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Naoki Ikari, Shota Aoyama, Akiyoshi Seshimo, Yuji Suehiro, Tomoko Motohashi, Shohei Mitani, Sawako Yoshina, Etsuko Tanji, Akiko Serizawa, Takuji Yamada, Kiyoaki Taniguchi, Masakazu Yamamoto, Toru Furukawa
Background and aim: Intramucosal gastric adenocarcinoma of the well-moderately differentiated type only exhibits lymph node metastasis in extremely rare cases. We encountered such case and investigated both the lymphangiogenic properties and somatic mutations in the cancer to understand the prometastatic features of early-stage gastric cancer. Methods: We quantitatively measured the density of lymphatic vessels and identified mutations in 412 cancer-associated genes through next-generation target resequencing of DNA extracted from tumor cells in a formalin-fixed and paraffin-embedded tissue...
February 13, 2018: Oncotarget
Albert Giralt, Pierre-Damien Denechaud, Isabel C Lopez-Mejia, Brigitte Delacuisine, Emilie Blanchet, Caroline Bonner, Francois Pattou, Jean-Sébastien Annicotte, Lluis Fajas
OBJECTIVE: Aberrant hepatic glucose production contributes to the development of hyperglycemia and is a hallmark of type 2 diabetes. In a recent study, we showed that the transcription factor E2F1, a component of the cell cycle machinery, contributes to hepatic steatosis through the transcriptional regulation of key lipogenic enzymes. Here, we investigate if E2F1 contributes to hyperglycemia by regulating hepatic gluconeogenesis. METHODS: We use different genetic models to investigate if E2F1 regulates gluconeogenesis in primary hepatocytes and in vivo...
February 26, 2018: Molecular Metabolism
Dongxia Fu, Yunna Zhang, Haibin Cui
Pituitary adenomas, arising from the pituitary gland cells, are one of the most frequent tumors found in the sella region. However, the molecular mechanisms involved in the carcinogenesis and progression of pituitary adenomas is still not understood in detail. Long noncoding RNA (lncRNA) colon cancer-associated transcript 2 (CCAT2), a newly identified lncRNA, has been reported to be abnormally expressed in some cancers. In the present study, we found that CCAT2 was significantly upregulated in pituitary adenomas tissues...
2018: American Journal of Cancer Research
Yi Zhou, Ran Wei, Liu Zhang, Yongjiang Chen, Suying Lu, Chen Liang, Yujiao Wang, Lirong Xiao, Junjun Zhang, Rod Bremner, Danian Chen
Retinoblastoma tumor suppressor (Rb) promotes cell cycle exit, survival, differentiation, and tumor suppression in the retina. Here, we show it is also essential for vascularization and lamination. Despite minimal effects on Hif1a target expression, intraretinal vascular plexi did not form in the Rb-/- murine retina. Deleting adenovirus E2 promoter binding factor 3 (E2f3), which rescues starburst amacrine cell differentiation, or E2f2, had no effect, but deleting E2f1, which promotes neuronal cell cycle exit and survival, restored retinal vasculature...
March 6, 2018: Cell Death & Disease
Marianna Szemes, Alexander Greenhough, Zsombor Melegh, Sally Malik, Aysen Yuksel, Daniel Catchpoole, Kelli Gallacher, Madhu Kollareddy, Ji Hyun Park, Karim Malik
Neuroblastoma is one of the commonest and deadliest solid tumours of childhood, and is thought to result from disrupted differentiation of the developing sympathoadrenergic lineage of the neural crest. Neuroblastoma exhibits intra- and intertumoural heterogeneity, with high risk tumours characterised by poor differentiation, which can be attributable to MYCN-mediated repression of genes involved in neuronal differentiation. MYCN is known to co-operate with oncogenic signalling pathways such as Alk, Akt and MEK/ERK signalling, and, together with c-MYC has been shown to be activated by Wnt signalling in various tissues...
