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https://www.readbyqxmd.com/read/28526299/mir-200a-regulates-cdk4-6-inhibitor-effect-by-targeting-cdk6-in-metastatic-melanoma
#1
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
https://www.readbyqxmd.com/read/28522584/cooperative-targets-of-combined-mtor-hdac-inhibition-promote-myc-degradation
#2
John K Simmons, Aleksandra M Michalowski, Benjamin J Gamache, Wendy DuBois, Jyoti Patel, Ke Zhang, Joy Gary, Shuling Zhang, Snehal Gaikwad, Daniel Connors, Nicholas Watson, Elena Leon, Jin-Qiu Chen, W Michael Kuehl, Maxwell P Lee, Adriana Zingone, Ola Landgren, Peter Ordentlich, Jing Huang, Beverly A Mock
Cancer treatments often require combinations of molecularly targeted agents to be effective. mTORi (rapamycin) and HDACi (MS-275/entinostat) inhibitors have been shown to be effective in limiting tumor growth, and here we define part of the cooperative action of this drug combination. More than 60 human cancer cell lines responded synergistically (CI<1) when treated with this drug combination compared to single agents.  In addition, a breast cancer patient-derived xenograft, and a BCL-XL plasmacytoma mouse model both showed enhanced responses to the combination compared to single agents...
May 18, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28522430/the-drosophila-lin54-homolog-mip120-controls-two-aspects-of-oogenesis
#3
Mei-Hsin Cheng, Laura Andrejka, Paul J Vorster, Albert Hinman, Joseph S Lipsick
The conserved multi-protein MuvB core associates with the Myb oncoproteins and with the RB-E2F-DP tumor suppressor proteins in complexes that regulate cell proliferation, differentiation, and apoptosis. Drosophila Mip120, a homolog of LIN54, is a sequence-specific DNA-binding protein within the MuvB core. A mutant of Drosophila mip120 was previously shown to cause female and male sterility. We now show that Mip120 regulates two different aspects of oogenesis. First, in the absence of the Mip120 protein, egg chambers arrest during the transition from stage 7 to 8 with a failure of the normal program of chromosomal dynamics in the ovarian nurse cells...
May 18, 2017: Biology Open
https://www.readbyqxmd.com/read/28521474/an-%C3%AE-3-fatty-acid-desaturase-expressing-gene-attenuates-prostate-cancer-proliferation-by-cell-cycle-regulation
#4
Jinshun Pan, Sujin Zhou, Rong Xiang, Zhenggang Zhao, Shanshan Liu, Ning Ding, Sijia Gong, Yan Lin, Xiaoxi Li, Xiaoming Bai, Fanghong Li, Allan Z Zhao
Previous studies have reported that Ω-6 and Ω-3 fatty acids have opposing effects on cancer development. Consuming high levels of long-chain Ω-3 polyunsaturated fatty acids (PUFAs) has been shown to reduce prostate cancer risk and increase chemotherapy sensitivity. The sdd17 gene encodes an Ω-3 fatty acid desaturase, which converts arachidonic acid into eicosapentaenoic acid (EPA). However, little is known regarding the function of the sdd17 gene in tumor cells in vitro. In the present study, prostate cancer cells were infected with the msdd17 gene, which allowed the endogenous production of Ω-3 PUFAs...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28511966/identification-of-potential-target-genes-and-related-regulatory-transcription-factors-in-spontaneous-hairline-fracture-induced-by-hypervitaminosis-a
#5
Chuangang Peng, Qi Yang, Bo Wei, Yong Liu, Yuxiang Li, Dawei Gu, Guochao Yin, Bo Wang, Dehui Xu, Xuebing Zhang, Daliang Kong
BACKGROUND: The aim was to research the molecular changes of bone cells induced by excessive dose of vitamin A, and analyze molecular mechanism underlying spontaneous fracture. METHODS: The gene expression profile of GSE29859, including 4 cortical bone marrow samples with excessive doses of Vitamin A and 4 control cortical bone marrow samples, was obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DGEs) between cortical bone marrow samples and control samples were screened out and pathway enrichment analysis was undertaken...
