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In vivo gene silencing

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https://www.readbyqxmd.com/read/28429540/silencing-of-astrocyte-elevated-gene-1-inhibits-proliferation-and-migration-and-induces-apoptosis-in-melanoma
#1
Yue Zhang, Ge Peng, Ying Wang, Lixia Cui, Wenqing Wu, Luan Wang, Chengyu Liu, Xiuping Han
Melanoma is an aggressive skin malignancy with a high mortality. Astrocyte elevated gene-1 (AEG-1), a downstream target of ras and c-myc, has been implicated in the development of multiple tumors, yet its role in melanoma remains unclear. In the present study, the role of AEG-1 in melanoma was explored through AEG-1 silencing. Our results showed that silencing of AEG-1 inhibited proliferation of melanoma cells and induced cell cycle arrest, accompanied by reduced levels of cyclinA, cyclinB, cyclinD1, cyclinE and cyclin dependent kinase 2...
April 21, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28428331/a-personalized-model-of-coq2-nephropathy-rescued-by-the-wild-type-coq2-allele-or-dietary-coenzyme-q10-supplementation
#2
Jun-Yi Zhu, Yulong Fu, Adam Richman, Zhanzheng Zhao, Patricio E Ray, Zhe Han
Clinical studies have identified patients with nephrotic syndrome caused by mutations in genes involved in the biosynthesis of coenzyme Q10 (CoQ10), a lipid component of the mitochondrial electron transport chain and an important antioxidant. However, the cellular mechanisms through which these mutations induce podocyte injury remain obscure. Here, we exploited the striking similarities between Drosophila nephrocytes and human podocytes to develop a Drosophila model of these renal diseases, and performed a systematic in vivo analysis assessing the role of CoQ10 pathway genes in renal function...
April 20, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28426969/chemogenetic-interrogation-of-a-brain-wide-fear-memory-network-in-mice
#3
Gisella Vetere, Justin W Kenney, Lina M Tran, Frances Xia, Patrick E Steadman, John Parkinson, Sheena A Josselyn, Paul W Frankland
Behavior depends on coordinated activity across multiple brain regions. Within such networks, highly connected hub regions are assumed to disproportionately influence behavioral output, although this hypothesis has not been systematically evaluated. Previously, by mapping brain-wide expression of the activity-regulated gene c-fos, we identified a network of brain regions co-activated by fear memory. To test the hypothesis that hub regions are more important for network function, here, we simulated node deletion in silico in this behaviorally defined functional network...
April 19, 2017: Neuron
https://www.readbyqxmd.com/read/28424246/enteropathy-associated-t-cell-lymphoma-subtypes-are-characterized-by-loss-of-function-of-setd2
#4
Andrea B Moffitt, Sarah L Ondrejka, Matthew McKinney, Rachel E Rempel, John R Goodlad, Chun Huat Teh, Sirpa Leppa, Susanna Mannisto, Panu E Kovanen, Eric Tse, Rex K H Au-Yeung, Yok-Lam Kwong, Gopesh Srivastava, Javeed Iqbal, Jiayu Yu, Kikkeri Naresh, Diego Villa, Randy D Gascoyne, Jonathan Said, Magdalena B Czader, Amy Chadburn, Kristy L Richards, Deepthi Rajagopalan, Nicholas S Davis, Eileen C Smith, Brooke C Palus, Tiffany J Tzeng, Jane A Healy, Patricia L Lugar, Jyotishka Datta, Cassandra Love, Shawn Levy, David B Dunson, Yuan Zhuang, Eric D Hsi, Sandeep S Dave
Enteropathy-associated T cell lymphoma (EATL) is a lethal, and the most common, neoplastic complication of celiac disease. Here, we defined the genetic landscape of EATL through whole-exome sequencing of 69 EATL tumors. SETD2 was the most frequently silenced gene in EATL (32% of cases). The JAK-STAT pathway was the most frequently mutated pathway, with frequent mutations in STAT5B as well as JAK1, JAK3, STAT3, and SOCS1 We also identified mutations in KRAS, TP53, and TERT Type I EATL and type II EATL (monomorphic epitheliotropic intestinal T cell lymphoma) had highly overlapping genetic alterations indicating shared mechanisms underlying their pathogenesis...