March 2, 2018: Neoplasia: An International Journal for Oncology Research
Hyun-Kyung Kim, Mi Ae Kang, Mi-Sook Kim, Young-Joo Shin, Sung-Gil Chi, Jae-Hoon Jeong
High mobility group box 2 (HMGB2) is an abundant, chromatin-associated, non-histone protein involved in transcription, chromatin remodeling, and recombination. Recently, the HMGB2 gene was found to be significantly downregulated during senescence and shown to regulate the expression of senescent-associated secretory proteins. Here, we demonstrate that HMGB2 transcription is repressed by p21 during radiation-induced senescence through the ATM-p53-p21 DNA damage signaling cascade. The loss of p21 abolished the downregulation of HMGB2 caused by ionizing radiation, and the conditional induction of p21 was sufficient to repress the transcription of HMGB2...
February 28, 2018: Molecules and Cells
Gemma B Danks, Pavla Navratilova, Boris Lenhard, Eric M Thompson
BACKGROUND: Development is largely driven by transitions between transcriptional programs. The initiation of transcription at appropriate sites in the genome is a key component of this and yet few rules governing selection are known. Here, we used cap analysis of gene expression (CAGE) to generate bp-resolution maps of transcription start sites (TSSs) across the genome of Oikopleura dioica, a member of the closest living relatives to vertebrates. RESULTS: Our TSS maps revealed promoter features in common with vertebrates, as well as striking differences, and uncovered key roles for core promoter elements in the regulation of development...
February 26, 2018: BMC Genomics
Jun Gu, Yu-Qi Fan, Hui-Li Zhang, Jian-An Pan, Jian-Ying Yu, Jun-Feng Zhang, Chang-Qian Wang
The clinical use of doxorubicin (DOX) is limited by cardiotoxicity, involving the dysregulation of autophagy and apoptosis in the myocardium, which were partly reversed by resveratrol (RSV) supplement. However, a definitive mechanisms accounting for DOX's cardiotoxicity and the protective role of RSV remain poorly defined. The aim of the present study was to clarify the specific role of E2F transcription factor 1(E2F1) in regulating autophagy and apoptosis in DOX-induced cardiotoxicity as well as the protective effects of RSV...
February 20, 2018: Biochemical Pharmacology
Ainhoa Iglesias-Ara, Nerea Osinalde, Ana M Zubiaga
The E2F transcription factors are key targets for the retinoblastoma (RB) tumor suppressor function. The active or inactive status of RB determines the degree by which E2F-dependent gene expression will occur in a given condition. Changes in transcriptional activity in response to extracellular or intracellular stimuli are frequently measured using genetic reporter assays. In particular, dual luciferase reporter assays are most recommended for this purpose because of their improved experimental accuracy. Here we illustrate the usefulness of the dual luciferase reporter assay to detect E2F-mediated transcriptional activity upon overexpression of E2F1 in cultured cells as readout for RB status and function...
2018: Methods in Molecular Biology
Xin Lai, Shailendra K Gupta, Ulf Schmitz, Stephan Marquardt, Susanne Knoll, Alf Spitschak, Olaf Wolkenhauer, Brigitte M Pützer, Julio Vera
High rates of lethal outcome in tumour metastasis are associated with the acquisition of invasiveness and chemoresistance. Several clinical studies indicate that E2F1 overexpression across high-grade tumours culminates in unfavourable prognosis and chemoresistance in patients. Thus, fine-tuning the expression of E2F1 could be a promising approach for treating patients showing chemoresistance. Methods: We integrated bioinformatics, structural and kinetic modelling, and experiments to study cooperative regulation of E2F1 by microRNA (miRNA) pairs in the context of anticancer chemotherapy resistance...
