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https://www.readbyqxmd.com/read/28214890/a-new-perspective-for-osteosarcoma-therapy-proteasome-inhibition-by-mln9708-2238-successfully-induces-apoptosis-and-cell-cycle-arrest-and-attenuates-the-invasion-ability-of-osteosarcoma-cells-in-vitro
#1
Renhao Liu, Chunjiang Fu, Jiabing Sun, Xvming Wang, Shuo Geng, Xiaoyu Wang, Jilong Zou, Zhenggang Bi, Chenglin Yang
BACKGROUND: The proteasome exists in all eukaryotic cells and provides the main route of intracellular proteins degradation involved in cell growth and apoptosis. Proteasome inhibition could block protein degradation pathways and disturb regulatory networks, possibly leading to profound effects on cell growth, particularly in cancer cells. A proteasome inhibitor with an appropriate toxicity index for malignant cells rather than normal cells would be an attractive anticancer therapy. METHODS: The human osteosarcoma (OS) cell lines MG-63 and Saos-2 and normal osteoblast cells were used to study the antitumour activity of the proteasome inhibitor MLN9708/2238...
January 27, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28211871/expression-level-is-a-key-determinant-of-e2f1-mediated-cell-fate
#2
Igor Shats, Michael Deng, Adam Davidovich, Carolyn Zhang, Jungeun S Kwon, Dinesh Manandhar, Raluca Gordân, Guang Yao, Lingchong You
The Rb/E2F network has a critical role in regulating cell cycle progression and cell fate decisions. It is dysfunctional in virtually all human cancers, because of genetic lesions that cause overexpression of activators, inactivation of repressors, or both. Paradoxically, the downstream target of this network, E2F1, is rarely strongly overexpressed in cancer. E2F1 can induce both proliferation and apoptosis but the factors governing these critical cell fate decisions remain unclear. Previous studies have focused on qualitative mechanisms such as differential cofactors, posttranslational modification or state of other signaling pathways as modifiers of the cell fate decisions downstream of E2F1 activation...
February 17, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28199407/keratin14-mrna-expression-in-human-pneumocytes-during-quiescence-repair-and-disease
#3
Marco Confalonieri, Emanuele Buratti, Gabriele Grassi, Rossana Bussani, Marco Chilosi, Rossella Farra, Michela Abrami, Cristiana Stuani, Francesco Salton, Miriam Ficial, Paola Confalonieri, Lorenzo Zandonà, Maurizio Romano
The lung alveoli slowly self-renew pneumocytes, but their facultative regeneration capacity is rapidly efficient after an injury, so fibrosis infrequently occurs. We recently observed Keratin 14 (KRT14) expression during diffuse alveolar damage (DAD), but not in controls. We wonder if KRT14 may be a marker of pneumocyte transition from quiescence to regeneration. Quantitative PCR and Western blot analyses highlighted the presence of KRT14 (mRNA and protein) only in human lung samples with DAD or interstitial lung disease (ILD)...
2017: PloS One
https://www.readbyqxmd.com/read/28197392/p38-mapk-differentially-controls-nk-activating-ligands-at-transcriptional-and-post-transcriptional-level-on-multiple-myeloma-cells
#4
Alessandra Soriani, Cristiana Borrelli, Biancamaria Ricci, Rosa Molfetta, Alessandra Zingoni, Cinzia Fionda, Silvia Carnevale, Maria Pia Abruzzese, Maria Teresa Petrucci, Maria Rosaria Ricciardi, Giuseppe La Regina, Erica Di Cesare, Patrizia Lavia, Romano Silvestri, Rossella Paolini, Marco Cippitelli, Angela Santoni
The mechanisms that regulate the expression of the NKG2D and DNAM-1 activating ligands are only partially known, but it is now widely established that their expression is finely regulated at transcriptional, post-transcriptional and post-translational level, and involve numerous stress pathways depending on the type of ligand, stressor, and cell context. We show that treatment of Multiple Myeloma (MM) cells with sub-lethal doses of Vincristine (VCR), an anticancer drug that inhibits the assembly of microtubules, stimulates the expression of NKG2D and DNAM-1 activating ligands, rendering these cells more susceptible to NK cell-mediated killing...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28184930/resveratrol-enhances-the-radiosensitivity-of-nasopharyngeal-carcinoma-cells-by-downregulating-e2f1
#5
Yuhui Tan, Xianli Wei, Wenyin Zhang, Xiaolan Wang, Kun Wang, Biaoyan Du, Jianyong Xiao
Identification of safe, effective radiosensitizing agents is urgently needed to improve the outcome of radiotherapy in nasopharyngeal cancer (NPC). In this study, we assessed the ability of the polyphenol resveratrol to act as a radiosensitizer in vitro and in vivo. CNE-1 cells were treated with 50 µM resveratrol for 24 h, then irradiated. E2F transcription factor 1 (E2F1) was stably knocked down and overexpressed using lentiviruses. A xenograft model of NPC was established in nude mice using CNE-1 cells...