May 2, 2017: Injury
https://www.readbyqxmd.com/read/28500630/e2f-is-involved-in-radioresistance-of-carbon-ion-induced-apoptosis-via-bax-caspase-3-signal-pathway-in-human-hepatoma-cell
#6
Xie Yi, S I Jing, Wang Yu-Pei, L I Hong-Yan, D I Cui-Xia, Yan Jun-Fang, Y E Yan-Cheng, Zhang Yan-Shan, Zhang Hong
Deletion of p53, most common genetic alteration, is observed in human tumors and reported to lead to improve in cell radioresistance. Heavy-ion irradiation (IR) could induce p53-/- cancer cells apoptosis. However, little is known regarding the molecular mechanism in this type of cell apoptosis. The present studies have focused on mechanisms state of signaling pathways as an activator of the cell fate decisions induced by heavy ion IR without p53. Carbon ion IR could induce up-regulation of E2F1 expression in cancer cells...
May 13, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28493844/mirnas-and-e2f3-a-complex-network-of-reciprocal-regulations-in-human-cancers
#7
REVIEW
Yanping Gao, Bing Feng, Lu Lu, Siqi Han, Xiaoyuan Chu, Longbang Chen, Rui Wang
E2F transcription factor 3 (E2F3) is oncogenic in tumorigenesis. Alterations in E2F3 functions correspond with poor prognosis in various cancers, underscoring their status for the clinical cancer phenotype. Latest reports discovered intricate networks between microRNAs (miRNAs) and E2F3 in regulating the balance of these events, including proliferation, apoptosis, metastasis, as well as drug resistance. miRNAs are non-coding small RNAs which negatively regulate gene expressions post-transcriptionally mainly through 3'-UTR binding of target mRNAs...
April 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28490465/dual-inhibition-of-ezh2-and-ezh1-sensitizes-prc2-dependent-tumors-to-proteasome-inhibition
#8
Ola Rizq, Naoya Mimura, Motohiko Oshima, Atsunori Saraya, Shuhei Koide, Yuko Kato, Kazumasa Aoyama, Yaeko Nakajima-Takagi, Changshan Wang, Tetsuhiro Chiba, Anqi Ma, Jian Jin, Tohru Iseki, Chiaki Nakaseko, Atsushi Iwama
<br /> <p>EZH2 and EZH1, the catalytic components of polycomb repressive complex 2 (PRC2), trigger trimethylation of H3K27 (H3K27me3) to repress the transcription of target genes and are implicated in the pathogenesis of various cancers including multiple myeloma (MM) and prostate cancer. Here, we investigated the preclinical effects of UNC1999, a dual inhibitor of EZH2 and EZH1, in combination with proteasome inhibitors on MM and prostate cancer.</p> <br /><br />Experimental Design: <br /> <p>In vitro and in vivo efficacy of UNC1999 and the combination with proteasome inhibitors was evaluated in MM cell lines, primary patient cells and in a xenograft model...
May 10, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28488543/the-transcription-factor-foxa1-induces-epithelial-ovarian-cancer-tumorigenesis-and-progression
#9
Li-Li Wang, Yin-Ling Xiu, Xi Chen, Kai-Xuan Sun, Shuo Chen, Dan-Dan Wu, Bo-Liang Liu, Yang Zhao
FOXA1 (forkhead box A1), a member of the FOXA transcription factor superfamily, plays an important role in tumor occurrence and development. However, the relationship between FOXA1 and ovarian cancer has not been reported. We examined normal ovarian tissue and ovarian cancer tissue and found increased FOXA1 expression in the cancer tissue. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and flow cytometry assays demonstrated that transfection with small interfering RNA to silence FOXA1 (si-FOXA1) in ovarian cancer cell lines decreased cell proliferation and induced apoptosis and S-phase arrest...
May 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28484242/regulation-of-chk1-by-mtor-contributes-to-the-evasion-of-dna-damage-barrier-of-cancer-cells
#10
Xinhui Zhou, Weijin Liu, Xing Hu, Adrienne Dorrance, Ramiro Garzon, Peter J Houghton, Changxian Shen
Oncogenic transformation leads to dysregulated cell proliferation, nutrient deficiency, and hypoxia resulting in metabolic stress and increased DNA damage. In normal cells, such metabolic stress leads to inhibition of signaling through the mammalian Target of Rapamycin Complex 1 (mTORC1), reduction of protein translation, cell cycle arrest, and conservation of energy. In contrast, negative regulation of mTORC1 signaling by DNA damage is abrogated in many cancer cells, thus mTORC1 signaling remains active under microenvironmental conditions that potentially promote endogenous DNA damage...
