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https://www.readbyqxmd.com/read/28435523/discovery-of-1-2-3-triazolo-4-5-d-pyrimidine-derivatives-as-novel-lsd1-inhibitors
#1
Zhong-Hua Li, Xue-Qi Liu, Peng-Fei Geng, Feng-Zhi Suo, Jin-Lian Ma, Bin Yu, Tao-Qian Zhao, Zhao-Qing Zhou, Chen-Xi Huang, Yi-Chao Zheng, Hong-Min Liu
Lysine specific demethylase 1 (LSD1) plays a pivotal role in regulating the lysine methylation. The aberrant overexpression of LSD1 has been reported to be involved in the progression of certain human malignant tumors. Abrogation of LSD1 with RNAi or small molecule inhibitors may lead to the inhibition of cancer proliferation and migration. Herein, a series of [1,2,3]triazolo[4,5-d]pyrimidine derivatives were synthesized and evaluated for their LSD1 inhibitory effects. The structure-activity relationship studies (SARs) were conducted by exploring three regions of this scaffold, leading to the discovery of compound 27 as potent LSD1 inhibitor (IC50 = 0...
April 13, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28435471/nucleolin-targeted-extracellular-vesicles-as-a-versatile-platform-for-biologics-delivery-to-breast-cancer
#2
Yayu Wang, Xiaojia Chen, Baoqing Tian, Jiafan Liu, Li Yang, Lilan Zeng, Tianfen Chen, An Hong, Xiaogang Wang
Small interfering RNAs (siRNA)/microRNAs (miRNA) have promising therapeutic potential, yet their clinical application has been hampered by the lack of appropriate delivery systems. Herein, we employed extracellular vesicles (EVs) as a targeted delivery system for small RNAs. EVs are cell-derived small vesicles that participate in cell-to-cell communication for protein and RNA delivery. We used the aptamer AS1411-modified EVs for targeted delivery of siRNA/microRNA to breast cancer tissues. Tumor targeting was facilitated via AS1411 binding to nucleolin, which is highly expressed on the surface membrane of breast cancer cells...
2017: Theranostics
https://www.readbyqxmd.com/read/28430789/mir-9-3p-augments-apoptosis-induced-by-h2o2-through-down-regulation-of-herpud1-in-glioma
#3
Ling Yang, Yongping Mu, Hongwei Cui, Yabing Liang, Xiulan Su
MicroRNAs are short, single-stranded non-coding RNA molecules that function as regulators of tumor progression in various cancers, including glioma. The present study sought to investigate the biological functions of miR-9-3p in glioma progression. The results of a microRNA microarray indicated that microRNA-9-3p (miR-9-3p, miR-9*) is down-regulated in high-grade (grades III and IV) gliomas compared with non-tumor tissues. These results were confirmed with real-time PCR. The miR-9-3p expression level was associated with age and tumor grade...
2017: PloS One
https://www.readbyqxmd.com/read/28428090/preparation-and-characterization-of-lipid-nanoparticle-pdna-complexes-for-stat3-downregulation-and-overcoming-chemotherapy-resistance-in-lung-cancer-cells
#4
Mustafa Kotmakçı, Vildan Bozok Çetintaş, A Gülten Kantarcı
Developments in the field of molecular oncology have revealed that resistance to chemotherapeutics is acqured through several mechanisms including overexpression of common oncogenic proteins. Signal Transducer and Activator of Transcription 3 (STAT3) is one of these oncogenes that is overexpressed in many cancer types. RNA interference (RNAi) is proven powerful tool for downregulating STAT3, allowing re-sensitization of resistant cancer cells. However, delivery of RNA interference-mediating molecules for STAT3 downregulation in lung cancer cells is limited to a small number of studies most of which employ commercially available transfection kits...
April 17, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28423924/advances-in-sirna-delivery-in-cancer-therapy
#5
Aishwarya Singh, Piyush Trivedi, Narendra Kumar Jain
RNA interference (RNAi)-based therapeutic approaches are under vibrant scrutinisation to seek cancer cure. siRNA suppress expression of the carcinogenic genes by targeting the mRNA expression. However, in vivo systemic siRNA therapy is hampered by the barriers such as poor cellular uptake, instability under physiological conditions, off-target effects and possible immunogenicity. To overcome these challenges, systemic siRNA therapy warrants the development of clinically suitable, safe, and effective drug delivery systems...