March 2017: Oncology Reports
https://www.readbyqxmd.com/read/28176922/inhibition-of-skp2-sensitizes-lung-cancer-cells-to-paclitaxel
#6
Tonghai Huang, Lin Yang, Guangsuo Wang, Guanggui Ding, Bin Peng, Yuxin Wen, Zheng Wang
S-phase kinase-associated protein 2 (Skp2) is an E3 ubiquitin ligase and plays an important role in the control of cell cycle progression. Skp2 is upregulated in several cancers, including lung cancers, but the role of Skp2 in the tumorigenesis and anticancer drug resistance in human lung cancer remains to be determined. We report here that Skp2 positively regulated mitotic arrest deficient 2 (MAD2) expression and that inhibition of Skp2 sensitizes human lung cancer cells to paclitaxel. Knockdown of Skp2 by small interfering RNA (siRNA) decreased Mad2 messenger RNA (mRNA) and protein levels in A549 and NCI-H1975 cells, accompanied with upregulation of p27 but decrease of the phosphorylation of retinoblastoma (Rb)...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28174209/oncoprotein-cip2a-is-stabilized-via-interaction-with-tumor-suppressor-pp2a-b56
#7
Jiao Wang, Juha Okkeri, Karolina Pavic, Zhizhi Wang, Otto Kauko, Tuuli Halonen, Grzegorz Sarek, Päivi M Ojala, Zihe Rao, Wenqing Xu, Jukka Westermarck
Protein phosphatase 2A (PP2A) is a critical human tumor suppressor. Cancerous inhibitor of PP2A (CIP2A) supports the activity of several critical cancer drivers (Akt, MYC, E2F1) and promotes malignancy in most cancer types via PP2A inhibition. However, the 3D structure of CIP2A has not been solved, and it remains enigmatic how it interacts with PP2A. Here, we show by yeast two-hybrid assays, and subsequent validation experiments, that CIP2A forms homodimers. The homodimerization of CIP2A is confirmed by solving the crystal structure of an N-terminal CIP2A fragment (amino acids 1-560) at 3...
February 7, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28172637/p103-evaluation-of-efficacy-of-new-vectors-for-sirna-cyclin-d1-and-e2f1-delivery-in-control-of-cancer-progression-in-inflammatory-bowel-disease
#8
I Russo, S Bochicchio, O Piazza, A A Barba, G Lamberti, A Carrizzo, P Zeppa, C Vecchione, P Iovino, C Ciacci
No abstract text is available yet for this article.
February 1, 2017: Journal of Crohn's & Colitis
https://www.readbyqxmd.com/read/28146423/e2f-1-targets-mir-519d-to-regulate-the-expression-of-the-ras-homolog-gene-family-member-c
#9
Xiu-Bo Sang, Zhi-Hong Zong, Li-Li Wang, Dan-Dan Wu, Shuo Chen, Bo-Liang Liu, Yang Zhao
E2F1 (E2F transcription factor 1) can act as a tumor suppressor or oncogene. We report the molecular mechanism of E2F1 in ovarian carcinoma tumorigenesis and progression. E2F1 expression levels in ovarian carcinoma tissue were examined by immunohistochemistry. After E2F1 plasmid transfection and E2F1-microRNA-519d (miR-519d)/si-RhoC (Ras homolog gene family member C) co-transfection, ovarian cancer cell phenotypes and the related molecules were examined in vitro and in vivo. E2F1 was overexpressed in type I and type II ovarian carcinoma as compared to normal ovary tissues and normal fallopian tube tissues, respectively...
January 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28134624/dosage-dependent-copy-number-gains-in-e2f1-and-e2f3-drive-hepatocellular-carcinoma
#10
Lindsey N Kent, Sooin Bae, Shih-Yin Tsai, Xing Tang, Arunima Srivastava, Christopher Koivisto, Chelsea K Martin, Elisa Ridolfi, Grace C Miller, Sarah M Zorko, Emilia Plevris, Yannis Hadjiyannis, Miguel Perez, Eric Nolan, Raleigh Kladney, Bart Westendorp, Alain de Bruin, Soledad Fernandez, Thomas J Rosol, Kamal S Pohar, James M Pipas, Gustavo Leone
Disruption of the retinoblastoma (RB) tumor suppressor pathway, either through genetic mutation of upstream regulatory components or mutation of RB1 itself, is believed to be a required event in cancer. However, genetic alterations in the RB-regulated E2F family of transcription factors are infrequent, casting doubt on a direct role for E2Fs in driving cancer. In this work, a mutation analysis of human cancer revealed subtle but impactful copy number gains in E2F1 and E2F3 in hepatocellular carcinoma (HCC)...