2018: Theranostics
Haizhou Liu, Hui Liu, Zhiyi Zhou, Robert A Parise, Edward Chu, John C Schmitz
BACKGROUND: 5-Fluorouracil (5-FU) remains the most widely used agent to treat colorectal cancer (CRC). However, its clinical efficacy is currently limited by the development of drug resistance. Traditional Chinese Herbal Medicine (TCM) has been shown to enhance the efficacy of standard anticancer agents. However, there are only a limited number of well-controlled preclinical and clinical studies documenting the potential benefit of TCM. Herein, we screened a series of TCM formulas in in vitro and in vivo animal models to identify biologically active formulas that were effective against CRC...
February 20, 2018: Cell Communication and Signaling: CCS
Hong-Jie Lu, Pei-Ying Jin, Yao Tang, Shao-Hua Fan, Zi-Feng Zhang, Fang Wang, Dong-Mei Wu, Jun Lu, Yuan-Lin Zheng
AIMS: Several microRNAs (miRs) are expressed aberrantly and associated with progression, tumorigenesis, and prognosis of haematological and solid tumors. The study aimed to identify the effects involved with microRNA-136 (miR-136) on the concurrent enhancement of proliferation, apoptosis and radiosensitivity of cervical carcinoma through the NF-κB signaling pathway by targeting E2F1. MAIN METHODS: Totally 338 patients with cervical carcinoma were recruited in this study...
February 13, 2018: Life Sciences
Michaela Angelika Ihle, Sebastian Huss, Wiebke Jeske, Wolfgang Hartmann, Sabine Merkelbach-Bruse, Hans-Ulrich Schildhaus, Reinhard Büttner, Harri Sihto, Kirsten Sundby Hall, Mikael Eriksson, Peter Reichardt, Heikki Joensuu, Eva Wardelmann
Despite of multitude investigations no reliable prognostic immunohistochemical biomarkers in GIST have been established so far with added value to predict the recurrence risk of high risk GIST besides mitotic count, primary location and size. In this study, we analyzed the prognostic relevance of eight cell cycle and apoptosis modulators and of TP53 mutations for prognosis in GIST with high risk of recurrence prior to adjuvant treatment with imatinib. In total, 400 patients with high risk for GIST recurrence were randomly assigned for adjuvant imatinib either for one or for three years following laparotomy...
2018: PloS One
Seong-Min Park, Eun-Young Choi, Dong-Hyuck Bae, Hyun Ahm Sohn, Seon-Young Kim, Youn-Jae Kim
BACKGROUND/AIMS: Recent studies have revealed that many long non-coding RNAs (lncRNAs) play oncogenic or tumor-suppressive roles in various cancers. Lung cancer is the leading cause of cancer-related death worldwide, and many lung cancer patients frequently relapse after surgery, even those in the early stages. However, the oncogenic or tumor-suppressive roles and clinical implications of lncRNAs in lung cancer have not been fully elucidated. METHODS: The association between an E2F-mediated cell proliferation enhancing lncRNA (EPEL) expression and lung cancer patient survival was accessed using public microarray data with clinical information...
February 9, 2018: Cellular Physiology and Biochemistry
Feng Su, Wang He, Changhao Chen, Mo Liu, Hongwei Liu, Feiyuan Xue, Junming Bi, Dawei Xu, Yue Zhao, Jian Huang, Tianxin Lin, Chun Jiang
Long non-coding RNAs (lncRNAs) have been identified as significant regulators in cancer progression. Positive feedback loops between lncRNAs and transcription factors have attracted increasing attention. Akt pathway plays a crucial role in bladder cancer growth and recurrence. In the present study, we demonstrate a novel regulatory pattern involving FOXD2-AS1, Akt, and E2F1. FOXD2-AS1 is highly expressed in bladder cancer and is associated with tumor stage, recurrence, and poor prognosis. Further experiments showed that FOXD2-AS1 promotes bladder cancer cell proliferation, migration, and invasion in vitro and in vivo...