April 19, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28423732/long-intergenic-noncoding-rna-00673-promotes-non-small-cell-lung-cancer-metastasis-by-binding-with-ezh2-and-causing-epigenetic-silencing-of-hoxa5
#5
Chenhui Ma, Guannan Wu, Qingqing Zhu, Hongbing Liu, Yanwen Yao, Dongmei Yuan, Yafang Liu, Tangfeng Lv, Yong Song
Metastasis of cancer cells is a key impediment to favorable outcomes of cancer treatment. Functional roles of long noncoding RNAs in several biological processes, including metastasis, have recently been discovered. In our previous work, we reported a positive correlation of increased expression of linc00673 in NSCLC tissues with tumor size, lymph node metastasis, TNM stage, and increased proliferation of NSCLC cells, both, in vitro and in vivo. In this study, we demonstrate that ectopic expression of linc00673 promotes migration and invasion of NSCLC cells...
March 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423353/silencing-prdm14-expression-by-an-innovative-rnai-therapy-inhibits-stemness-tumorigenicity-and-metastasis-of-breast-cancer
#6
Hiroaki Taniguchi, Daisuke Hoshino, Chiharu Moriya, Hitoshi Zembutsu, Nobuhiro Nishiyama, Hiroyuki Yamamoto, Kazunori Kataoka, Kohzoh Imai
PR domain zinc finger protein 14 (PRDM14) maintains stemness in embryonic stem cells via epigenetic mechanisms. Although PRDM14 is elevated in several cancers, it is unclear if and how PRDM14 confers stem cell-like properties and epigenetic changes to cancer cells. Here, we examined the phenotypic characteristics and epigenetic and gene expression profiles of cancer cells that differentially express PRDM14, and assessed the potential of PRDM14-targeted cancer therapy. PRDM14 expression was markedly increased in many different cancer types and correlated with poor survival of breast cancer patients...
April 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28422734/silencing-of-karyopherin-%C3%AE-2-inhibits-cell-growth-and-survival-in-human-hepatocellular-carcinoma
#7
Yunfeng Yang, Jian Guo, Yuxia Hao, Fuhua Wang, Fengxia Li, Shaomin Shuang, Junping Wang
Karyopherin α2 (KPNA2), involved in nucleocytoplasmic transport, has been reported to be upregulated in hepatocellular carcinoma and considered as a biomarker for poor prognosis. However, comprehensive studies of KPNA2 functions in hepatocellular carcinogenesis are still lacking. Our study examine the roles and related molecular mechanisms of KPNA2 in hepatocellular carcinoma development. Results show that KPNA2 knockdown inhibited the proliferation and growth of hepatocellular carcinoma cells in vitro and in vivo...
March 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/28422198/multiplexed-gene-silencing-in-living-cells-and-in-vivo-using-a-dnazymes-coooh-nanocomposite
#8
Na Li, Yanli Li, Xiaonan Gao, Zhengze Yu, Wei Pan, Bo Tang
We demonstrate a novel DNAzymes-based nanocomposite that can simultaneously silence three types of genes in living cells and in vivo. The synergetic strategy for silencing three different genes can significantly enhance the knockdown efficacy and effectively inhibit the cancer cells' progression.
