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Rnai cancer

Beth K Neilsen, Binita Chakraborty, Jamie L McCall, Danielle E Frodyma, Richard L Sleightholm, Kurt W Fisher, Robert E Lewis
BACKGROUND: KMT2/MLL proteins are commonly overexpressed or mutated in cancer and have been shown to support cancer maintenance. These proteins are responsible for methylating histone 3 at lysine 4 and promoting transcription and DNA synthesis; however, they are inactive outside of a multi-protein complex that requires WDR5. WDR5 has been implicated in cancer for its role in the COMPASS complex and its interaction with Myc; however, the role of WDR5 in colon cancer has not yet been elucidated...
June 20, 2018: BMC Cancer
Smaranda Buduru, Alina-Andreea Zimta, Cristina Ciocan, Cornelia Braicu, Diana Dudea, Alexandra Iulia Irimie, Ioana Berindan-Neagoe
Over the last few decades, the incidence of oral cancer has gradually increased, due to the negative influence of environmental factors and also abnormalities within the genome. The main issues in oral cancer treatment consist in surpassing resistance and recurrence. However, continuous discovery of altered signaling pathways in these tumors provides valuable information for the identification of novel gene candidates targeted in personalized therapy. RNA interference (RNAi) is a natural mechanism that involves small interfering RNA (siRNA); this can be exploited in biomedical research by using natural or synthetic constructs for activation of the mechanism...
2018: International Journal of Nanomedicine
Donald Bastin, Amelia S Aitken, Adrian Pelin, Larissa A Pikor, Mathieu J F Crupi, Michael S Huh, Marie-Claude Bourgeois-Daigneault, John C Bell, Carolina S Ilkow
Antiviral responses are barriers that must be overcome for efficacy of oncolytic virotherapy. In mammalian cells, antiviral responses involve the interferon pathway, a protein-signaling cascade that alerts the immune system and limits virus propagation. Tumour-specific defects in interferon signaling enhance viral infection and responses to oncolytic virotherapy, but many human cancers are still refractory to oncolytic viruses. Given that invertebrates, fungi and plants rely on RNA interference pathways for antiviral protection, we investigated the potential involvement of this alternative antiviral mechanism in cancer cells...
June 19, 2018: Journal for Immunotherapy of Cancer
Jiali Zhang, Zuo Wang, Siwei Zhang, Yanxun Chen, Xuexue Xiong, Xiaojuan Li, Nicholas K Tonks, Gaofeng Fan
A critical aspect of understanding the regulation of signal transduction is not only to identify the protein-protein interactions that govern assembly of signaling pathways, but also to understand how those pathways are regulated in time and space. In this report, we have applied both gain-of-function and loss-of-function analyses to assess the role of the non-receptor protein tyrosine kinase FER in activation of the HGF Receptor protein tyrosine kinase MET. Overexpression of FER led to direct phosphorylation of several signaling sites in MET, including Tyr1349, but not the activation loop residues Tyr1234/5; in contrast, suppression of FER by RNAi revealed that phosphorylation of both a C-terminal signaling site (Tyr1349) and the activation loop (Tyr1234/5) were influenced by the function of this kinase...
June 16, 2018: Cellular Signalling
Abdelmeniem El-Bakoush, Olumayokun A Olajide
Formononetin is a bioactive non-steroidal polyphenol found in a variety of plants. In this study we evaluated the effects of formononetin on neuroinflammation in LPS-stimulated BV2 microglia. Results showed that formononetin significantly reduced the production of TNF-α, IL-6 and IL-1β, nitrite and PGE2 , as well as protein levels of iNOS and COX-2. Reporter gene assays showed that formononetin produced inhibition of NF-κB luciferase activity in HEK293 cells stimulated with TNF-α. Immunoblotting experiments revealed an inhibition of IKKα phosphorylation, with the resultant attenuation of phosphorylation and degradation of IκBα following LPS stimulation...
