lysine residues completely abrogates the binding of E2F1 to CCNE, TP73 and APAF1 promoters, thus inhibiting transcriptional activation of these genes and E2F1-mediated cell proliferation control...
May 25, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28526299/mir-200a-regulates-cdk4-6-inhibitor-effect-by-targeting-cdk6-in-metastatic-melanoma
#20
Matias A Bustos, Shigeshi Ono, Diego M Marzese, Takashi Oyama, Yuuki Iida, Garrett Cheung, Nellie Nelson, Sandy C Hsu, Qiang Yu, Dave S B Hoon
Cyclin-dependent kinase (CDK) 4 and 6 pathway is frequently dysregulated in cutaneous melanoma. Recently, CDK4/6 inhibitors have shown promising clinical activity against several cancer types, including melanoma. Here, we demonstrate that miR-200a decreases CDK6 expression and thus reduces the response of CDK4/6 inhibitor in highly proliferative metastatic melanoma. Down-regulation of miR-200a expression in melanoma cells is associated with disease progression and a higher number of lymph node metastases. Furthermore, miR-200a expression is epigenetically modulated by both DNA methylation at the promoter region and chromatin accessibility of an upstream genomic region with enhancer activity...
May 16, 2017: Journal of Investigative Dermatology
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