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In vivo gene silencing

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https://www.readbyqxmd.com/read/29344928/morphine-mediated-brain-region-specific-astrocytosis-involves-the-er-stress-autophagy-axis
#1
Susmita Sil, Palsamy Periyasamy, Ming-Lei Guo, Shannon Callen, Shilpa Buch
A recent study from our lab has revealed a link between morphine-mediated autophagy and synaptic impairment. The current study was aimed at investigating whether morphine-mediated activation of astrocytes involved the ER stress/autophagy axis. Our in vitro findings demonstrated upregulation of GFAP indicating astrocyte activation with a concomitant increase in the production of proinflammatory cytokines in morphine-exposed human astrocytes. Using both pharmacological and gene-silencing approaches, it was demonstrated that morphine-mediated defective autophagy involved upstream activation of ER stress with subsequent downstream astrocyte activation via the μ-opioid receptor (MOR)...
January 17, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29341469/downregulation-of-csn6-attenuates-papillary-thyroid-carcinoma-progression-by-reducing-wnt-%C3%AE-catenin-signaling-and-sensitizes-cancer-cells-to-fh535-therapy
#2
Duo Wen, Tian Liao, Ben Ma, Ning Qu, Rong-Liang Shi, Zhong-Wu Lu, Yu-Long Wang, Wen-Jun Wei, Qing-Hai Ji
The incidence of thyroid cancer has increased worldwide at a rate higher than that of any other cancer. CSN6 is overexpressed in many types of cancers, and such expression is linked to oncogenic activity. However, the detailed biological functions of CSN6 in papillary thyroid cancer (PTC) have not been well characterized. We investigated CSN6 expression in PTC specimens and cell lines. We used short-hairpin RNA-mediated gene silencing to explore the biological effects of CSN6 depletion in PTC cells. The combined effects of CSN6 silencing and FH535 therapy were assessed in terms of cell viability...
January 17, 2018: Cancer Medicine
https://www.readbyqxmd.com/read/29339419/linc00152-down-regulated-mir-193a-3p-to-enhance-mcl1-expression-and-promote-gastric-cancer-cells-proliferation
#3
Yong Huang, Hui Luo, Fang Li, Yun'e Yang, Guangsheng Ou, Xiaolong Ye, Nianchu Li
The present work aimed to probe into the effect of long non-coding RNA (lncRNA) LINC00152 on gastric cancer (GC) cells proliferation by regulating miR-193a-3p and its target gene MCL1 Transfected si-LINC00152 was used to down-regulate LINC00152, and cells proliferation was measured by the CCK-8 assay. Cell apoptosis and cell cycle were analyzed by flow cytometry. Besides, we also detected the potential functional effects of differential expression of LINC00152 in vivo using nude mouse xenograft model. We overexpressed and down-expressed miR-193a-3p to study the in vitro effect of miR-193a-3p on GC cells proliferation and vitality...
January 16, 2018: Bioscience Reports
https://www.readbyqxmd.com/read/29339208/targeted-shrna-loaded-liposome-complex-combined-with-focused-ultrasound-for-blood-brain-barrier-disruption-and-suppressing-glioma-growth
#4
Guanjian Zhao, Qin Huang, Feng Wang, Xiang Zhang, Jiangang Hu, Ying Tan, Ning Huang, Zhigang Wang, Zhibiao Wang, Yuan Cheng
Our previous studies have demonstrated that focused ultrasound (FUS) combined with DNA-loaded microbubbles (MBs) can induce noninvasive, reversible, local disruption of the blood brain barrier (BBB) and enable targeted exogenous gene transfer into the central nervous system. However, due to low gene loading or the absence of positive targeting, to date, there has been no therapeutic effect of MBs combined with FUS in tumor treatment. In the current study, we adopted a phospholipid complex that exhibited sufficient gene loading and peptide-mediated targeting to delay glioma growth...
January 12, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29339188/the-enhancement-of-siplk1-penetration-across-bbb-and-its-anti-glioblastoma-activity-in-vivo-by-magnet-and-transferrin-co-modified-nanoparticle
#5
Dao-Zhou Liu, Ying Cheng, Rong-Qiao Cai, Wen-Wen Wang, Han Cui, Miao Liu, Bang-le Zhang, Qi-Bing Mei, Si-Yuan Zhou
In order to enhance the penetration of small interference RNA against the polo-like kinase I (siPLK1) across BBB to treat glioblastoma (GBM), transferrin (Tf) modified magnetic nanoparticle (Tf-PEG-PLL/MNP@siPLK1) was prepared. The in vitro experiments indicated that Tf-PEG-PLL/MNP@siPLK1 enhanced the cellular uptake of siPLK1, which resulted in an increase of gene silencing effect and cytotoxicity of Tf-PEG-PLL/MNP@siPLK1 on U87 cells. Besides, Tf-PEG-PLL/MNP@siPLK1 significantly inhibited the growth of U87 glioblastoma spheroids and markedly increased the BBB penetration efficiency of siPLK1 with the application of external magnetic field in in-vitro BBB model...
