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In vivo gene silencing

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https://www.readbyqxmd.com/read/29778567/emp3-which-is-regulated-by-mir-663a-suppresses-gallbladder-cancer-progression-via-interference-with-the-mapk-erk-pathway
#1
Qiang Ma, Yijian Zhang, Haibin Liang, Fei Zhang, Fatao Liu, Shili Chen, Yunping Hu, Lin Jiang, Yajuan Hao, Maolan Li, Yingbin Liu
Gallbladder cancer (GBC) is the most common malignancy of the biliary tract and its molecular pathogenesis is poorly understood. Aberrant expression of epithelial membrane protein-3 (EMP3) was reported in different kinds of cancers. Our study aimed to explore the elusive functional roles and the underlying molecular mechanisms of EMP3 with respect to GBC progression. The results showed that human GBC tissues exhibited decreased levels of EMP3 compared with non-malignant tissues. Kaplan-Meier analysis indicated that low expression of EMP3 was associated with poor prognosis of GBC patients...
May 17, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29778422/sp1-induced-upregulation-of-lncrna-pandar-predicts-adverse-phenotypes-in-retinoblastoma-and-regulates-cell-growth-and-apoptosis-in-vitro-and-in-vivo
#2
Lijie Sheng, Jing Wu, Xuewu Gong, Duo Dong, Xiaoxue Sun
Retinoblastoma (RB) is an intraocular malignancy for children and has a high mortality rate. Long non-coding RNAs (lncRNAs) are emerging as gene regulators and biomarkers in various malignancies. PANDAR is a novel cancer-related lncRNA that dysregulated in several types of cancers. However, its clinical value and potential effects on RB remains unclear. RT-qPCR was used to assess the relative expression of PANDAR in RB tissues and cells. Additionally, chromatin immunoprecipitation (ChIP) and luciferase reporter assays were performed to investigate whether SP1 could bind to the promoter region of PANDAR and activate its transcription...
May 17, 2018: Gene
https://www.readbyqxmd.com/read/29777785/psmd2-regulates-breast-cancer-cell-proliferation-and-cell-cycle-progression-by-modulating-p21-and-p27-proteasomal-degradation
#3
Yunhai Li, Jing Huang, Beilei Zeng, Dejuan Yang, Jiazheng Sun, Xuedong Yin, Mengqi Lu, Zhu Qiu, Weiyan Peng, Tingxiu Xiang, Hongzhong Li, Guosheng Ren
Alterations in the ubiquitin-proteasome system (UPS) and UPS-associated proteins have been implicated in the development of many human malignancies. In this study, we investigated the expression profiles of 797 UPS-related genes using HiSeq data from The Cancer Genome Atlas and identified that PSMD2 was markedly upregulated in breast cancer. High PSMD2 expression was significantly correlated with poor prognosis. Gene set enrichment analysis revealed that transcriptome signatures involving proliferation, cell cycle, and apoptosis were critically enriched in specimens with elevated PSMD2...
May 16, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29773900/c5a-induces-a549-cell-proliferation-of-non-small-cell-lung-cancer-via-gdf15-gene-activation-mediated-by-gcn5-dependent-klf5-acetylation
#4
Chenhui Zhao, Yongting Li, Wen Qiu, Fengxia He, Weiming Zhang, Dan Zhao, Zhiwei Zhang, Erbao Zhang, Pei Ma, Yiqian Liu, Ling Ma, Fengming Yang, Yingwei Wang, Yongqian Shu
Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, and multiple evidence has confirmed that C5a production is elevated in NSCLC microenvironment. Although NSCLC cell proliferation induced by C5a has been reported, the involved mechanism has not been elucidated. In this study, we examined the proliferation-related genes (i.e., KLF5, GCN5, and GDF15) and C5a receptor (C5aR) expression in tumor tissues as well as C5a concentration in plasma of NSCLC patients, and then determined the roles of KLF5, GCN5, and GDF15 in C5a-triggered NSCLC cell proliferation and the related mechanism both in vitro and in vivo...
May 18, 2018: Oncogene
https://www.readbyqxmd.com/read/29772233/roseburia-intestinalis-derived-flagellin-is-a-negative-regulator-of-intestinal-inflammation
#5
Yongsheng Quan, Kerui Song, Yan Zhang, Changxin Zhu, Zhaohua Shen, Shuai Wu, Weiwei Luo, Bei Tan, Zhenyu Yang, Xiaoyan Wang
Our previous study showed that the Roseburia intestinalis (R. intestinalis), one of the dominant intestinal bacterial microbiota, was significantly decreased in Crohn's disease patients and protected colon epithelial cells from inflammatory damage. However, the roles of lncRNAs in R. intestinalis flagellin-mediated anti-inflammation remain unclear. In this study, we investigate global lncRNA expression profiles using microarray analysis of ulcerative colitis samples from DSS/Flagellin-challenged mice and identified a Flagellin-induced upregulated lncRNA (HIF1A-AS2)...