May 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28484034/modeling-the-response-of-a-tumor-suppressive-network-to-mitogenic-and-oncogenic-signals
#11
Xinyu Tian, Bo Huang, Xiao-Peng Zhang, Mingyang Lu, Feng Liu, José N Onuchic, Wei Wang
Intrinsic tumor-suppressive mechanisms protect normal cells against aberrant proliferation. Although cellular signaling pathways engaged in tumor repression have been largely identified, how they are orchestrated to fulfill their function still remains elusive. Here, we built a tumor-suppressive network model composed of three modules responsible for the regulation of cell proliferation, activation of p53, and induction of apoptosis. Numerical simulations show a rich repertoire of network dynamics when normal cells are subject to serum stimulation and adenovirus E1A overexpression...
May 8, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28476582/enhanced-karyopherin-%C3%AE-2-expression-is-associated-with-carcinogenesis-in-patients-with-intraductal-papillary-mucinous-neoplasms
#12
Norio Kubo, Kenichiro Araki, Bolag Altan, Kouki Hoshino, Norihiro Ishii, Mariko Tsukagoshi, Takamichi Igarashi, Akira Watanabe, Toshihide Kato, Keitaro Hirai, Takehiko Yokobori, Fumiyoshi Saito, Hideki Suzuki, Hiroyuki Kuwano, Ken Shirabe
BACKGROUND/OBJECTIVES: Intraductal papillary mucinous neoplasms (IPMN) can become malignant. Karyopherin-α2 (KPNA2) plays a central role in nucleocytoplasmic transport and is associated with various types of cancer. The current study examined pancreatic KPNA2 expression in cancer patients and evaluated its association with clinicopathological factors, cancer cell proliferation. METHODS: KPNA2 expression was investigated by immunohistochemistry in 40 surgically resected IPMN samples and its association with clinicopathological factors and Ki-67 expression were examined...
April 23, 2017: Pancreatology: Official Journal of the International Association of Pancreatology (IAP) ... [et Al.]
https://www.readbyqxmd.com/read/28475649/blocking-smad2-signalling-with-loganin-attenuates-sw10-cell-cycle-arrest-induced-by-tnf-%C3%AE
#13
Gao Chao, Xiaoning Tian, Wentao Zhang, Xuehai Ou, Fei Cong, Tao Song
The activity of Schwann cells (SWCs) is very important in trauma-induced nerve repair, and tumour necrosis factor-α (TNF-α) produced during tissue injury inhibits the viability of SWCs, which delays the repair of peripheral nerves. Loganin is an iridoid glycoside that has been shown to alleviate a variety of cytotoxic effects. In the current study, we evaluated the potential efficacy and the mechanism of action of loganin in TNF-α-induced cytotoxicity in SW10 cells. The experimental results indicated that loganin blocked TNF-α-mediated Smad2 activation, downregulated the expression of the G1 phase cell cycle inhibitor p15IN4KB, and upregulated the expression of the G1 phase cell cycle activator cyclin D1-CDK4/6, which upregulated E2F-1-dependent survivin expression and relieved TNF-α-induced apoptosis in SW10 cells...
2017: PloS One
https://www.readbyqxmd.com/read/28474358/e2f1interactive-with-brca1-pathway-induces-hcc-two-different-small-molecule-metabolism-or-cell-cycle-regulation-via-mitochondrion-or-cd4-t-to-cytosol
#14
Qingchun Chen, Lin Wang, Minghu Jiang, Juxiang Huang, Zhenfu Jiang, Haitao Feng, Zhili Ji
Breast cancer 1 (BRCA1) and E2F transcription factor 1 (E2F1) are related to metabolism and cell cycle regulation. However, the corresponding mechanism is not clear in HCC. High BRCA1 direct pathway was constructed with 11 molecules from E2F1 feedback-interactive network in HCC by GRNInfer based on 39 Pearson mutual positive corelation CC >0.25 molecules with E2F1. Integration of GRNInfer with GO, KEGG, BioCarta, GNF_U133A, UNIGENE_EST, Disease, GenMAPP databases by DAVID and MAS 3.0, E2F1 feedback-interactive BRCA1 indirect mitochondrion to cytosol pathway was identified as upstream LAPTM4B activation, feedback UNG, downstream BCAT1-HIST1H2AD-TK1 reflecting protein and DNA binding with enrichment of small molecule metabolism; The corresponding BRCA1 indirect membrane to cytosol pathway as upstream CCNB2-NUSAP1 activation, feedback TTK-HIST1H2BJ-CENPF, downstream MCM4-TK1 reflecting ATP and microtubule binding with enrichment of CD4+T-related cell cycle regulation in HCC...