January 12, 2018: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/29338543/lucidone-suppresses-dengue-viral-replication-through-the-induction-of-heme-oxygenase-1
#6
Wei-Chun Chen, Chin-Kai Tseng, Chun-Kuang Lin, Shen-Nien Wang, Wen-Hung Wang, Shih-Hsien Hsu, Yu-Hsuan Wu, Ling-Chien Hung, Yen-Hsu Chen, Jin-Ching Lee
Dengue virus (DENV) infection causes life-threatening diseases such as dengue hemorrhagic fever and dengue shock syndrome. Currently, there is no effective therapeutic agent or vaccine against DENV infection; hence, there is an urgent need to discover anti-DENV agents. The potential therapeutic efficacy of lucidone was first evaluated in vivo using a DENV-infected Institute of Cancer Research (ICR) suckling mouse model by monitoring body weight, clinical score, survival rate, and viral titer. We found that lucidone effectively protected mice from DENV infection by sustaining survival rate and reducing viral titers in DENV-infected ICR suckling mice...
January 17, 2018: Virulence
https://www.readbyqxmd.com/read/29338191/conjugate-polyplexes-with-anti-invasive-properties-and-improved-sirna-delivery-in-vivo
#7
Yi Chen, Jing Li, David Oupický
This study reports on a simple method to prepare siRNA-polycation conjugate polyplexes by in situ thiol-disulfide exchange reaction. The conjugate polyplexes are prepared using thiol-terminated siRNA and a bioreducible branched polycationic inhibitor of the CXCR4 chemokine receptor (rPAMD). The rPAMD-SS-siRNA conjugate polyplexes exhibit improved colloidal stability and resistance against disassembly with heparin, serum, and physiological salt concentrations when compared with control conventional rPAMD/siRNA polyplexes...
January 17, 2018: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/29337531/a-branched-glycerol-based-copolymer-with-ultrahigh-p65-sirna-delivery-efficiency-for-enhanced-cancer-therapy
#8
Li Zhou, Xiaoyan Qu, Yi Guo, Min Wang, Bo Lei, Peter X Ma
The small interfering RNA (siRNA) is emerging as a potential therapeutic for the treatment of various diseases, because of the targeted gene silencing capability. The suppression of p65 expression has shown great potential in various cancer treatments. However, various substantial obstacles limit their clinical applications, including low cellular uptake, instability and cytotoxicity of delivery vehicles. We show a highly branched and biocompatible glycerol-based copolymer (HBGCs) to effectively deliver siRNA for excellent p65 gene silencing and safe lung cancer treatment in vitro and in vivo...
January 16, 2018: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/29331027/mir-137-functions-as-a-tumor-suppressor-in-pancreatic-cancer-by-targeting-mrgbp
#9
Feng Ding, Shuang Zhang, Shaoyang Gao, Jian Shang, Yanxia Li, Ning Cui, Qiu Zhao
miRNAs are small noncoding RNAs that act as critical epigenetic regulators in tumor carcinogenesis. In this study, our data showed that miR-137 was significantly downregulated in 58 pairs of human pancreatic cancer (PanCa) tissues and PanCa cell lines. Furthermore, the deregulated miR-137 was correlated with increased tumor size, higher TNM stage, and worse prognosis in pancreatic cancer. Functional studies demonstrated that overexpression of miR-137 dramatically suppressed cell proliferation and induced cell apoptosis in vitro...
January 13, 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29330145/mbd2-ablation-impairs-lymphopoiesis-and-impedes-progression-and-maintenance-of-t-all
#10
Mi Zhou, Kuangguo Zhou, Ling Cheng, Xing Chen, Jue Wang, Xiao-Min Wang, Yingchi Zhang, Qilin Yu, Shu Zhang, Di Wang, Liang Huang, Mei Huang, Ding Ma, Tao Cheng, Cong-Yi Wang, Weiping Yuan, Jianfeng Zhou
Aberrant DNA methylation patterns in leukemia might be exploited for therapeutic targeting. In this study, we employed a genetically deficient mouse model to explore the role of the methylated DNA binding protein MBD2 in normal and malignant hematopoiesis. MBD2 ablation led to diminished lymphocytes. Functional defects of the lymphoid compartment were also observed after in vivo reconstitution of MBD2-deficient hematopoietic stem cells (HSC). In an established model of Notch1-driven T cell acute lymphoblastic leukemia (T-ALL), MBD2 ablation impeded malignant progression and maintenance by attenuating the Wnt signaling pathway...
