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In vivo gene silencing

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https://www.readbyqxmd.com/read/29144989/cysteine-dioxygenase-1-mediates-erastin-induced-ferroptosis-in-human-gastric-cancer-cells
#1
Shihui Hao, Jiang Yu, Wanming He, Qiong Huang, Yang Zhao, Bishan Liang, Shuyi Zhang, Zhaowei Wen, Shumin Dong, Jinjun Rao, Wangjun Liao, Min Shi
BACKGROUND: Ferroptosis is a recently discovered form of iron-dependent nonapoptotic cell death. It is characterized by loss of the activity of the lipid repair enzyme, glutathione peroxidase 4 (GPX4), and accumulation of lethal reactive lipid oxygen species. However, we still know relatively little about ferroptosis and its molecular mechanism in gastric cancer (GC) cells. Here, we demonstrate that erastin, a classic inducer of ferroptosis, induces this form of cell death in GC cells and that cysteine dioxygenase 1 (CDO1) plays an important role in this process...
November 13, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/29137288/elevated-timp-1-expression-is-associated-with-a-prometastatic-phenotype-disease-relapse-and-poor-survival-in-neuroblastoma
#2
Pritha Paul, Eric J Rellinger, Jingbo Qiao, Sora Lee, Natasha Volny, Chandrasekhar Padmanabhan, Carmelle V Romain, Bret Mobley, Hernan Correa, Dai H Chung
Approximately two-thirds of patients with neuroblastoma are found to have metastatic disease at time of diagnosis with frequent skeletal, lymph node, central nervous system, and liver involvement. Using a serial in vivo splenic injection model, we have isolated an aggressive subclone (BE(2)-C/LM2) from MYCN-amplified neuroblastomas that demonstrate an enhanced propensity to develop metastatic liver lesions. BE(2)-C/LM2 subclone cells demonstrate increased adherent, soft agar colony and tumorsphere growth in vitro...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29133857/pdgfr-modulated-mir-23b-cluster-and-mir-125a-5p-suppress-lung-tumorigenesis-by-targeting-multiple-components-of-kras-and-nf-kb-pathways
#3
Srivatsava Naidu, Lei Shi, Peter Magee, Justin D Middleton, Alessandro Laganá, Sudhakar Sahoo, Hui Sun Leong, Melanie Galvin, Kristopher Frese, Caroline Dive, Vincenza Guzzardo, Matteo Fassan, Michela Garofalo
In NSCLC alterations in PDGF receptors are markers of worst prognosis and efficient targeting of these receptors is yet to be achieved. In this study, we explored PDGFR-regulated microRNAs demonstrating that miR-23b cluster and miR-125a-5p are downregulated by increased expression of PDGFR-α or PDGFR-β in NSCLC cells. Mechanistically, the expression of these microRNAs is positively regulated by p53 and negatively modulated by NF-kB p65. Forced expression of miR-23b cluster or miR-125a-5p enhanced drug sensitivity and suppressed invasiveness of NSCLC cells by silencing several genes involved in oncogenic KRAS and NF-kB pathways, including SOS1, GRB2, IQGAP1, RALA, RAF-1, IKKβ, AKT2, ERK2 and KRAS itself...
November 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29133573/the-rars-mad1l1-fusion-gene-induces-cancer-stem-cell-like-properties-and-therapeutic-resistance-in-nasopharyngeal-carcinoma
#4
Qian Zhong, Zhihua Liu, Zhi-Rui Lin, Ze-Dong Hu, Li Yuan, Yan-Min Liu, Ai-Jun Zhou, Li-Hua Xu, Li-Juan Hu, Zi-Feng Wang, Xin Yuan Guan, Jia-Jie Hao, Vivian Wai Yan Lui, Ling Guo, Hai-Qiang Mai, Ming-Yuan Chen, Fei Han, Yun-Fei Xia, Jennifer R Grandis, Xing Zhang, Mu-Sheng Zeng
PURPOSE: Nasopharyngeal carcinoma (NPC) is most common head and neck cancer in Southeast Asia. Because local recurrence and distant metastasis are still the main causes of NPC treatment failure, it is urgent to identify new tumor markers and therapeutic targets for advanced NPC. EXPERIMENTAL DESIGN: RNA-seq was applied to look for interchromosome translocation in NPC. PCR, FISH and immunoprecipitation were used to examine the fusion gene expression at RNA, DNA, and protein levels in NPC biopsies...
