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In vivo gene silencing

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https://www.readbyqxmd.com/read/28240870/a-multifunctional-envelope-type-sirna-delivery-nanoparticle-platform-for-prostate-cancer-therapy
#1
Xiaoding Xu, Jun Wu, Yanlan Liu, Phei Er Saw, Wei Tao, Mikyung Yu, Harshal R Zope, Michelle Si, Amanda Victorious, Jonathan Rasmussen, Dana Ayyash, Omid C Farokhzad, Jinjun Shi
With the capability of specific silencing of target gene expression, RNA interference (RNAi) technology is emerging as a promising therapeutic modality for the treatment of cancer and other diseases. One key challenge for the clinical applications of RNAi is the safe and effective delivery of RNAi agents such as small interfering RNA (siRNA) to a particular non-liver diseased tissue (e.g., tumor) and cell type with sufficient cytosolic transport. In this work, we proposed a multifunctional envelope-type nanoparticle (NP) platform for prostate cancer (PCa)-specific in vivo siRNA delivery...
February 27, 2017: ACS Nano
https://www.readbyqxmd.com/read/28238126/quantification-of-sirna-duplexes-bound-to-gold-nanoparticle-surfaces
#2
Jilian R Melamed, Rachel S Riley, Danielle M Valcourt, Margaret M Billingsley, Nicole L Kreuzberger, Emily S Day
RNA interference (RNAi)-based gene regulation has recently emerged as a promising strategy to silence genes that drive disease progression. RNAi is typically mediated by small interfering ribonucleic acids (siRNAs), which, upon delivery into the cell cytoplasm, trigger degradation of complementary messenger RNA molecules to halt production of their encoded proteins. While RNAi has enormous clinical potential, its in vivo utility has been hindered because siRNAs are rapidly degraded by nucleases, cannot passively enter cells, and are quickly cleared from the bloodstream...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28237093/mir-26a-enhances-invasive-capacity-by-suppressing-gsk3%C3%AE-in-human-lung-cancer-cells
#3
Gaoyang Lin, Boning Liu, Zhaowei Meng, Yunde Liu, Xuebing Li, Xiang Wu, Qinghua Zhou, Ke Xu
Lung cancer is the common cause of death from cancer, and most lung cancer patients die of metastasis. MicroRNAs (miRNAs) function as either oncogenes or tumor suppressors, playing crucial role not only in tumorigenesis, but also in tumor invasion and metastasis. There are several studies showed that miR-26a is involved in carcinogenesis, however, its role in tumor metastasis need to be elucidated. In this study, we showed that ectopic expression of miR-26a enhanced migration and invasion of lung cancer cells...
February 21, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28236646/an-invertebrate-sting-from-shrimp-activates-an-innate-immune-defense-against-bacterial-infection
#4
Haoyang Li, Sheng Wang, Kai Lǚ, Bin Yin, Bang Xiao, Sedong Li, Jianguo He, Chaozheng Li
It has been proposed that invertebrate stimulators of interferon genes (STINGs) do not take part in the innate immune response to infection. Herein, we identified a new STING homolog from pacific white shrimp Litopenaeus vannamei (LvSTING). Some amino acids crucial for recognizing cyclic dinucleotides in mammals are highly conserved in LvSTING. Moreover, LvSTING expression can be robustly induced by challenge with the Gram-negative bacteria Vibrio parahaemolyticus. Silencing of LvSTING contributes to decreased expression of the antimicrobial peptide PEN4 and renders shrimp more susceptible to V...