April 19, 2017: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/28420432/elevated-gab2-induces-tumor-growth-and-angiogenesis-in-colorectal-cancer-through-upregulating-vegf-levels
#9
Chenbo Ding, Junmin Luo, Xiaobo Fan, Longmei Li, Shanshan Li, Kunming Wen, Jihong Feng, Guoqiu Wu
BACKGROUND: Grb2-associated binder 2 (Gab2) is a scaffolding protein that serves as a critical signaling amplifier downstream of tyrosine kinase receptors. Our previous study has shown that Gab2 induces epithelial-to-mesenchymal transition (EMT) and promotes metastasis in colorectal cancer (CRC). However, the role of Gab2 in CRC growth and angiogenesis remains unclear. METHODS: The expression of vascular endothelial growth factor (VEGF) in different colorectal tissues was detected by immunohistochemistry and qRT-PCR to evaluate its correlation with Gab2...
April 18, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28420424/a-novel-lncrna-uc-134-represses-hepatocellular-carcinoma-progression-by-inhibiting-cul4a-mediated-ubiquitination-of-lats1
#10
Wen Ni, Yuqin Zhang, Zetao Zhan, Feng Ye, Yonghao Liang, Jing Huang, Keli Chen, Longhua Chen, Yi Ding
BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide, and tumor recurrence and metastasis are major factors that contribute to the poor outcome of patients with HCC. Long noncoding RNAs (lncRNAs) are known to regulate different tumorigenic processes, and a growing body of evidence indicates that Hippo kinase signaling is inactivated in many cancers. However, the upstream lncRNA regulators of Hippo kinase signaling in HCC are poorly understood. METHODS: Using a lncRNA microarray, we identified a novel lncRNA, uc...
April 19, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28419207/ckii-sirt1-sm22%C3%AE-loop-evokes-a-self-limited-inflammatory-response-in-vascular-smooth-muscle-cells
#11
Ya-Nan Shu, Li-Hua Dong, Han Li, Qian-Qian Pei, Sui-Bing Miao, Fan Zhang, Dan-Dan Zhang, Rong Chen, Ya-Juan Yin, Yan-Ling Lin, Zhen-Ying Xue, Pin Lv, Xiao-Li Xie, Li-Li Zhao, Xi Nie, Peng Chen, Mei Han
Aims: Sirtuin 1 (SIRT1) inhibits nuclear factor kappa B (NF-κB) activity in response to the inflammatory cytokine tumour necrosis factor alpha (TNF-α). Smooth muscle (SM) 22α is a phosphorylation-regulated suppressor of IKK-IκBα-NF-κB signalling cascades in vascular smooth muscle cells (VSMCs). Sm22α knockout results in increased expression of pro-inflammatory genes in the aortas which are controlled by NF-κB. This study aimed to investigate the relationship between SM22α and SIRT1 in the control of vascular inflammation...
April 16, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28418907/bh3-mimetics-and-bet-inhibitors-elicit-enhanced-lethality-in-malignant-glioma
#12
Chiaki Tsuge Ishida, Elena Bianchetti, Chang Shu, Marc-Eric Halatsch, Mike-Andrew Westhoff, Georg Karpel-Massler, Markus D Siegelin
Drug combination therapies remain pivotal for the treatment of heterogeneous malignancies, such as glioblastomas. Here, we show a novel lethal interaction between Bcl-xL and c-myc inhibition accomplished by bromodomain protein inhibitors. Established, patient-derived xenograft and stem cell-like glioma cells were treated with the novel bromodomain protein inhibitors, JQ1 and OTX015, along with BH3-mimetics, ABT263 or Obatoclax. Synergy was assessed by calculation of CI values. Small interfering RNAs (siRNAs) were used for gene silencing and mechanistic studies...
March 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28418770/gene-silencing-activity-and-hepatic-accumulation-of-antisense-oligonucleotides-bearing-cholesterol-conjugated-thiono-triester-at-the-gap-region
#13
Mado Nakajima, Takeshi Kasuya, Shinnichi Yokota, Reina Onishi, Tatsuya Ikehara, Akira Kugimiya, Ayahisa Watanabe
Cholesterol (Chol) conjugation to the 5' or 3' end of antisense oligonucleotide (ASO) enables delivery to the liver, and Chol conjugation at the gap region can also be expected to improve delivery to the liver. In this study, we synthesized ASOs bearing the Chol-conjugated thiono triester and evaluated their activity and hepatic accumulation. We found that Chol conjugations at the gap region improved in vitro activity and hepatic accumulation when compared to unconjugated ASOs. However, Chol conjugation with phosphorothioate linkage did not improve in vivo activity in the liver, suggesting the importance of cleaving the phosphodiester between ASO and Chol...