June 15, 2018: International Immunopharmacology
Xiaoxia Huang, Jinyuan Li, Jin Xie, Yang Li, Yan Gao, Xiaohui Li, Xueqin Xu, Ruoshi Shi, Wanjun Yao, Changbin Ke
Activation of spinal cord microglia is crucial for the development of bone cancer pain (BCP). The essential signal between neuronal excitability and microglial activation is not fully understood. In the present study, carcinoma implantation into tibia was used to induce BCP and RNAi-lentivirus was injected into spinal cord to knock down C1, C2 or C3 of complement cascade. We showed that C1, C2 and C3 co-localized in the same neurons and increased in cancer-bearing rats along with microglial activation. Knocked down of C1, C2 or C3 inhibited microglial activation and prevented the development of cancer-induced bone pain...
June 14, 2018: Brain Research
Pratik Kadekar, Rita Chaouni, Emily Clark, Anna Kazanets, Richard Roy
BACKGROUND: Caenorhabditis elegans can endure long periods of environmental stress by altering their development to execute a quiescent state called "dauer". Previous work has implicated LKB1 - the causative gene in the autosomal dominant, cancer pre-disposing disease called Peutz-Jeghers Syndrome (PJS), and its downstream target AMPK, in the establishment of germline stem cell (GSC) quiescence during the dauer stage. Loss of function mutations in both LKB1/par-4 and AMPK/aak(0) result in untimely GSC proliferation during the onset of the dauer stage, although the molecular mechanism through which these factors regulate quiescence remains unclear...
June 15, 2018: BMC Genomics
Peng Liu, Shengfeng Wang, Xuanjun Liu, Jinsong Ding, Wenhu Zhou
Cisplatin (CisPt) is one of the most effective antitumor drugs against a wide range of solid cancers, and recent studies have indicated that combination of CisPt and RNA interference (RNAi) agents would effectively enhance therapeutic index, while the development of simple yet robust dual-delivery systems still remains a challenge. Here, we demonstrated that platinated graphene oxide is an excellent platform to achieve such goal. Nano-Graphene oxide (NGO) was easily platinated by CisPt, and the resulting CisPt/NGO was characterized by several aspects...
June 12, 2018: European Journal of Pharmaceutical Sciences
Konstantin Stoletov, Lian Willetts, Robert J Paproski, David J Bond, Srijan Raha, Juan Jovel, Benjamin Adam, Amy E Robertson, Francis Wong, Emma Woolner, Deborah L Sosnowski, Tarek A Bismar, Gane Ka-Shu Wong, Andries Zijlstra, John D Lewis
Metastasis is the most lethal aspect of cancer, yet current therapeutic strategies do not target its key rate-limiting steps. We have previously shown that the entry of cancer cells into the blood stream, or intravasation, is highly dependent upon in vivo cancer cell motility, making it an attractive therapeutic target. To systemically identify genes required for tumor cell motility in an in vivo tumor microenvironment, we established a novel quantitative in vivo screening platform based on intravital imaging of human cancer metastasis in ex ovo avian embryos...
June 14, 2018: Nature Communications
Ying Ji, Jinquan Jiang, Lihua Huang, Wei Feng, Zhang Zhang, Longyu Jin, Xiaowei Xing
Lung cancer is the most common cause of cancer‑related deaths, and early diagnosis and targeted therapy are extremely important in the treatment of this disease. Sperm‑associated antigen 4 (SPAG4) was recently found to be a novel cancer biomarker. In the present study, the expression of SPAG4 was revealed to be high in lung adenocarcinoma tissues as determined by western blotting and immunohistochemistry. SPAG4 knockdown by RNAi efficiently reduced the migration of the lung cancer A549 cells in vitro...
June 4, 2018: Oncology Reports
Taylor C Brown, Timothy D Murtha, Jill C Rubinstein, Reju Korah, Tobias Carling
BACKGROUND: Altered expression of Solute Carrier Family 12 Member 7 (SLC12A7) is implicated to promote malignant behavior in multiple cancer types through an incompletely understood mechanism. Recent studies have shown recurrent gene amplifications and overexpression of SLC12A7 in adrenocortical carcinoma (ACC). The potential mechanistic effect(s) of SLC12A7 amplifications in portending an aggressive behavior in ACC has not been previously studied and is investigated here using two established ACC cell lines, SW-13 and NCI-H295R...