April 19, 2017: Artificial Cells, Nanomedicine, and Biotechnology
https://www.readbyqxmd.com/read/28423617/the-e3-ubiquitin-ligase-nedd4-is-translationally-upregulated-and-facilitates-pancreatic-cancer
#6
Min Weng, Zhu-Lin Luo, Xiao-Ling Wu, Wei-Zheng Zeng
AIM: To determine the regulation and function of the neural precursor cell expressed developmentally down regulated protein 4 (NEDD4) in PDAC and to determine its dependency on phosphatase and tensin homolog (PTEN) and PI3K/AKT signaling. METHODS: We investigated the expression of NEDD4 and the tumor suppressor PTEN in normal immortalized human pancreatic duct epithelial cell line and pancreatic adenocarcinoma (PDAC) cell lines. We further evaluated whether RNAi-mediated depletion of NEDD4 can attenuate PDAC cell proliferation and migration...
March 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423353/silencing-prdm14-expression-by-an-innovative-rnai-therapy-inhibits-stemness-tumorigenicity-and-metastasis-of-breast-cancer
#7
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/28420995/quantum-dots-sirna-nanoplexes-for-gene-silencing-in-central-nervous-system-tumor-cells
#8
Guimiao Lin, Ting Chen, Jinyun Zou, Yucheng Wang, Xiaomei Wang, Jiefeng Li, Qijun Huang, Zicai Fu, Yingying Zhao, Marie Chia-Mi Lin, Gaixia Xu, Ken-Tye Yong
RNA interfering (RNAi) using short interfering RNA (siRNA) is becoming a promising approach for cancer gene therapy. However, owing to the lack of safe and efficient carriers, the application of RNAi for clinical use is still very limited. In this study, we have developed cadmium sulphoselenide/Zinc sulfide quantum dots (CdSSe/ZnS QDs)-based nanocarriers for in vitro gene delivery. These CdSSe/ZnS QDs are functionalized with polyethyleneimine (PEI) to form stable nanoplex (QD-PEI) and subsequently they are used for siRNA loading which specially targets human telomerase reverse transcriptase (TERT)...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28415695/detection-of-copb2-as-a-kras-synthetic-lethal-partner-through-integration-of-functional-genomics-screens
#9
Eleni G Christodoulou, Hai Yang, Franziska Lademann, Christian Pilarsky, Andreas Beyer, Michael Schroeder
Mutated KRAS plays an important role in many cancers. Although targeting KRAS directly is difficult, indirect inactivation via synthetic lethal partners (SLPs) is promising. Yet to date, there are no SLPs from high-throughput RNAi screening, which are supported by multiple screens. Here, we address this problem by aggregating and ranking data over three independent high-throughput screens. We integrate rankings by minimizing the displacement and by considering established methods such as RIGER and RSA.Our meta analysis reveals COPB2 as a potential SLP of KRAS with good support from all three screens...
March 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28414551/long-noncoding-rna-mnx1-as1-knockdown-inhibits-cell-proliferation-and-migration-in-ovarian-cancer
#10
Yan Lv, Huan Li, Fengling Li, Peishu Liu, Xinrui Zhao
Long noncoding RNAs (lncRNAs) have recently emerged as pivotal regulators that govern fundamental biological processes and disease pathogenesis. LncRNA MNX1-AS1 has been reported to promote cell proliferation and invasion in gallbladder cancer, but its biological role and regulatory mechanism in ovarian cancer are poorly defined. In this study, it was found that higher expression of lncRNA MNX1-AS1 is closely associated with International Federation of Gynecology and Obstetrics stage and lymphatic metastasis in ovarian cancer patients...
April 2017: Cancer Biotherapy & Radiopharmaceuticals
https://www.readbyqxmd.com/read/28412671/role-of-sdf-1-and-cxcr4-in-the-proliferation-migration-and-invasion-of-cervical-cancer
#11
Chen Wang, Hailing Cheng, Yanyun Li
This study was to investigate the role of stromal cell-derived factor 1 (SDF-1) and its corresponding receptor CXCR4 in the proliferation, migration and invasion of cervical cancer HeLa cells. CXCR4 expression in HeLa cells was measured by flow cytometry and Western Blot. Role of SDF-1 and CXCR4 in the HeLa cells proliferation was measured by MTT. Role of SDF-1 and CXCR4 in the migration and invasion of HeLa cell was measured by Boyden chamber. High expression of CXCR4 was observed on the surface of HeLa cells...