May 5, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28463795/cisatracurium-induced-proliferation-impairment-and-death-of-colorectal-cancer-cells-hct116-is-mediated-by-p53-dependent-intrinsic-apoptotic-pathway-in-vitro
#15
Iddrisu Baba Yabasin, ZhiLi Lu, Jia-Chuan Yu, Qingping Wen
Activation of oncogenes and suppression of repressor genes are believed to play crucial roles in the pathogenesis of human colorectal carcinoma. Cisatracurium, a nondepolarizing neuromuscular blocking agent, has been reported to inhibit cell proliferation while promoting apoptosis. However, the underlining mechanism, of these growth setbacks are not well understood. We assessed the growth of human colorectal carcinoma (HCT116) and its cell cycle distribution upon cisatracurium exposure. Significant cell growth inhibition and accumulation of cells in G1 phase of the cell cycle was observed in treated cells compared with untreated cells (control)...
April 29, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28448802/ddk-promotes-tumor-chemoresistance-and-survival-via-multiple-pathways
#16
Nanda Kumar Sasi, Arjun Bhutkar, Nathan J Lanning, Jeffrey P MacKeigan, Michael Weinreich
DBF4-dependent kinase (DDK) is a two-subunit kinase required for initiating DNA replication at individual origins and is composed of CDC7 kinase and its regulatory subunit DBF4. Both subunits are highly expressed in many diverse tumor cell lines and primary tumors, and this is correlated with poor prognosis. Inhibiting DDK causes apoptosis of tumor cells, but not normal cells, through a largely unknown mechanism. Firstly, to understand why DDK is often overexpressed in tumors, we identified gene expression signatures that correlate with DDK high- and DDK low-expressing lung adenocarcinomas...
May 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28439018/conservation-and-divergence-of-c-terminal-domain-structure-in-the-retinoblastoma-protein-family
#17
Tyler J Liban, Edgar M Medina, Sarvind Tripathi, Satyaki Sengupta, R William Henry, Nicolas E Buchler, Seth M Rubin
The retinoblastoma protein (Rb) and the homologous pocket proteins p107 and p130 negatively regulate cell proliferation by binding and inhibiting members of the E2F transcription factor family. The structural features that distinguish Rb from other pocket proteins have been unclear but are critical for understanding their functional diversity and determining why Rb has unique tumor suppressor activities. We describe here important differences in how the Rb and p107 C-terminal domains (CTDs) associate with the coiled-coil and marked-box domains (CMs) of E2Fs...
April 24, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28436337/molecular-cloning-expression-and-characterization-of-e2f-transcription-factor-4-from-antheraea-pernyi
#18
M N Abbas, S Kausar, Y-X Sun, Y Sun, L Wang, C Qian, G-Q Wei, B-J Zhu, C-L Liu
The E2F transcription factor family is distributed widely in eukaryotes and has been well studied among mammals. In the present study, the E2F transcription factor 4 (E2F4) gene was isolated from fat bodies of Antheraea pernyi and sequenced. E2F4 comprised a 795 bp open reading frame encoding a deduced amino acid sequence of 264 amino acid residues. The recombinant protein was expressed in Escherichia coli (Transetta DE3), and anti-E2F4 antibodies were prepared. The deduced amino acid sequence displayed significant homology to an E2F4-like protein from Bombyx mori L...
April 24, 2017: Bulletin of Entomological Research
https://www.readbyqxmd.com/read/28423601/a-novel-lncrna-gasl1-inhibits-cell-proliferation-and-restricts-e2f1-activity
#19
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
#20
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
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