February 25, 2017: FEBS Letters
https://www.readbyqxmd.com/read/28236575/unravelling-endogenous-microrna-system-dysfunction-as-a-new-pathophysiological-mechanism-in-machado-joseph-disease
#5
Vitor Carmona, Janete Cunha-Santos, Isabel Onofre, Ana Teresa Simões, Udaya Vijayakumar, Beverly L Davidson, Luís Pereira de Almeida
Machado-Joseph disease (MJD) is a genetic neurodegenerative disease caused by an expanded polyglutamine tract within the protein ataxin-3 (ATXN3). Despite current efforts, MJD's mechanism of pathogenesis remains unclear and no disease-modifying treatment is available. Therefore, in this study, we investigated (1) the role of the 3' UTR of ATXN3, a putative microRNA (miRNA) target, (2) whether miRNA biogenesis and machinery are dysfunctional in MJD, and (3) which specific miRNAs target ATXN3-3' UTR and whether they can alleviate MJD neuropathology in vivo...
February 21, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28235637/inhibition-of-mir-92d-3p-enhances-inflammation-responses-in-genetically-improved-farmed-tilapia-gift-oreochromis-niloticus-with-streptococcus-iniae-infection-by-modulating-complement-c3
#6
Jun Qiang, Yi-Fan Tao, Jie He, Hong-Xia Li, Pao Xu, Jin-Wen Bao, Yi-Lan Sun
MicroRNAs (miRNAs) are small, non-coding RNAs that regulate target gene expression by binding to the 3'-untranslated regions (3'-UTRs) of their target mRNAs. The miR-92 family is an important miRNA family, which was discovered to be related to regulation of tumor proliferation, apoptosis, invasion, and metastasis. Inhibition of miR-92d-3p was found previously in head kidney of genetically improved farmed tilapia (GIFT, Oreochromis niloticus) exposed to Streptococcus iniae infection. In this study, we found that miR-92d-3p regulated complement C3 mRNA levels by binding to its 3'-UTR by 3'-UTR luciferase reporter assay, and reduced miR-92d-3p expression resulted in increased C3 mRNA levels...
February 21, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28231341/identification-of-the-er-resident-e3-ubiquitin-ligase-rnf145-as-a-novel-lxr-regulated-gene
#7
Emma C L Cook, Jessica K Nelson, Vincenzo Sorrentino, Duco Koenis, Martina Moeton, Saskia Scheij, Roelof Ottenhoff, Boris Bleijlevens, Anke Loregger, Noam Zelcer
Cellular cholesterol metabolism is subject to tight regulation to maintain adequate levels of this central lipid molecule. Herein, the sterol-responsive Liver X Receptors (LXRs) play an important role owing to their ability to reduce cellular cholesterol load. In this context, identifying the full set of LXR-regulated genes will contribute to our understanding of their role in cholesterol metabolism. Using global transcriptional analysis we report here the identification of RNF145 as an LXR-regulated target gene...
2017: PloS One
https://www.readbyqxmd.com/read/28222440/sumo-1-gene-silencing-inhibits-proliferation-and-promotes-apoptosis-of-human-gastric-cancer-sgc-7901-cells
#8
Lifang Jin, Kexin Shen, Tong Chen, Wei Yu, Huaiyu Zhang
BACKGROUND: It has been reported that blocking small ubiquitin-like modifier (SUMO) conjugation by silencing SUMO gene remarkably decreased tumor growth in vivo. However, few studies have examined the relationship between SUMO gene silencing and gastric cancer (GC). The study aims to explore the effects of SUMO-1 gene silencing on GC cell proliferation and apoptosis. METHODS: GC cells were cultured and divided into 5 groups: the blank group (without any transfection or treatment), the empty vector group (transfected with empty vector), the shRNA-SUMO-1-1 group (transfected with shRNA-SUMO-1-1 plasmid), the shRNA-SUMO-1-2 group (transfected with shRNA-SUMO-1-2 plasmid), and the shRNA-SUMO-1-3 group (transfected with shRNA-SUMO-1-3 plasmid)...