November 13, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29128580/reduction-of-protein-phosphatase-2a-c%C3%AE-promotes-in-vivo-bone-formation-and-adipocyte-differentiation
#5
Kaya Yoshida, Jumpei Teramachi, Kenta Uchibe, Mika Ikegame, Lihong Qiu, Di Yang, Hirohiko Okamura
Serine/threonine protein phosphatase 2A (PP2A) regulates diverse physiological processes such as cell cycle, growth, apoptosis, and signal transduction. Previously, we demonstrated that silencing of the α-isoform of PP2A catalytic subunit (PP2A Cα) in osteoblasts accelerated osteoblast differentiation, whereas its overexpression suppressed differentiation. In this study, we examined the role of PP2A Cα in in vivo bone formation by generating transgenic mice (PP2A-Tg), in which the dominant negative form of PP2A Cα was specifically expressed in osteoblasts...
November 8, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/29128099/regulation-of-cellular-senescence-by-mir-34a-in-alcoholic-liver-injury
#6
Ying Wan, Kelly McDaniel, Nan Wu, Sugeily Ramos-Lorenzo, Trenton Glaser, Julie Venter, Heather Francis, Lindsey Kennedy, Keisaku Sato, Tianhao Zhou, Konstantina Kyritsi, Qiaobing Huang, Tami Annable, Chaodong Wu, Shannon Glaser, Gianfranco Alpini, Fanyin Meng
Alcoholic liver disease remains a major cause of liver-related morbidity and mortality, which ranges from alcoholic steatohepatitis to fibrosis/cirrhosis and hepatocellular carcinoma, and the related mechanisms are understood poorly. In this study, we aimed to investigate the role of miR-34a in alcohol-induced cellular senescence and liver fibrosis. We found that hepatic miR-34a expression was upregulated in ethanol-fed mice and heavy drinkers with steatohepatitis compared with respective controls. Mice treated with miR-34a Vivo-Morpholino developed less severe liver fibrosis than wild-type mice after 5 weeks of ethanol feeding...
November 2, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/29124315/the-class-i-iv-hdac-inhibitor-mocetinostat-increases-tumor-antigen-presentation-decreases-immune-suppressive-cell-types-and-augments-checkpoint-inhibitor-therapy
#7
David Briere, Niranjan Sudhakar, David M Woods, Jill Hallin, Lars D Engstrom, Ruth Aranda, Harrah Chiang, Andressa L Sodré, Peter Olson, Jeffrey S Weber, James G Christensen
Checkpoint inhibitor therapy has led to major treatment advances for several cancers including non-small cell lung cancer (NSCLC). Despite this, a significant percentage of patients do not respond or develop resistance. Potential mechanisms of resistance include lack of expression of programmed death ligand 1 (PD-L1), decreased capacity to present tumor antigens, and the presence of an immunosuppressive tumor microenvironment. Mocetinostat is a spectrum-selective inhibitor of class I/IV histone deacetylases (HDACs), a family of proteins implicated in epigenetic silencing of immune regulatory genes in tumor and immune cells...
November 9, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29119846/carbonate-apatite-nanoparticles-carry-sirna-s-targeting-growth-factor-receptor-genes-egfr1-and-erbb2-to-regress-mouse-breast-tumor
#8
Snigdha Tiash, Nur Izyani Binti Kamaruzman, Ezharul Hoque Chowdhury
Cancer cells lose their control on cell cycle by numerous genetic and epigenetic alterations. In a tumor, these cells highly express growth factor receptors (GFRs), eliciting growth, and cell division. Among the GFRs, epidermal growth factor receptor-1 (EGFR1) (Her1/ERBB1) and epidermal growth factor receptor-2 (EGFR2) (Her2/ERBB2) from epidermal growth factor (EGF) family and insulin-like growth factor-1 receptor (IGF1R) are highly expressed on breast cancer cells, thus contributing to the aggressive growth and invasiveness, have been focused in this study...