April 18, 2017: Nucleic Acid Therapeutics
https://www.readbyqxmd.com/read/28418107/a-new-path-in-defining-light-parameters-for-hair-growth-discovery-and-modulation-of-photoreceptors-in-human-hair-follicle
#14
Serena Buscone, Andrei N Mardaryev, Bianca Raafs, Jan W Bikker, Carsten Sticht, Norbert Gretz, Nilofer Farjo, Natallia E Uzunbajakava, Natalia V Botchkareva
BACKGROUND AND OBJECTIVE: Though devices for hair growth based on low levels of light have shown encouraging results, further improvements of their efficacy is impeded by a lack of knowledge on the exact molecular targets that mediate physiological response in skin and hair follicle. The aim of this study was to investigate the expression of selected light-sensitive receptors in the human hair follicle and to study the impact of UV-free blue light on hair growth ex vivo. MATERIAL AND METHODS: The expression of Opsin receptors in human skin and hair follicles has been characterized using RT-qPCR and immunofluorescence approaches...
April 18, 2017: Lasers in Surgery and Medicine
https://www.readbyqxmd.com/read/28416840/-b7-h3-silencing-inhibits-human-hematological-malignancy-xenograft-tumor-tumorigenesis-and-metastasis-in-nude-mice
#15
X X Yan, W Zhang, J Wang, X Y Ke
OBJECTIVE: To investigate the effect and mechanism of targeted B7-H3 gene silencing on the tumorigenesis and metastasis of human hematological malignancy xenograft tumor in nude mice. METHODS: Real-time fluorogentic quantitative PCR (qPCR) and flow cytometry (FCM) were used to detect the expression of B7-H3 in 13 strains of malignant hematologic cells. Then, U937, Maver and Z138 cells which expressed high level of B7-H3 were screened out. Targeted B7-H3 knockdown in U937, Maver and Z138 was performed by lentivirus transduction and the effect of B7-H3 silencing in stable cell lines was tested by qPCR and FCM...
April 18, 2017: Beijing da Xue Xue Bao. Yi Xue Ban, Journal of Peking University. Health Sciences
https://www.readbyqxmd.com/read/28408137/4-acetylantroquinonol-b-suppresses-autophagic-flux-and-improves-cisplatin-sensitivity-in-highly-aggressive-epithelial-cancer-through-the-pi3k-akt-mtor-p70s6k-signaling-pathway
#16
Mingche Liu, Oluwaseun Adebayo Bamodu, Wen-Chien Huang, Muhammad Ary Zucha, Yen-Kuang Lin, Alexander T H Wu, Chun-Chih Huang, Wei-Hwa Lee, Chiou-Chung Yuan, M Hsiao, Li Deng, Yew-Min Tzeng, Chi-Tai Yeh
Targeting residual self-renewing, chemoresistant cancerous cells may represent the key to overcoming therapy resistance. The entry of these quiescent cells into an activated state is associated with high metabolic demand and autophagic flux. Therefore, modulating the autophagy pathway in aggressive carcinomas may be beneficial as a therapeutic modality. In this study, we evaluated the anti-tumor activities of 4-acetylantroquinonol B (4-AAQB) in chemoresistant ovarian cancer cells, particularly its ability to modulate autophagy through autophagy-related genes (Atg)...