February 21, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28218746/early-transcriptional-and-epigenetic-regulation-of-cd8-t-cell-differentiation-revealed-by-single-cell-rna-sequencing
#9
Boyko Kakaradov, Janilyn Arsenio, Christella E Widjaja, Zhaoren He, Stefan Aigner, Patrick J Metz, Bingfei Yu, Ellen J Wehrens, Justine Lopez, Stephanie H Kim, Elina I Zuniga, Ananda W Goldrath, John T Chang, Gene W Yeo
During microbial infection, responding CD8(+) T lymphocytes differentiate into heterogeneous subsets that together provide immediate and durable protection. To elucidate the dynamic transcriptional changes that underlie this process, we applied a single-cell RNA-sequencing approach and analyzed individual CD8(+) T lymphocytes sequentially throughout the course of a viral infection in vivo. Our analyses revealed a striking transcriptional divergence among cells that had undergone their first division and identified previously unknown molecular determinants that controlled the fate specification of CD8(+) T lymphocytes...
February 20, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28218744/live-cell-imaging-to-compare-the-transfection-and-gene-silencing-efficiency-of-calcium-phosphate-nanoparticles-and-a-liposomal-transfection-agent
#10
S Chernousova, M Epple
The processing of DNA (for transfection) and siRNA (for gene silencing), introduced into HeLa cells by triple-shell calcium phosphate nanoparticles, was followed by live-cell imaging. For comparison, the commercial liposomal transfection agent Lipofectamine(TM) was used. The cells were incubated with these delivery systems, carrying either eGFP-encoding DNA or siRNA against eGFP. In the latter case, HeLa cells which stably expressed eGFP were used. The expression of eGFP started after 5 h in the case of nanoparticles and after 4 h in the case of Lipofectamine...
February 20, 2017: Gene Therapy
https://www.readbyqxmd.com/read/28215614/genome-characterization-infectivity-assays-of-in-vitro-and-in-vivo-infectious-transcripts-of-soybean-yellow-mottle-mosaic-virus-from-india-reveals-a-novel-short-mild-genotype
#11
Nagamani Sandra, A Abdul Kader Jailani, Rakesh Kumar Jain, Bikash Mandal
Nucleotide sequence of a distinct soybean yellow mottle mosaic virusisolate from Vignaradiata (mungbean isolate, SYMMV-Mb) from India was determined and compared with othermembers of the family Tombusviridae. The complete monopartite single-stranded RNA genome of SYMMV-Mb consisted of 3974nt with six putative open reading frames and includes 5' and 3' untranslated regions of 35 and 254nt, respectively. SYMMV-Mb genome shared 75% nt sequence identity at complete genome level and 67-92% identity at all ORFs level with SYMMV Korean and USA isolates (soybean isolates) followed by CPMoV, whereas it shared very low identity with other tombusviridae members (5-41%)...
February 17, 2017: Virus Research
https://www.readbyqxmd.com/read/28214826/emodin-increases-expression-of-insulin-like-growth-factor-binding-protein-1-through-activation-of-mek-erk-ampk%C3%AE-and-interaction-of-ppar%C3%AE-and-sp1-in-lung-cancer
#12
Qing Tang, JingJing Wu, Fang Zheng, Swei Sunny Hann, YuQing Chen
BACKGROUND: Emodin has anti-neoplastic activities on multiple tumors. However, the molecular mechanisms underlying this effect still remain to be fully understood. METHODS: Cell viability and cell cycle distribution were measured using 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assays and flow cytometry, respectively. Cell invasion and migration were examined by transwell invasion and wound healing assays. Western blot analysis was performed to examine the phosphorylation and protein expression of AMP-activated protein kinase alpha (AMPKα), extracellular signaling-regulated kinase 1/2 (ERK1/2), peroxisome proliferators-activated receptor gamma (PPARγ), insulin-like growth factor (IGF) binding protein 1 (IGFBP1) and the transcription factor Sp1...