November 2017: Drug Delivery
https://www.readbyqxmd.com/read/29118335/adam9-promotes-lung-cancer-progression-through-vascular-remodeling-by-vegfa-angpt2-and-plat
#9
Chen-Yuan Lin, Chia-Fong Cho, Shih-Ting Bai, Jing-Pei Liu, Ting-Ting Kuo, Li-Ju Wang, Yu-Sen Lin, Ching-Chan Lin, Liang-Chuan Lai, Tzu-Pin Lu, Chih-Ying Hsieh, Chin-Nan Chu, Da-Chuan Cheng, Yuh-Pyng Sher
Lung cancer has a very high prevalence of brain metastasis, which results in a poor clinical outcome. Up-regulation of a disintegrin and metalloproteinase 9 (ADAM9) in lung cancer cells is correlated with metastasis to the brain. However, the molecular mechanism underlying this correlation remains to be elucidated. Since angiogenesis is an essential step for brain metastasis, microarray experiments were used to explore ADAM9-regulated genes that function in vascular remodeling. The results showed that the expression levels of vascular endothelial growth factor A (VEGFA), angiopoietin-2 (ANGPT2), and tissue plasminogen activator (PLAT) were suppressed in ADAM9-silenced cells, which in turn leads to decreases in angiogenesis, vascular remodeling, and tumor growth in vivo...
November 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29117631/astrocyte-elevated-gene-1-promotes-invasion-and-epithelial-mesenchymal-transition-in-bladder-cancer-cells-through-activation-of-signal-transducer-and-activator-of-transcription-3
#10
Xiaoming Yang, Lei Shi, Chengzhi Yi, Yang Yang, Liansheng Chang, Dongkui Song
OBJECTIVES: To determine the impact of astrocyte elevated gene-1 on the invasion and epithelial-mesenchymal transition of bladder cancer cells in vitro and metastasis in vivo. METHODS: Gain- and loss-of-function studies were carried out to investigate the biological roles of astrocyte elevated gene-1 in bladder cancer cell invasion, epithelial-mesenchymal transition and lung metastasis. The mechanism underlying the activity of astrocyte elevated gene-1 was examined...
November 8, 2017: International Journal of Urology: Official Journal of the Japanese Urological Association
https://www.readbyqxmd.com/read/29116339/%C3%AE-arrestin-1-deficiency-ameliorates-renal-interstitial-fibrosis-by-blocking-wnt1-%C3%AE-catenin-signaling-in-mice
#11
Huiyan Xu, Quanxin Li, Jiang Liu, Jiaqing Zhu, Liang Li, Ziying Wang, Yan Zhang, Yu Sun, Jinpeng Sun, Rong Wang, Fan Yi
Despite substantial progress being made in understanding the mechanisms contributing to the pathogenesis of renal fibrosis, there are only a few therapies available to treat or prevent renal fibrosis in clinical use today. Therefore, identifying the key cellular and molecular mediators involved in the pathogenesis of renal fibrosis will provide new therapeutic strategy for treating patients with chronic kidney disease (CKD). β-Arrestin-1, a member of β-arrestin family, not only is a negative adaptor of G protein-coupled receptors (GPCRs), but also acts as a scaffold protein and regulates a diverse array of cellular functions independent of GPCR activation...
November 7, 2017: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/29115546/influence-of-the-twist-gene-on-the-invasion-and-metastasis-of-colon-cancer
#12
Duowei Wang, Bikash Rai, Feng Qi, Tong Liu, Jinmiao Wang, Xiaodong Wang, Bozhao Ma
The present study investigated the role of the Twist gene in epithelial-mesenchymal transition (EMT) and its effects on the invasion and metastasis of malignant tumors. In vitro, we transfected SW480, HCT116 and HT29 cells with recombinant plasmids, pTracer-CMV/BSD-Twist and pGenesil1.2-Twist-shRNA, to influence expression of Twist. The transfection efficacy of the plasmids in the cell lines was confirmed by flow cytometry. The relative mRNA and protein expression levels of Twist, E-cadherin and vimentin in the transfected cells were detected by RT-PCR and western blotting, respectively...