May 14, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29771428/ampk-regulates-energy-metabolism-through-the-sirt1-signaling-pathway-to-improve-myocardial-hypertrophy
#6
H-W Dong, L-F Zhang, S-L Bao
OBJECTIVE: We investigated the correlations of adenosine monophosphate-activated protein kinase (AMPK), Silence information regulator 1 (SIRT1) and energy metabolism with myocardial hypertrophy. MATERIALS AND METHODS: Myocardial hypertrophy experimental model was established via transverse aortic constriction (TAC)-induced myocardial hypertrophy and phenylephrine (PE)-induced hypertrophic myocardial cell culture. After activation of AMPK, the messenger ribonucleic acid (mRNA) expressions in myocardial tissue- and myocardial cell hypertrophy-related genes, atrial natriuretic peptide (ANP) and β-myosin heavy chain (β-MHC), were detected...
May 2018: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/29770869/curcumin-inhibits-autocrine-growth-hormone-mediated-invasion-and-metastasis-by-targeting-nf-%C3%AE%C2%BAb-signaling-and-polyamine-metabolism-in-breast-cancer-cells
#7
Ajda Coker-Gurkan, Merve Celik, Merve Ugur, Elif-Damla Arisan, Pinar Obakan-Yerlikaya, Zeynep Begum Durdu, Narcin Palavan-Unsal
Curcumin is assumed to be a plant-derived therapeutic drug that triggers apoptotic cell death in vitro and in vivo by affecting different molecular targets such as NF-κB. Phase I/II trial of curcumin alone or with chemotherapeutic drugs has been accomplished in pancreatic, colon, prostate and breast cancer cases. Recently, autocrine growth hormone (GH) signaling-induced cell growth, metastasis and drug resistance have been demonstrated in breast cancer. In this study, our aim was to investigate the potential therapeutic effect of curcumin by evaluating the molecular machinery of curcumin-triggered apoptotic cell death via focusing on NF-κB signaling and polyamine (PA) metabolism in autocrine GH-expressing MCF-7, MDA-MB-453 and MDA-MB-231 breast cancer cells...
May 16, 2018: Amino Acids
https://www.readbyqxmd.com/read/29769402/gtsf-1-is-required-for-formation-of-a-functional-rna-dependent-rna-polymerase-complex-in-caenorhabditis-elegans
#8
Miguel Vasconcelos Almeida, Sabrina Dietz, Stefan Redl, Emil Karaulanov, Andrea Hildebrandt, Christian Renz, Helle D Ulrich, Julian König, Falk Butter, René F Ketting
Argonaute proteins and their associated small RNAs (sRNAs) are evolutionarily conserved regulators of gene expression. Gametocyte-specific factor 1 (Gtsf1) proteins, characterized by two tandem CHHC zinc fingers and an unstructured C-terminal tail, are conserved in animals and have been shown to interact with Piwi clade Argonautes, thereby assisting their activity. We identified the Caenorhabditis elegans Gtsf1 homolog, named it gtsf-1 and characterized it in the context of the sRNA pathways of C. elegans We report that GTSF-1 is not required for Piwi-mediated gene silencing...
May 16, 2018: EMBO Journal
https://www.readbyqxmd.com/read/29769196/an-in-vivo-screen-identifies-pygo2-as-a-driver-for-metastatic-prostate-cancer
#9
Xin Lu, Xiaolu Pan, Chang-Jiun Wu, Di Zhao, Shan Feng, Yong Zang, Rumi Lee, Sunada Khadka, Samirkumar B Amin, Eun-Jung Jin, Xiaoying Shang, Pingna Deng, Yanting Luo, William R Morgenlander, Jacqueline Weinrich, Xuemin Lu, Shan Jiang, Qing Chang, Nora M Navone, Patricia Troncoso, Ronald A DePinho, Y Alan Wang
Advanced prostate cancer displays conspicuous chromosomal instability and rampant copy number aberrations, yet the identity of functional drivers resident in many amplicons remain elusive. Here, we implemented a functional genomics approach to identify new oncogenes involved in prostate cancer progression. Through integrated analyses of focal amplicons in large prostate cancer genomic and transcriptomic datasets as well as genes upregulated in metastasis, 276 putative oncogenes were enlisted into an in vivo gain-of-function tumorigenesis screen...