January 26, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28211215/zkscan1-gene-and-its-related-circular-rna-circzkscan1-both-inhibit-hepatocellular-carcinoma-cell-growth-migration-and-invasion-but-through-different-signaling-pathways
#13
Zhicheng Yao, Jingyan Luo, Kunpeng Hu, Jizong Lin, He Huang, Qiangliang Wang, Peng Zhang, Zhiyong Xiong, Zejian Huang, Chonghua He, Bo Liu, Yang Yang
There is increasing evidence that circular RNAs (circRNAs) are involved in cancer development, but the regulation and function of human circRNAs remain largely unknown. In this study, we demonstrated that ZKSCAN1, a zinc finger family gene, is expressed in both linear and circular (circZKSCAN1) forms of RNA in human hepatocellular carcinoma (HCC) tissues and cell lines. Here, we analyzed a cohort of 102 patients and found that expression of both ZKSCAN1 mRNA and circZKSCAN1 was significantly lower (P<0.05) in the HCC samples compared with that in matched adjacent non-tumorous tissues by reverse transcription PCR (RT-PCR)...
February 16, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28210006/a-novel-lsd1-inhibitor-ncd38-ameliorates-mds-related-leukemia-with-complex-karyotype-by-attenuating-leukemia-programs-via-activating-super-enhancers
#14
N Sugino, M Kawahara, G Tatsumi, A Kanai, H Matsui, R Yamamoto, Y Nagai, S Fujii, Y Shimazu, M Hishizawa, T Inaba, A Andoh, T Suzuki, A Takaori-Kondo
Lysine-specific demethylase 1 (LSD1) regulates gene expression by affecting histone modifications and is a promising target for acute myeloid leukemia (AML) with specific genetic abnormalities. Novel LSD1 inhibitors, NCD25 and NCD38, inhibited growth of MLL-AF9 leukemia as well as erythroleukemia, megakaryoblastic leukemia and myelodysplastic syndromes (MDS) overt leukemia cells in the concentration range that normal hematopoiesis was spared. NCD25 and NCD38 invoked the myeloid development programs, hindered the MDS and AML oncogenic programs, and commonly upregulated 62 genes in several leukemia cells...
February 17, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28207859/differential-effects-of-silencing-crustacean-hyperglycemic-hormone-gene-expression-on-the-metabolic-profiles-of-the-muscle-and-hepatopancreas-in-the-crayfish-procambarus-clarkii
#15
Wenfeng Li, Kuo-Hsun Chiu, Yi-Chun Tien, Shih-Fu Tsai, Li-Jane Shih, Chien-Hsun Lee, Jean-Yves Toullec, Chi-Ying Lee
In order to functionally characterize the metabolic roles of crustacean hyperglycemic hormone (CHH), gene expression of CHH in the crayfish (Procambarus clarkii) was knocked down by in vivo injection of CHH double-stranded RNA (dsRNA), followed by metabolomic analysis of 2 CHH target tissues (the muscle and hepatopancreas) using nuclear magnetic resonance spectroscopy. Compared to the levels in untreated and saline-injected (SAI) animals, levels of CHH transcript, but not those of molt-inhibiting hormone (a CHH-family peptide), in the eyestalk ganglia of CHH dsRNA-injected (DSI) animals were significantly decreased at 24, 48, and 72 hour post injection (hpi), with concomitant changes in levels of CHH peptide in the sinus gland (a neurohemal organ) and hemolymph...
2017: PloS One
https://www.readbyqxmd.com/read/28207159/the-critical-role-of-the-znf217-oncogene-in-promoting-breast-cancer-metastasis-to-the-bone
#16
Aurélie Bellanger, Caterina F Donini, Julie A Vendrell, Jonathan Lavaud, Irma Machuca-Gayet, Maëva Ruel, Julien Vollaire, Evelyne Grisard, Balázs Győrffy, Ivan Bièche, Olivier Peyruchaud, Jean-Luc Coll, Isabelle Treilleux, Véronique Maguer-Satta, Véronique Josserand, Pascale A Cohen
Bone metastasis affects more than 70% of patients with advanced breast cancer. However, the molecular mechanisms underlying this process remain unclear. Based on the analysis of clinical datasets, and in vitro and in vivo experiments, we report that the ZNF217 oncogene is a crucial mediator and indicator of bone metastasis. Patients with high ZNF217 mRNA expression levels in primary breast tumours had a higher risk of developing bone metastases. MDA-MB-231 breast cancer cells stably transfected with ZNF217 (MDA-MB-231-ZNF217) displayed the dysregulated expression of a set of genes with bone homing and metastasis characteristics, which overlapped with two previously described "osteolytic bone metastasis" gene signatures, while also highlighting the bone morphogenetic protein (BMP) pathway...