January 30, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28132898/investigation-of-g-quadruplex-formation-in-the-fgfr2-promoter-region-and-its-transcriptional-regulation-by-liensinine
#11
Lulu Zhang, Wei Tan, Jiang Zhou, Ming Xu, Gu Yuan
BACKGROUND: Fibroblast growth factor receptor 2 (FGFR2) is overexpressed in breast cancer tissues and cells, and has been shown to be a susceptibility factor for breast cancer. In this study, we found that the G-rich sequences in the FGFR2 promoter region can form G-quadruplexes, which could be the target and inhibitor of the FGFR2 gene. METHODS: Initially, the formation of G-quadruplexes was confirmed by ESI-MS and CD, and DMS footprinting experiments gave the folding pattern of the G-quadruplexes...
January 27, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28125090/loss-of-gcn5-leads-to-increased-neuronal-apoptosis-by-upregulating-e2f1-and-egr-1-dependent-bh3-only-protein-bim
#12
Yanna Wu, Shanshan Ma, Yong Xia, Yangpeng Lu, Shiyin Xiao, Yali Cao, Sidian Zhuang, Xiangpeng Tan, Qiang Fu, Longchang Xie, Zhiming Li, Zhongmin Yuan
Cellular acetylation homeostasis is a kinetic balance precisely controlled by histone acetyl-transferase (HAT) and histone deacetylase (HDAC) activities. The loss of the counterbalancing function of basal HAT activity alters the precious HAT:HDAC balance towards enhanced histone deacetylation, resulting in a loss of acetylation homeostasis, which is closely associated with neuronal apoptosis. However, the critical HAT member whose activity loss contributes to neuronal apoptosis remains to be identified. In this study, we found that inactivation of GCN5 by either pharmacological inhibitors, such as CPTH2 and MB-3, or by inactivation with siRNAs leads to a typical apoptosis in cultured cerebellar granule neurons...
January 26, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28119367/hmga2-foxl2-axis-regulates-metastases-and-epithelial-to-mesenchymal-transition-of-chemo-resistant-gastric-cancer
#13
Jiaqiang Dong, Rui Wang, Gui Ren, Xiaowei Li, Jingbo Wang, Yi Sun, Jie Liang, Yongzan Nie, Kaichun Wu, Bin Feng, Yulong Shang, Daiming Fan
Purpose Chemo-resistance is the main cause of treatment failure in cancer and is associated with distant metastases and epithelial-to-mesenchymal transition (EMT). This study aimed to explore the mechanism of metastases and EMT in chemo-resistant gastric cancer (GC). Experimental Design A key molecular pathway was identified via gene profiling and a bioinformatic analysis in a chemo-resistant GC model. The roles of FOXL2, HMGA2 and ITGA2 were validated via loss-of-function and gain-of-function experiments in vitro and in an orthotopic GC animal model...
January 24, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28119125/galactosylated-polyaspartamide-copolymers-for-sirna-targeted-delivery-to-hepatocellular-carcinoma-cells
#14
Gennara Cavallaro, Rossella Farra, Emanuela Fabiola Craparo, Carla Sardo, Barbara Porsio, Gaetano Giammona, Francesca Perrone, Mario Grassi, Gabriele Pozzato, Gabriele Grassi, Barbara Dapas
The limited efficacy of available treatments for hepatocellular carcinoma (HCC) requires the development of novel therapeutic approaches. We synthesized a novel cationic polymer based on α,β-poly-(N-2-hydroxyethyl)-D,L-aspartamide (PHEA) for drug delivery to HCC cells. The copolymer was synthesized by subsequent derivatization of PHEA with diethylene triamine (DETA) and with a polyethylene glycol (PEG) derivative bearing galactose (GAL) molecules, obtaining the cationic derivative PHEA-DETA-PEG-GAL. PHEA-DETA-PEG-GAL has suitable chemical-physical characteristics for a potential systemic use and can effectively deliver a siRNA (siE2F1) targeted against the transcription factor E2F1, a gene product involved in HCC...