April 10, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28404917/expression-and-functional-regulation-of-stemness-gene-lgr5-in-esophageal-squamous-cell-carcinoma
#17
Zhuan Lv, Yu Jane J, Wei-Jie Zhang, Li Xiong, Feng Wang, Li-Feng Li, Xue-Liang Zhou, Xin-Ya Gao, Xian-Fei Ding, Li Han, Ya-Fei Cai, Wang Ma, Liu-Xing Wang
Cancer stem cells (CSCs) are defined as a rare subpopulation of undifferentiated cells with biological characteristics that include the capacity for self-renewal, differentiation into various lineages, and tumor initiation. To explore the mechanism of CSCs in esophageal squamous cell carcinoma (ESCC), we focused on Leucine-rich repeat containing G protein-coupled receptor 5 (Lgr5), a target gene of the Wnt signaling pathway, which has been identified as a marker of intestinal stem cells and shown to be overexpressed in several human malignancies...
February 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28404587/cic-dux4-induces-small-round-cell-sarcomas-distinct-from-ewing-sarcoma
#18
Toyoki Yoshimoto, Miwa Tanaka, Mizuki Homme, Yukari Yamazaki, Yutaka Takazawa, Cristina R Antonescu, Takuro Nakamura
CIC-DUX4 sarcoma (CDS) or CIC-rearranged sarcoma is a  subcategory of small round cell sarcoma resembling the morphological phenotypes of Ewing sarcoma (ES). Hoever, recent clinicopathologic and molecular genetic analyses indicate that CDS is an independent disease entity from ES. Few ancillary markers have been used in the differential diagnosis of CDS, and additional CDS-specific biomarkers are needed for more definitive classification. Here we report the generation of an ex vivo mouse model for CDS by transducing embryonic mesenchymal cells (eMC) with human CIC-DUX4 cDNA...
April 12, 2017: Cancer Research
https://www.readbyqxmd.com/read/28400112/endothelial-specific-deletion-of-autophagy-related-7-atg7-attenuates-arterial-thrombosis-in-mice
#19
Jonathan W Yau, Krishna K Singh, Yan Hou, Xi Lei, Azza Ramadan, Adrian Quan, Hwee Teoh, Wolfgang M Kuebler, Mohammed Al-Omran, Bobby Yanagawa, Heyu Ni, Subodh Verma
BACKGROUND: Thrombosis persists as a leading cause of morbidity and mortality. Given that endothelial cells (ECs) play a central role in regulating thrombosis, understanding the molecular endothelial cues that regulate susceptibility or resistance to thrombosis have important translational implications. Accordingly, we evaluated the role of endothelial autophagy in the development of thrombosis. METHODS: We generated mice in which the essential autophagy-related 7 (ATG7) gene was conditionally deleted from ECs (EC-ATG7(-/-) mice)...
March 16, 2017: Journal of Thoracic and Cardiovascular Surgery
https://www.readbyqxmd.com/read/28398453/multi-step-encapsulation-of-chemotherapy-and-gene-silencing-agents-in-functionalized-mesoporous-silica-nanoparticles
#20
Jianliang Shen, Haoran Liu, Chaofeng Mu, Joy Wolfram, Wei Zhang, Han-Cheon Kim, Guixian Zhu, Zhongbo Hu, Liang-Nian Ji, Xuewu Liu, Mauro Ferrari, Zong-Wan Mao, Haifa Shen
Drug to carrier ratio is an important consideration in designing drug platforms, since a low loading capacity necessitates the use of high doses of carriers, which can result in side effects. Here, we have engineered a platform to co-deliver small molecule drugs and small interfering RNA (siRNA). This platform consists of cyclodextrin-grafted polyethylenimine (CP) functionalized mesoporous silica nanoparticles (MSNP). A unique multi-step encapsulation procedure was used to obtain a high loading capacity for doxorubicin (DOX) and siRNA oligos specific for the PKM2 gene that encodes pyruvate kinase M2, an enzyme catalyzing the final rate-limiting step in glycolysis...
April 20, 2017: Nanoscale
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