January 12, 2018: Cancer Research
https://www.readbyqxmd.com/read/29329415/establishment-of-a-three-dimensional-model-to-study-human-uterine-angiogenesis
#11
Camille L Duran, Colette A Abbey, Kayla J Bayless
STUDY QUESTION: Can primary human uterine microvascular endothelial cells (UtMVECs) be used as a model to study uterine angiogenic responses in vitro that are relevant in pregnancy? SUMMARY ANSWER: UtMVECs demonstrated angiogenic responses when stimulated with proangiogenic factors, including sphingosine 1-phosphate (S1P), vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), physiological levels of wall shear stress (WSS), human chorionic gonadotropin (hCG) and various combinations of estrogen and progesterone...
December 21, 2017: Molecular Human Reproduction
https://www.readbyqxmd.com/read/29327939/blockade-of-the-complement-c5a-c5ar1-axis-impairs-lung-cancer-bone-metastasis-by-cxcl16-mediated-effects
#12
Daniel Ajona, Carolina Zandueta, Leticia Corrales, Haritz Moreno, María J Pajares, Sergio Ortiz-Espinosa, Elena Martínez-Terroba, Naiara Perurena, Fernando J de Miguel, Eloisa Jantus-Lewintre, Carlos Camps, Silvestre Vicent, Jackeline Agorreta, Luis M Montuenga, Ruben Pio, Fernando Lecanda
RATIONALE: C5aR1(CD88), a receptor for complement anaphylatoxin C5a, is a potent immune mediator. Its impact on malignant growth and dissemination of NSCLC cells is poorly understood. OBJECTIVES: To investigate the contribution of the C5a/C5aR1 axis to the malignant phenotype of NSCLC cells, particularly in skeletal colonization, a preferential lung metastasis site. METHODS: Association between C5aR1 expression and clinical outcome was assessed in silico and validated by immunohistochemistry...
January 12, 2018: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/29327101/fundamentals-of-sirna-and-mirna-therapeutics-and-a-review-of-targeted-nanoparticle-delivery-systems-in-breast-cancer
#13
REVIEW
Tamkin Ahmadzada, Glen Reid, David R McKenzie
Gene silencing via RNA interference (RNAi) is rapidly evolving as a personalized approach to cancer treatment. The effector molecules-small interfering RNAs (siRNAs) and microRNAs (miRNAs)-can be used to silence or "switch off" specific cancer genes. Currently, the main barrier to implementing siRNA- and miRNA-based therapies in clinical practice is the lack of an effective delivery system that can protect the RNA molecules from nuclease degradation, deliver to them to tumor tissue, and release them into the cytoplasm of the target cancer cells, all without inducing adverse effects...
January 11, 2018: Biophysical Reviews
https://www.readbyqxmd.com/read/29321665/fhl2-interacts-with-egfr-to-promote-glioblastoma-growth
#14
Lili Sun, Shuye Yu, Hui Xu, Yanwen Zheng, Juntang Lin, Meiyan Wu, Jide Wang, Aidong Wang, Qing Lan, Frank Furnari, Webster Cavenee, Benjamin Purow, Ming Li
Four-and-a-half LIM protein2 (FHL2) is a member of the LIM-only protein family, which plays a critical role in tumorigenesis. We previously reported that FHL2 is upregulated and plays an oncogenic role in glioblastoma (GBM), the most common and aggressive brain tumor. GBM is also marked by amplification of the epidermal growth factor receptor (EGFR) gene and its mutations, of which EGFRvIII is the most common and functionally significant. Here we report that FHL2 physically interacts with the wild-type EGFR and its mutated EGFRvIII form in GBM cells...
January 11, 2018: Oncogene
https://www.readbyqxmd.com/read/29321164/kras-oncoprotein-expression-is-regulated-by-a-self-governing-eif5a-peak1-feed-forward-regulatory-loop
#15
Ken Fujimura, Huawei Wang, Felicia Watson, Richard L Klemke
There remains intense interest in tractable approaches to target or silence the KRAS oncoprotein as a rational therapeutic strategy to attack pancreatic adenocarcinoma (PDAC) and other cancers which overexpress it. Here we provide evidence that accumulation of the KRAS oncoprotein is controlled by a self-regulating feed-forward regulatory loop that utilizes a unique hypusinated isoform of the translation elongation factor eIF5A and the tyrosine kinase PEAK1. Oncogenic activation of KRAS increased eIF5A-PEAK1 translational signaling, which in turn facilitated increased KRAS protein synthesis...