November 6, 2017: Oncology Reports
https://www.readbyqxmd.com/read/29110682/tagln2-is-a-candidate-prognostic-biomarker-promoting-tumorigenesis-in-human-gliomas
#13
Ming-Zhi Han, Ran Xu, Yang-Yang Xu, Xin Zhang, Shi-Lei Ni, Bin Huang, An-Jing Chen, Yu-Zhen Wei, Shuai Wang, Wen-Jie Li, Qing Zhang, Gang Li, Xin-Gang Li, Jian Wang
BACKGROUND: Transgelin-2 (TAGLN2) is a member of the calponin family of actin-bundling proteins that is involved in the regulation of cell morphology, motility, and cell transformation. Here, the clinical significance and potential function of TAGLN2 in malignant gliomas were investigated. METHODS: Molecular and clinical data was obtained from The Cancer Genome Atlas (TCGA) database. Gene ontology and pathway analysis was used to predict potential functions of TAGLN2...
November 6, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/29109775/the-bidirectional-regulation-between-myl5-and-hif-1%C3%AE-promotes-cervical-carcinoma-metastasis
#14
Lan Zhang, Shu-Ting Huang, Yan-Ling Feng, Ting Wan, Hai-Feng Gu, Jing Xu, Lin-Jing Yuan, Yun Zhou, Xing-Juan Yu, Long Huang, Rong-Zhen Luo, Wei-Hua Jia, Min Zheng
Myosin light chains (MLC) serve important regulatory functions in a wide range of cellular and physiological processes. Recent research found that MLC are also chromatin-associated nuclear proteins which regulate gene transcription. In this study, the MLC member myosin regulatory light chain 5 (MYL5) expression was upregulated in late stage cervical cancer patients, positively correlated with pelvic lymph node metastasis, and identified as a poor survival indicator. MYL5 overexpression promoted metastasis in cervical cancer in vitro and in vivo models, whereas MYL5 silencing had the converse effect...
2017: Theranostics
https://www.readbyqxmd.com/read/29108243/silencing-heme-oxygenase-1-increases-the-sensitivity-of-abc-dlbcl-cells-to-histone-deacetylase-inhibitor-in-vitro-and-in-vivo
#15
Zhen Zhou, Qin Fang, Dan Ma, Nana Zhe, Mei Ren, Bingqing Cheng, Peifan Li, Ping Liu, Xiaojing Lin, Sishi Tang, Xiuying Hu, Yudan Liao, Yaming Zhang, Tingting Lu, Jishi Wang
Heme oxygenase-1 (HO-1) can promote tumor growth and reinforce the resistance of diffuse large B-cell lymphoma (DLBCL) cells to chemotherapeutic drug vincristine. We herein found that HO-1 protein expression was higher in high-risk DLBCL patients than in low-risk ones. Silencing HO-1 gene expression resisted vorinostat-induced apoptosis and arrested cell cycle in the G0/G1 phase of LY-10 cells. Western blot, co-immunoprecipitation and chromatin immunoprecipitation assays confirmed that the possible mechanisms may be increased cleaved caspase-3 protein expression, decreased phospho-histone deacetylase 3 protein expression, and activated histone acetylation of P27(Kip1) promoter...
October 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/29106514/functional-role-of-plce1-intronic-insertion-variant-associated-with-susceptibility-to-esophageal-squamous-cell-carcinoma
#16
Lixuan Wei, Mingming Shao, Yanjie Zhao, Jian Zheng, Jiahui Chu, Jiang Chang, Xinxin Cheng, Cui Qionghua, Linna Peng, Yingying Luo, Wenle Tan, Wen Tan, Dongxin Lin, Chen Wu
Genome-wide association studies have consistently identified PLCE1 as esophageal squamous-cell carcinoma (ESCC) susceptibility gene; however, the functional role of PLCE1 variants remains to be verified. In this study, we performed fine mapping of the PLCE1 region using our previous ESCC GWAS data and identified 33 additional risk variants in this susceptibility locus. Here, we report the functional characterization of a four-nucleotide insertion/deletion variation (rs71031566 C----/CATTT) in PLCE1 that was associated with risk of developing ESCC...