February 14, 2018: Cell Death & Disease
Marianne Böni-Schnetzler, Stéphanie P Häuselmann, Elise Dalmas, Daniel T Meier, Constanze Thienel, Shuyang Traub, Friederike Schulze, Laura Steiger, Erez Dror, Praxedis Martin, Pedro L Herrera, Cem Gabay, Marc Y Donath
Interleukin-1 receptor antagonist (IL-1Ra) is elevated in the circulation during obesity and type 2 diabetes (T2D) but is decreased in islets from patients with T2D. The protective role of local IL-1Ra was investigated in pancreatic islet β cell (βIL-1Ra)-specific versus myeloid-cell (myeloIL-1Ra)-specific IL-1Ra knockout (KO) mice. Deletion of IL-1Ra in β cells, but not in myeloid cells, resulted in diminished islet IL-1Ra expression. Myeloid cells were not the main source of circulating IL-1Ra in obesity...
February 13, 2018: Cell Reports
Pei-Fang Xiao, Yan-Fang Tao, Shao-Yan Hu, Lan Cao, Jun Lu, Jian Wang, Xing Feng, Jian Pan, Yi-Huan Chai
Histone modification is dysregulated in various types of cancers, including hematological malignancies. However, the expression profile of histone-modifying enzymes in pediatric acute monoblastic leukemia (AML FAB M5) has not been investigated. In this study, we evaluated the mRNA expression profile of 85 genes that encode enzymes involved in histone-modification in 27 pediatric AML FAB M5 samples by using a novel real-time PCR array. We obtained a gene cluster consisting of a total of 28 genes (15 up-regulated genes and 13 down-regulated genes)...
March 1, 2017: Die Pharmazie
Ashok Daniel Prabakaran, Jimsheena Valiyakath Karakkat, Ranjit Vijayan, Jisha Chalissery, Marwa F Ibrahim, Suneesh Kaimala, Ernest A Adeghate, Ahmed Hasan Al-Marzouqi, Suraiya Anjum Ansari, Mensah-Brown Epk, Bright Starling Emerald
Although the existence of a close relationship between the early maternal developmental environment, fetal size at birth and the risk of developing disease in adulthood has been suggested, most studies, however, employed experimentally induced intrauterine growth restriction as model to link this with later adult disease. Since embryonic size variation occurs under normal growth and differentataion as well, elucidating the molecular mechanisms underlying these changes and their relevance to later adult disease risk becomes important...
January 30, 2018: Disease Models & Mechanisms
Fei Liu, Miao Dai, Qinyang Xu, Xiaolu Zhu, Yang Zhou, Shuheng Jiang, Yahui Wang, Zhihong Ai, Li Ma, Yanli Zhang, Lipeng Hu, Qin Yang, Jun Li, Shujie Zhao, Zhigang Zhang, Yincheng Teng
High-risk human papillomavirus oncoproteins E6 and E7 are the major etiological factors of cervical cancer but are insufficient for malignant transformation of cervical cancer. Dysregulated alternative splicing, mainly ascribed to aberrant splicing factor levels and activities, contributes to most cancer hallmarks. However, do E6 and E7 regulate the expression of splicing factors? Does alternative splicing acts as an "accomplice" of E6E7 to promote cervical cancer progression? Here, we identified that the splicing factor SRSF10, which promotes tumorigenesis of cervix, was upregulated by E6E7 via E2F1 transcriptional activation...
February 12, 2018: Oncogene
Natalia von Muhlinen, Izumi Horikawa, Fatima Alam, Kazunobu Isogaya, Delphine Lissa, Borek Vojtesek, David P Lane, Curtis C Harris
Cellular senescence is a hallmark of normal aging and aging-related syndromes, including the premature aging disorder Hutchinson-Gilford Progeria Syndrome (HGPS), a rare genetic disorder caused by a single mutation in the LMNA gene that results in the constitutive expression of a truncated splicing mutant of lamin A known as progerin. Progerin accumulation leads to increased cellular stresses including unrepaired DNA damage, activation of the p53 signaling pathway and accelerated senescence. We previously established that the p53 isoforms ∆133p53 and p53β regulate senescence in normal human cells...
February 12, 2018: Oncogene
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