November 2016: Pakistan Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28411182/pegylation-rate-influences-peptide-based-nanoparticles-mediated-sirna-delivery-in-vitro-and-in-vivo
#12
Gudrun Aldrian, Anaïs Vaissière, Karidia Konate, Quentin Seisel, Eric Vivès, Frédéric Fernandez, Véronique Viguier, Coralie Genevois, Franck Couillaud, Héléne Démèné, Dina Aggad, Aurélie Covinhes, Stéphanie Barrère-Lemaire, Sébastien Deshayes, Prisca Boisguerin
Small interfering RNAs (siRNAs) present a strong therapeutic potential because of their ability to inhibit the expression of any desired protein. Recently, we developed the retro-inverso amphipathic RICK peptide as novel non-covalent siRNA carrier. This peptide is able to form nanoparticles (NPs) by self-assembling with the siRNA resulting in the fully siRNA protection based on its protease resistant peptide sequence. With regard to an in vivo application, we investigated here the influence of the polyethylene glycol (PEG) grafting to RICK NPs on their in vitro and in vivo siRNA delivery properties...
April 11, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28404940/rnai-mediated-inhibition-of-lgr5-leads-to-decreased-angiogenesis-in-gastric-cancer
#13
Hong-Qing Xi, Ke-Cheng Zhang, Ji-Yang Li, Jian-Xin Cui, Yun-He Gao, Bo Wei, Dongsheng Huang, Lin Chen
Leucine-rich repeat-containing G protein-coupled receptor 5 (Lgr5) is a novel gastric cancer marker. However, it is unclear whether it can play roles in tumor angiogenesis. In this study, we aim to investigate the role of Lgr5 on gastric cancer angiogenesis. Lgr5, VEGF expression levels and microvessel density (MVD) were detected in tumor tissue. Then, Lgr5 mRNA was downregulated by small interference RNA technique. Western blotting and real-time quantitative PCR (qRT-PCR) were performed to detect the expression of Lgr5 and VEGF protein and mRNA in Lgr5 siRNA-transfected gastric cancer cells...
February 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28400477/il-4-primes-the-dynamics-of-breast-cancer-progression-via-dusp4-inhibition
#14
Miriam Gaggianesi, Alice Turdo, Aurora Chinnici, Elisa Lipari, Tiziana Apuzzo, Antonina Benfante, Isabella Sperduti, Simone Di Franco, Serena Meraviglia, Elena Lo Presti, Francesco Dieli, Valentina Caputo, Gabriella Militello, Salvatore Vieni, Giorgio Stassi, Matilde Todaro
The tumor microenvironment supplies pro-inflammatory cytokines favoring a permissive milieu for cancer cell growth and invasive behavior. Here we show how breast cancer progression is facilitated by IL-4 secreted by adipose tissue and estrogen receptor-positive and triple-negative breast cancer cell types. Blocking autocrine and paracrine IL-4 signaling with the IL-4Rα antagonist IL-4DM compromised breast cancer cell proliferation, invasion and tumor growth by downregulating MAPK pathway activity. IL-4DM reduced numbers of CD44+/CD24- cancer stem-like cells and elevated expression of the dual specificity phosphatase DUSP4 by inhibiting NF-kB...
April 11, 2017: Cancer Research
https://www.readbyqxmd.com/read/28393234/downregulation-of-tnfaip2-suppresses-proliferation-and-metastasis-in-esophageal-squamous-cell-carcinoma-through-activation-of-the-wnt-%C3%AE-catenin-signaling-pathway
#15
Yunbo Xie, Bin Wang
Tumor necrosis factor-α (TNF-α) plays a pivotal role in malignant tumor formation in the tumor microenvironment. To investigate the role of TNF-α in esophageal squamous cell carcinoma (ESCC), we assessed expression profiles of the downstream gene TNF-α-induced protein 2 (TNFAIP2), which e previously unknown in ESCC. TNFAIP2 mRNA and protein expression levels were examined by qRT-PCR and immunohistochemical analysis in 24 fresh and 55 paraffin‑embedded specimens, respectively. The results demonstrated that TNFAIP2 mRNA and protein levels were overexpressed in tumor cells, and TNFAIP2 overexpression was significantly associated with T stage (p=0...