May 16, 2018: Cancer Research
https://www.readbyqxmd.com/read/29767944/theranostic-niosomes-for-efficient-sirna-microrna-delivery-and-activatable-near-infrared-fluorescent-tracking-of-stem-cells
#10
Chuanxu Yang, Shan Gao, Ping Song, Frederik Dagnaes-Hansen, Maria Jakobsen, Jørgen Kjems
RNA interference (RNAi) mediated gene regulation in stem cells offers great potential in regenerative medicine. In this study, we developed a theranostic platform for efficient delivery of small RNAs (siRNA/miRNA) to human mesenchymal stem cells (hMSCs) to promote differentiation, and meanwhile, to specifically label the transfected cells for in vivo tracking purpose. We encapsulated indocyanine green (ICG) in a nonionic surfactant vesicle, termed "niosome", that is mainly composed of a nonionic surfactant sorbitan monooleate (Span 80) and a cationic lipid 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP)...
May 16, 2018: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/29767259/silencing-of-mir%C3%A2-155-suppresses-inflammatory-responses-in-psoriasis-through-inflammasome-nlrp3-regulation
#11
Quan Luo, Jingxin Zeng, Wei Li, Ling Lin, Xin Zhou, Xin Tian, Weiyu Liu, Lidan Zhang, Xibao Zhang
Psoriasis is a dermatosis with the major clinical symptoms of scale, erythema and itching, and it has a long disease course. In addition, it is easily recurrent and refractory, greatly affecting the physical and mental health of patients. In the present study, it was hypothesized that the function of miR‑155 increases psoriasis‑induced inflammation and that its expression may be dependent on inflammasome activation. miR‑155 expression was examined by gene chip array and quantitative polymerase chain reaction analysis...
May 14, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29761849/muc1-c-drives-myeloid-leukaemogenesis-and-resistance-to-treatment-by-a-survivin-mediated-mechanism
#12
Dina Stroopinsky, Hasan Rajabi, Myrna Nahas, Jacalyn Rosenblatt, Maryam Rahimian, Athalia Pyzer, Ashujit Tagde, Akriti Kharbanda, Salvia Jain, Turner Kufe, Rebecca K Leaf, Eleni Anastasiadou, Michal Bar-Natan, Shira Orr, Maxwell D Coll, Kristen Palmer, Adam Ephraim, Leandra Cole, Abigail Washington, Donald Kufe, David Avigan
Acute myeloid leukaemia (AML) is an aggressive haematological malignancy with an unmet need for improved therapies. Responses to standard cytotoxic therapy in AML are often transient because of the emergence of chemotherapy-resistant disease. The MUC1-C oncoprotein governs critical pathways of tumorigenesis, including self-renewal and survival, and is aberrantly expressed in AML blasts and leukaemia stem cells (LSCs). However, a role for MUC1-C in linking leukaemogenesis and resistance to treatment has not been described...
May 15, 2018: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29759938/differentiation-therapy-by-epigenetic-reconditioning-exerts-antitumor-effects-on-liver-cancer-cells
#13
Luc Gailhouste, Lee Chuen Liew, Ken Yasukawa, Izuho Hatada, Yasuhito Tanaka, Hitoshi Nakagama, Takahiro Ochiya
Primary liver tumors are mainly represented by hepatocellular carcinoma (HCC), one of the most aggressive and resistant forms of cancer. Liver tumorigenesis is characterized by an accumulation of epigenetic abnormalities, leading to gene extinction and loss of hepatocyte differentiation. The aim of this work was to investigate the feasibility of converting liver cancer cells toward a less aggressive and differentiated phenotype using a process called epigenetic reconditioning. Here, we showed that an epigenetic regimen with non-cytotoxic doses of the demethylating compound 5-azacytidine (5-AZA) promoted an anti-cancer response by inhibiting HCC cell tumorigenicity...
April 26, 2018: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/29759079/s-allylcysteine-suppresses-ovarian-cancer-cell-proliferation-by-dna-methylation-through-dnmt1
#14
Yasi Xu, Dan Su, Lucheng Zhu, Shirong Zhang, Shenglin Ma, Kan Wu, Qiang Yuan, Nengming Lin
BACKGROUND: The anti-tumor effects of S-allylcysteine (SAC), a water-soluble garlic derivative, on human ovarian cancer cells have been previous studied in vitro and in vivo models but the precise epigenetic molecular mechanisms are still unclear. This study aimed to investigate the epigenetic mechanism of SAC. METHODS: Human epithelial ovarian cancer cell line A2780 was selected. Cell proliferation and cell cycle was analyzed. DNA methylation, DNA methyltransferase (DNMT) activity, tumor suppressor gene expressions, as well as protein expression were analyzed...
May 14, 2018: Journal of Ovarian Research
https://www.readbyqxmd.com/read/29758199/pafah1b2-is-a-hif1a-target-gene-and-promotes-metastasis-in-pancreatic-cancer
#15
Can Ma, Yan Guo, Yan Zhang, Aixia Duo, Yitao Jia, Ci Liu, Binghui Li
Platelet-activating factor acetylhydrolase IB subunit beta (PAFAH1B2) plays important roles in inflammation and anaphylaxis. However, its primary function in pancreatic cancer remains unclear. In the current study, we report that PAFAH1B2 is overexpressed in pancreatic ductal adenocarcinoma (PDAC) and correlated inversely with patient survival. PAFAH1B2 overexpression induced epithelial-mesenchymal transition (EMT), migration and invasion in vitro and metastasis in vivo. Conversely, silencing PAFAH1B2 inhibited these aggressive phenotypes...