June 8, 2018: Cell Communication and Signaling: CCS
Xue Hou, Run Gong, Jianhua Zhan, Ting Zhou, Yuxiang Ma, Yuanyuan Zhao, Yaxiong Zhang, Gang Chen, Zhonghan Zhang, Shuxiang Ma, Xi Chen, Fangfang Gao, Shaodong Hong, Fan Luo, Wenfeng Fang, Yunpeng Yang, Yan Huang, Likun Chen, Haoxian Yang, Li Zhang
BACKGROUND: Histone acetyltransferase p300 is a crucial transcriptional coactivator and has been implicated as a poor prognostic factor in human cancers. However, little is known about the substantial functions and mechanisms of p300 in NSCLC proliferation and distant metastasis. METHODS: We constructed p300 down-regulated and up-regulated cell lines through RNAi and recombinant plasmid transfection. Cell Counting Kit-8 assays were used to test the cell proliferation and confirmed by colony formation assays...
June 7, 2018: BMC Cancer
Heike Miess, Beatrice Dankworth, Arvin M Gouw, Mathias Rosenfeldt, Werner Schmitz, Ming Jiang, Becky Saunders, Michael Howell, Julian Downward, Dean W Felsher, Barrie Peck, Almut Schulze
Metabolic reprogramming is a prominent feature of clear cell renal cell carcinoma (ccRCC). Here we investigated metabolic dependencies in a panel of ccRCC cell lines using nutrient depletion, functional RNAi screening and inhibitor treatment. We found that ccRCC cells are highly sensitive to the depletion of glutamine or cystine, two amino acids required for glutathione (GSH) synthesis. Moreover, silencing of enzymes of the GSH biosynthesis pathway or glutathione peroxidases, which depend on GSH for the removal of cellular hydroperoxides, selectively reduced viability of ccRCC cells but did not affect the growth of non-malignant renal epithelial cells...
June 5, 2018: Oncogene
Md Emranul Karim, Kyi Kyi Tha, Iekhsan Othman, Mohammad Borhan Uddin, Ezharul Hoque Chowdhury
RNA Interference (RNAi) has brought revolutionary transformations in cancer management in the past two decades. RNAi-based therapeutics including siRNA and shRNA have immense scope to silence the expression of mutant cancer genes specifically in a therapeutic context. Although tremendous progress has been made to establish catalytic RNA as a new class of biologics for cancer management, a lot of extracellular and intracellular barriers still pose a long-lasting challenge on the way to clinical approval. A series of chemically suitable, safe and effective viral and non-viral carriers have emerged to overcome physiological barriers and ensure targeted delivery of RNAi...
May 26, 2018: Pharmaceutics
Theresia Zuleger, Julia Heinzelbecker, Zsuzsanna Takacs, Catherine Hunter, Jakob Voelkl, Florian Lang, Tassula Proikas-Cezanne
Background/Aims: As autophagy is linked to several pathological conditions, like cancer and neurodegenerative diseases, it is crucial to understand its regulatory signaling network. In this study, we investigated the role of the serum- and glucocorticoid-induced protein kinase 1 (SGK1) in the control of autophagy. Methods: To measure autophagic activity in vivo , we quantified the abundance of the autophagy conjugates LC3-PE (phosphatidylethanolamine) and ATG12-ATG5 in tissue extracts of SGK1 wild-type ( Sgk1 +/+ ) and knockout ( Sgk1 -/- ) mice that were either fed or starved for 24 h prior sacrifice...