April 5, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28392163/current-progress-in-non-viral-rnai-based-delivery-strategies-to-lymphocytes
#16
REVIEW
Shoshy Mizrahy, Inbal Hazan-Halevy, Niels Dammes, Dalit Landesman-Milo, Dan Peer
RNAi-based therapy holds great promise, as it can be utilized for the treatment of multiple conditions in an accurate manner via sequence-specific manipulation of gene expression. To date, RNAi therapeutics have advanced into clinical trials for liver diseases and solid tumors; however, delivery of RNAi to leukocytes in general and to lymphocytes in particular remains a challenge. Lymphocytes are notoriously hard to transduce with RNAi payloads and are disseminated throughout the body, often located in deep tissues; therefore, developing an efficient systemic delivery system directed to lymphocytes is not a trivial task...
April 6, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28389707/the-race-of-10-synthetic-rnai-based-drugs-to-the-pharmaceutical-market
#17
REVIEW
Ricardo Titze-de-Almeida, Catherine David, Simoneide Souza Titze-de-Almeida
Ten years after Fire and Melo's Nobel Prize for discovery of gene silencing by double-stranded RNA, a remarkable progress was achieved in RNA interference (RNAi). Changes in the chemical structure of synthetic oligonucleotides make them more stable and specific, and new delivery strategies became progressively available. The attention of pharmaceutical industry rapidly turned to RNAi, as an opportunity to explore new drug targets. This review addresses nine small-interfering RNAs (siRNAs) and one unique microRNA (miRNA) inhibitor, which entered the phase 2-3 clinical trials...
April 7, 2017: Pharmaceutical Research
https://www.readbyqxmd.com/read/28386355/foxc1-promotes-proliferation-and-epithelial-mesenchymal-transition-in-cervical-carcinoma-through-the-pi3k-akt-signal-pathway
#18
Liu Huang, Zheng Huang, Yi Fan, Langchi He, Ming Ye, Kun Shi, Bing Ji, Jiezhen Huang, Yibin Wang, Qiufen Li
Recently, Forkhead box C1 (FOXC1) has been identified to play important roles in human cancers. However, the clinical significance and biological role of FOXC1 in cervical cancer remains unclear. Here, we showed that FOXC1 was frequently overexpressed in cervical cancer versus adjacent non-tumor tissues. Overexpression of FOXC1 was significantly correlated with tumor stage (P=0.011), tumor size (P=0.034), stromal invasion (P=0.001), and lymph nodes metastasis (P=0.008). Survival analysis further suggested that high FOXC1 expression was significantly correlated with poor overall survival (P=0...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28386261/rna-interference-induced-innate-immunity-off-target-effect-or-immune-adjuvant
#19
REVIEW
Zhongji Meng, Mengji Lu
RNA interference (RNAi) is a natural cellular mechanism that inhibits gene expression in a sequence-specific manner. In the last decade, RNAi has become a cornerstone in basic biological systems research and drug development efforts. The RNAi-based manipulation of mammalian cells facilitates target identification and validation; assists in identifying human disease etiologies; and expedites the development of treatments for infectious diseases, cancer, and other conditions. Several RNAi-based approaches are currently undergoing assessment in phase I and II clinical trials...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28385785/imatinib-and-spironolactone-suppress-hepcidin-expression
#20
Katarzyna Mleczko-Sanecka, Ana Rita da Silva, Debora Call, Joana Neves, Nikolai Schmeer, Georg Damm, Daniel Seehofer, Martina U Muckenthaler
Disorders of iron metabolism are largely attributed to an excessive or insufficient expression of hepcidin, the master regulator of systemic iron homeostasis. Here, we investigated whether drugs targeting genetic regulators of hepcidin can affect iron homeostasis. We focused our efforts on drugs approved for clinical use to enable repositioning strategies and/or to reveal iron-related side effects of widely prescribed therapeutics. To identify hepcidin-modulating therapeutics, we reevaluated data generated by a genome-wide RNAi screen for hepcidin regulators...
April 6, 2017: Haematologica
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