January 21, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28115855/long-noncoding-rna-crnde-functions-as-a-competing-endogenous-rna-to-promote-metastasis-and-oxaliplatin-resistance-by-sponging-mir-136-in-colorectal-cancer
#15
Hongyan Gao, Xiaodi Song, Ting Kang, Baohong Yan, Li Feng, Li Gao, Liang Ai, Xiaoni Liu, Jie Yu, Huiqi Li
Colorectal neoplasia differentially expressed (CRNDE) is a novel gene recognized as a long noncoding RNA (lncRNA) that is highly elevated in colorectal cancer and many other solid tumors but its functions on metastasis and oxaliplatin (OXA) resistance are unknown. In our study, we confirmed the upregulation of CRNDE in both primary specimens from colorectal cancer patients and colorectal cancer cell lines. Knockdown of CRNDE expression inhibited the migration and invasion potency of colorectal cancer cells with no effect on cell apoptosis...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28115244/identification-expression-pattern-and-functional-characterization-of-as-kip2-in-diapause-embryo-restarting-process-of-artemia-sinica
#16
Mengchen Zhang, Feng Yao, Tong Qin, Lin Hou, Xiangyang Zou
Proper control of the cellular processes requires a variety of regulatory proteins that are involved in the cell cycle, proliferation and apoptosis. Cyclin-dependent kinase inhibitor (CKI) negatively regulates transcription and arrests the cell cycle in G1 phase. KIP2 is a member of CKI family, which could inhibit proliferation by tight-binding with several cyclin-CDK complexes. During the embryonic development of the brine shrimp, Artemia sinica, KIP2 plays a key role in the cell cycle regulation, but the specific mechanisms remain unknown...
January 20, 2017: Gene
https://www.readbyqxmd.com/read/28108556/confirmation-of-five-novel-susceptibility-loci-for-systemic-lupus-erythematosus-sle-and-integrated-network-analysis-of-82-sle-susceptibility-loci
#17
Julio E Molineros, Wanling Yang, Xu-Jie Zhou, Celi Sun, Yukinori Okada, Huoru Zhang, Kek Heng Chua, Yu-Lung Lau, Yuta Kochi, Akari Suzuki, Kazuhiko Yamamoto, Jianyang Ma, So-Young Bang, Hye-Soon Lee, Kwangwoo Kim, Sang-Cheol Bae, Hong Zhang, Nan Shen, Loren L Looger, Swapan K Nath
We recently identified ten novel SLE susceptibility loci in Asians and uncovered several additional suggestive loci requiring further validation. This study aimed to replicate five of these suggestive loci in a Han Chinese cohort from Hong Kong, followed by meta-analysis (11,656 cases and 23,968 controls) on previously reported Asian and European populations, and perform bioinformatic analyses on all 82 reported SLE loci to identify shared regulatory signatures. We performed a battery of analyses for these five loci, as well as joint analyses on all 82 SLE loci...
January 20, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28104681/copy-number-variations-of-e2f1-a-new-genetic-risk-factor-for-testicular-cancer
#18
Maria Santa Rocca, Andrea Di Nisio, Arianna Marchiori, Marco Ghezzi, Giuseppe Opocher, Carlo Foresta, Alberto Ferlin
Testicular germ cell tumor (TGCT) is one of the most heritable forms of cancer. In last years many evidence suggested that constitutional genetic factors, mainly single nucleotide polymorphisms, can increase its risk. However, the possible contribution of copy-number variations (CNVs) in TGCT susceptibility has not been substantially addressed. Indeed, an increasing number of studies have focused on the effect of CNVs on gene expression and on the role of these structural genetic variations as risk factors for different forms of cancer...
January 19, 2017: Endocrine-related Cancer
https://www.readbyqxmd.com/read/28095325/peroxisome-proliferator-activated-receptor-%C3%AE-activation-inhibits-liver-growth-through-mir-122-mediated-downregulation-of-cmyc
#19
Andrei A Yarushkin, Yuliya A Kazantseva, Vyacheslav S Kobelev, Yuliya A Pustylnyak, Vladimir O Pustylnyak
Although NR1C3 agonists inhibit cell growth, the molecular mechanism of their action has not been thoroughly characterized to date. A recent study demonstrated that NR1C3 can regulate miR-122 by binding to its promoter. Given that miR-122 can indirectly regulate cMyc-mediated promitogenic signaling by targeting E2f1, we hypothesized that NR1C3 activation inhibits hepatocyte proliferation through miR-122-mediated cMyc downregulation. In the present study, we examined if liver hyperplasia induced by a strong chemical mitogen for the liver, 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP), which is an agonist of NR1I3, can be repressed by NR1C3 activation through miR-122 upregulation...
January 15, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28092370/api5-confers-cancer-stem-cell-like-properties-through-the-fgf2-nanog-axis
#20
K-H Song, H Cho, S Kim, H-J Lee, S J Oh, S R Woo, S-O Hong, H S Jang, K H Noh, C H Choi, J-Y Chung, S M Hewitt, J-H Kim, M Son, S-H Kim, B I Lee, H-C Park, Y-K Bae, T W Kim
Immune selection drives the evolution of tumor cells toward an immune-resistant and cancer stem cell (CSC)-like phenotype. We reported that apoptosis inhibitor-5 (API5) acts as an immune escape factor, which has a significant role in controlling immune resistance to antigen-specific T cells, but its functional association with CSC-like properties remains largely unknown. In this study, we demonstrated for the first time that API5 confers CSC-like properties, including NANOG expression, the frequency of CD44-positive cells and sphere-forming capacity...
January 16, 2017: Oncogenesis
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