2018: Oxidative Medicine and Cellular Longevity
Ke-Wen Zhou, Kun Jiang, Weizhi Zhu, Guobin Weng
The aim of the present study was to investigate the expression of cold-inducible RNA-binding protein (CIRP) in renal cell carcinoma (RCC) and to determine the effects of downregulation of CIRP on cell proliferation and chemosensitivity to gemcitabine. The expression of CIRP was detected by western blot analysis, quantitative polymerase chain reaction and immunohistochemistry (IHC) in 17 RCC and peri-cancerous tissue samples. Subsequently, the RCC 786-0 cell line was selected in order to investigate the function of CIRP using RNA interference (RNAi) technology, which was able to inhibit the expression of CIRP in vitro ...
May 2018: Oncology Letters
Chunyan Hou, Hu Bai, Zhaojie Wang, Yuanhao Qiu, Li-Li Kong, Feifei Sun, Dongdong Wang, Hong Yin, Xiaoli Zhang, Haibo Mu, Jinyou Duan
Accompanied by overproduction of oxidants and reduction of pH, inflammation is closely related to many diseases such as cancer, atherosclerosis, and asthma. Besides chemotherapeutic agents, the potential regulative role of autophagy in inflammation is being actively investigated. RNA interference (RNAi)-based gene therapy is widely explored for clinical therapy but seriously restricted by lack of suitable carriers. In this study, we synthesized a hyaluronan-based ROS-sensitive polymer which was expected to release loaded chemical drugs in inflammatory environment and further developed a stable and nontoxic co-delivery nanosystem of siRNA targeting autophagy suppressive gene and chemotherapeutic agents...
September 1, 2018: Carbohydrate Polymers
Qiuling Dong, Huaqing Zhang, Yue Han, Aouameur Djamila, Hao Cheng, Zhiyuan Tang, Jianping Zhou, Yang Ding
Metastatic cancer is difficult to defeat with current treatments due to lack of etiological therapeutics and efficient delivery platforms. Employing tumor microenvironment in programming intelligent nanosystems has attracted considerable attention for combinative antitumor therapy. Herein, we proposed a core-shell based drug depot consisting of micellar core and crosslinked-gel shell for site-specific shuttling of paclitaxel (PTX) and KIAA1199 specific shRNA (shKIAA). Poly (e-caprolactone) were grafted with branched polyethylenimine (PEI-PCL) as micellar core, into which hydrophobic PTX was embedded; while shKIAA, a reliable RNAi regimen for metastatic cell inhibition was condensed with PEI through electrostatic interaction; and then photo-crosslinked hyaluronic acid (m-HA) was further coated as shell...
May 24, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
Aaron D Springer, Steven F Dowdy
Short-interfering RNA (siRNA)-induced RNAi responses have great potential to treat a wide variety of human diseases from cancer to pandemic viral outbreaks to Parkinson's Disease. However, before siRNAs can become drugs, they must overcome a billion years of evolutionary defenses designed to keep invading RNAs on the outside cells from getting to the inside of cells. Not surprisingly, significant effort has been placed in developing a wide array of delivery technologies. Foremost of these has been the development of N-acetylgalactosamine (GalNAc) siRNA conjugates for delivery to liver...
May 24, 2018: Nucleic Acid Therapeutics
Marcel Klingenberg, Matthias Groß, Ashish Goyal, Maria Polycarpou-Schwarz, Thilo Miersch, Anne-Sophie Ernst, Jörg Leupold, Nitin Patil, Uwe Warnken, Heike Allgayer, Thomas Longerich, Peter Schirmacher, Michael Boutros, Sven Diederichs
The identification of viability-associated long non-coding RNAs (lncRNA) might be a promising rationale for new therapeutic approaches in liver cancer. Here, we applied the first RNAi screening approach in hepatocellular carcinoma (HCC) cell lines to find viability-associated lncRNAs. Among the multiple identified lncRNAs with a significant impact on HCC cell viability, we selected CASC9 (Cancer Susceptibility 9) due to the strength of its phenotype, expression, and upregulation in HCC versus normal liver. CASC9 regulated viability across multiple HCC cell lines as shown by CRISPR interference, single siRNA- and siPOOL-mediated depletion of CASC9...
May 23, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
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