January 10, 2018: Cancer Research
https://www.readbyqxmd.com/read/29317822/novel-functionalized-nanoparticles-for-tumor-targeting-co-delivery-of-doxorubicin-and-sirna-to-enhance-cancer-therapy
#16
Yu Xia, Tiantian Xu, Changbing Wang, Yinghua Li, Zhengfang Lin, Mingqi Zhao, Bing Zhu
Human homeobox protein (Nanog) is highly expressed in most cancer cells and has gradually emerged as an excellent target in cancer therapy, owing to its regulation of cancer cell proliferation, metastasis and apoptosis. In this study, we prepared tumor-targeting functionalized selenium nanoparticles (RGDfC-SeNPs) to load chemotherapeutic doxorubicin (DOX) and Nanog siRNA. Herein, RGDfC peptide was used as a tumor-targeting moiety which could specifically bind to αvβ3 integrins overexpressed on various cancer cells...
2018: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/29316746/vegf-sirna-delivery-by-a-cancer-specific-cell-penetrating-peptide
#17
Young Woong Lee, Young Eun Hwang, Ju Young Lee, Jung-Hoon Sohn, Bong Hyun Sung, Sun Chang Kim
RNA interference provides an effective tool for developing antitumor therapies. Cell-penetrating peptides (CPPs) are delivery vectors widely used to efficiently transport small-interfering RNA (siRNA) to intracellular targets. In this study, we investigated the efficacy of the cancer-specific CPP carrier BR2 to specifically transport siRNA to cancer-target cells. Our results showed that BR2 formed a complex with anti-vascular endothelial growth factor siRNA (siVEGF) that exhibited the appropriate size and surface charge for in vivo treatment...
January 11, 2018: Journal of Microbiology and Biotechnology
https://www.readbyqxmd.com/read/29314203/lncrna-pcat-1-promotes-tumour-growth-and-chemoresistance-of-oesophageal-cancer-to-cisplatin
#18
Qiang Zhen, Li-Na Gao, Ren-Feng Wang, Wei-Wei Chu, Ya-Xiao Zhang, Xiao-Jian Zhao, Bao-Lei Lv, Jia-Bao Liu
Oesophageal cancer (OC) is one of the most fatal malignancies in the world, and chemoresistance restricts the therapeutic outcome of OC. Long noncoding RNA (lncRNA) was reported to play roles in multiple cancer types. Yet, the function of lncRNA in chemoresistance of OC has not been reported. A lncRNA gene, PCAT-1, showed higher expression in OC tissues, especially higher in secondary OC compared with normal mucosa tissues. Overexpression of PCAT-1 increased the proliferation rate and growth of OC cells. Inhibition of PCAT-1 decreased proliferation and growth of OC cells, and increased cisplatin chemosensitivity...
January 2018: Cell Biochemistry and Function
https://www.readbyqxmd.com/read/29313393/ultrasound-mediated-nanobubble-destruction-umnd-facilitates-the-delivery-of-a10-3-2-aptamer-targeted-and-sirna-loaded-cationic-nanobubbles-for-therapy-of-prostate-cancer
#19
Meng Wu, Hongyun Zhao, Liang Guo, Yiru Wang, Jiao Song, Xueli Zhao, Chongyan Li, Lan Hao, Dong Wang, Jie Tang
The Forkhead box M1 (FoxM1) transcription factor is an important anti-tumor target. A novel targeted ultrasound (US)-sensitive nanobubble that is likely to make use of the physical energy of US exposure for the improvement of delivery efficacy to target tumors and specifically silence FoxM1 expression appears as among the most potential nanocarriers in respect of drug delivery. In this study, we synthesized a promising anti-tumor targeted FoxM1 siRNA-loaded cationic nanobubbles (CNBs) conjugated with an A10-3...
November 2018: Drug Delivery
https://www.readbyqxmd.com/read/29310682/upregulation-of-the-long-non-coding-rna-afap1-as1-affects-the-proliferation-invasion-and-survival-of-tongue-squamous-cell-carcinoma-via-the-wnt-%C3%AE-catenin-signaling-pathway
#20
Ze-You Wang, Min Hu, Min-Hui Dai, Jing Xiong, Shuai Zhang, Han-Jiang Wu, Shan-Shan Zhang, Zhao-Jian Gong
BACKGROUND: Long non-coding RNA (lncRNA) actin filament associated protein 1 antisense RNA1 (AFAP1-AS1) is oriented in an antisense direction to the protein-coding gene AFAP1 in the opposite strand. Previous studies showed that lncRNA AFAP1-AS1 was upregulated and acted as an oncogene in a variety of tumors. However, the expression and biological functions of lncRNA AFAP1-AS1 in tongue squamous cell carcinoma (TSCC) are still unknown. METHODS: The expression level of AFAP1-AS1 was measured in 103 pairs of human TSCC tissues and corresponding adjacent normal tongue mucous tissues...
January 8, 2018: Molecular Cancer
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