February 16, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28198538/role-of-pin1-on-in-vivo-periodontal-tissue-and-in-vitro-cells
#17
K-H Park, E-H Cho, W-J Bae, H-S Kim, H-C Lim, Y-D Park, M-O Lee, E-S Cho, E-C Kim
BACKGROUND: Although expression of peptidyl-prolyl cis/trans isomerase NIMA-interacting 1 (PIN1) was reported in bone tissue, the precise role of PIN1 in periodontal tissue and cells remain unclear. MATERIAL & METHODS: To elucidate the roles of PIN1 in periodontal tissue, its expression in periodontal tissue and cells, and effects on in vitro 4 osteoblast differentiation and the underlying signaling mechanisms were evaluated. RESULTS: PIN1 was expressed in mouse periodontal tissues including periodontal ligament cells (PDLCs), cementoblasts and osteoblasts at the developing root formation stage (postnatal, PN14) and functional stage of tooth (PN28)...
February 15, 2017: Journal of Periodontal Research
https://www.readbyqxmd.com/read/28196596/chemosensitive-relapse-in-small-cell-lung-cancer-proceeds-through-an-ezh2-slfn11-axis
#18
Eric E Gardner, Benjamin H Lok, Valentina E Schneeberger, Patrice Desmeules, Linde A Miles, Paige K Arnold, Andy Ni, Inna Khodos, Elisa de Stanchina, Thuyen Nguyen, Julien Sage, John E Campbell, Scott Ribich, Natasha Rekhtman, Afshin Dowlati, Pierre P Massion, Charles M Rudin, John T Poirier
Small cell lung cancer is initially highly responsive to cisplatin and etoposide but in almost every case becomes rapidly chemoresistant, leading to death within 1 year. We modeled acquired chemoresistance in vivo using a series of patient-derived xenografts to generate paired chemosensitive and chemoresistant cancers. Multiple chemoresistant models demonstrated suppression of SLFN11, a factor implicated in DNA-damage repair deficiency. In vivo silencing of SLFN11 was associated with marked deposition of H3K27me3, a histone modification placed by EZH2, within the gene body of SLFN11, inducing local chromatin condensation and gene silencing...
February 13, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28194140/hiv-1-tat-and-viral-latency-what-we-can-learn-from-naturally-occurring-sequence-variations
#19
REVIEW
Doreen Kamori, Takamasa Ueno
Despite the effective use of antiretroviral therapy, the remainder of a latently HIV-1-infected reservoir mainly in the resting memory CD4(+) T lymphocyte subset has provided a great setback toward viral eradication. While host transcriptional silencing machinery is thought to play a dominant role in HIV-1 latency, HIV-1 protein such as Tat, may affect both the establishment and the reversal of latency. Indeed, mutational studies have demonstrated that insufficient Tat transactivation activity can result in impaired transcription of viral genes and the establishment of latency in cell culture experiments...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28193906/cbx3-promotes-colon-cancer-cell-proliferation-by-cdk6-kinase-independent-function-during-cell-cycle
#20
Yao Fan, Haiping Li, Xiaolong Liang, Zheng Xiang
Heterochromatin protein 1γ (CBX3) links histone methylation marks to transcriptional silence, DNA repair and RNA splicing, but a role for CBX3 in cancer remains largely unknown. In this study, we show that CBX3 in colon cancer cells promotes the progression of the cell cycle and proliferation in vitro and in vivo. Cell cycle (G1 phase to S phase) related gene CDK6 and p21 were further identified as targets of CBX3. In addition, we found that enhancing CDK6 suppresses cell proliferation by upregulating inhibitor p21 in the absence of CBX3, and this function is independent of the kinase activity of CDK6...
February 10, 2017: Oncotarget
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