November 2, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/29106389/cul4b-promotes-gastric-cancer-invasion-and-metastasis-involvement-of-upregulation-of-her2
#17
M Qi, M Jiao, X Li, J Hu, L Wang, Y Zou, M Zhao, R Zhang, H Liu, J Mi, L Zhang, L Liu, Y Gong, B Han
Cullin 4B (CUL4B) is a scaffold protein overexpressed in several solid malignancies. It is known to silence tumor suppressor through post-transcriptional manner. However, its clinical significance and underlying molecular mechanisms in gastric cancer (GC) remain largely unknown. In this study, we found that CUL4B was significantly overexpressed in GC tissues and its overexpression was correlated with lymph node metastasis and poor prognosis. Through gain- and loss-of-function experiments, we showed that CUL4B promotes GC cell invasion and epithelial-mesenchymal transition (EMT) in vitro, as well as tumor growth and metastasis in vivo...
November 6, 2017: Oncogene
https://www.readbyqxmd.com/read/29106062/co-delivery-of-hif-1%C3%AE-sirna-and-5-fluorouracil-to-overcome-drug-resistance-in-gastric-cancer-sgc-7901-cells
#18
Yunna Chen, Li Sun, Dongdong Guo, Ziteng Wu, Weidong Chen
BACKGROUND: Drug resistance cancer cells have become a major problem in chemotherapy. To solve this problem co-delivery of siRNA and 5-fluorouracil chitosan nanoparticles were prepared to reverse the multidrug resistance of gastric cancer SGC-7901 cells in vitro. METHODS: Chitosan nanoparticles were prepared by ionic gel method. siRNA nanoparticles were characterized by gel retardation assays, particle size and zeta potential were measured to confirm nanoparticles formation...
November 6, 2017: Journal of Gene Medicine
https://www.readbyqxmd.com/read/29102563/tgf-%C3%AE-mediates-renal-fibrosis-via-the-smad3-erbb4-ir-long-noncoding-rna-axis
#19
Min Feng, Patrick Ming-Kuen Tang, Xiao-Ru Huang, Si-Fan Sun, Yong-Ke You, Jun Xiao, Lin-Li Lv, An-Ping Xu, Hui-Yao Lan
Transforming growth factor β (TGF-β)/Smad3 signaling plays a role in tissue fibrosis. We report here that Erbb4-IR is a novel long non-coding RNA (lncRNA) responsible for TGF-β/Smad3-mediated renal fibrosis and is a specific therapeutic target for chronic kidney disease. Erbb4-IR was induced by TGF-β1 via a Smad3-dependent mechanism and was highly upregulated in the fibrotic kidney of mouse unilateral ureteral obstructive nephropathy (UUO). Silencing Erbb4-IR blocked TGF-β1-induced collagen I and alpha-smooth muscle actin (α-SMA) expressions in vitro and effectively attenuated renal fibrosis in the UUO kidney by blocking TGF-β/Smad3 signaling...
October 5, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/29101238/glucocorticoid-resistance-is-reverted-by-lck-inhibition-in-pediatric-t-cell-acute-lymphoblastic-leukemia
#20
Valentina Serafin, Giorgia Capuzzo, Gloria Milani, Sonia Anna Minuzzo, Marica Pinazza, Roberta Bortolozzi, Silvia Bresolin, Elena Porcù, Chiara Frasson, Stefano Indraccolo, Giuseppe Basso, Benedetta Accordi
Pediatric T-acute lymphoblastic leukemia (T-ALL) patients often display resistance to glucocorticoid (GC) treatment. These patients, classified as Prednisone Poor Responders (PPR), have poorer outcome compared to the other pediatric T-ALL patients receiving a high-risk adapted therapy. Since glucocorticoids are administered to ALL patients during all the different phases of therapy, GC resistance represents an important challenge to be addressed in order to improve the outcome for these patients. Mechanisms underlying resistance are not yet fully unraveled, thus our research focused on the identification of deregulated signaling pathways to point out new targeted approaches...
November 3, 2017: Blood
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