May 11, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29758178/lin28a-regulates-neurogliogenesis-in-mammalian-retina-through-the-igf-signaling
#16
Xiaohuan Xia, Pooja Teotia, Iqbal Ahmad
In the developing central nervous system (CNS) the majority of neurons are born before the generation of glia. Emerging evidence implicates heterochronic gene, Lin28 in the temporal switch between two distinct lineages. However, the respective contributions of Lin28a and Lin28b in neurogliogenesis remain poorly understood. Here, we have examined the relative involvement of Lin28a and Lin28b in mammalian retina, a simple and accessible CNS model where neurogliogenic decision largely occurs postnatally. Examination of Lin28a/b involvement during late histogenesis by the perturbation of function approaches revealed that while Lin28b did not influence differentiation in general Lin28a facilitated and antagonized the generation of neurons and glia, respectively...
May 11, 2018: Developmental Biology
https://www.readbyqxmd.com/read/29757189/notch-effector-csl-promotes-squamous-cell-carcinoma-by-repressing-histone-demethylase-kdm6b
#17
Dania Al Labban, Seung-Hee Jo, Paola Ostano, Chiara Saglietti, Massimo Bongiovanni, Renato Panizzon, G Paolo Dotto
Notch 1/2 genes play tumor-suppressing functions in squamous cell carcinoma (SCC), a very common malignancy in skin and internal organs. In contrast with Notch, we show that the transcription factor CSL (also known as RBP-Jκ), a key effector of canonical Notch signaling endowed with intrinsic transcription-repressive functions, plays a tumor-promoting function in SCC development. Expression of this gene decreased in upper epidermal layers and human keratinocytes (HKCs) undergoing differentiation, while it increased in premalignant and malignant SCC lesions from skin, head/neck, and lung...
May 14, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29753027/jmjd3-inhibition-protects-against-isoproterenol-induced-cardiac-hypertrophy-by-suppressing-%C3%AE-mhc-expression
#18
Zhen Guo, Jing Lu, Jingyan Li, Panxia Wang, Zhenzhen Li, Yao Zhong, Kaiteng Guo, Junjian Wang, Jiantao Ye, Peiqing Liu
Jumonji domain-containing protein D3 (JMJD3), a histone 3 lysine 27 (H3K27) demethylase, has been extensively studied for their participation in development, cellular physiology and a variety of diseases. However, its potential roles in cardiovascular system remain unknown. In this study, we found that JMJD3 played a pivotal role in the process of cardiac hypertrophy. JMJD3 expression was elevated by isoproterenol (ISO) stimuli both in vitro and in vivo. Overexpression of wild-type JMJD3, but not the demethylase-defective mutant, promoted cardiomyocyte hypertrophy, as implied by increased cardiomyocyte surface area and the expression of hypertrophy marker genes...
May 9, 2018: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/29752937/lncrna-thor-promotes-human-renal-cell-carcinoma-cell-growth
#19
Xue-Ting Ye, Hang Huang, Wei-Ping Huang, Wei-Lie Hu
BACKGROUND: Recent studies have characterized a novel but extremely conserved long non-coding RNA (LncRNA) THOR. THOR directly associates with insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) to promote mRNA stabilization of key pro-cancerous genes. RESULTS: Here, we show that THOR is expressed in human renal cell carcinoma (RCC) tissues and established/primary human RCC cells. It was not detected in normal renal tissues nor in HK-2 and primary human renal epithelial cells...
May 9, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29752722/a-new-cancer-immunotherapy-via-simultaneous-dc-mobilization-and-dc-targeted-ido-gene-silencing-using-an-immune-stimulatory-nanosystem
#20
Yujuan Zhang, Jiamin Fu, Yanmei Shi, Shanshan Peng, Ying Cai, Xuelin Zhan, Na Song, Yanling Liu, Zhigang Wang, Yanrong Yu, Yifan Wang, Qiaofa Shi, Yingyuan Fu, Keng Yuan, Nanjin Zhou, Rakesh Joshi, Thomas E Ichim, Weiping Min
The activity of negative immune regulatory molecules, such as indoleamine 2,3-oxygenase (IDO), significantly attenuates DC (Dendritic cells)-mediated immunotherapy. We have previously reported that knockdown of IDO using siRNA can reinstall anti-tumor immunity. However, a DC-targeted siRNA delivery system for in vivo mobilized DCs remains to be developed, while gene silencing in mobilized DCs for cancer immunotherapy has never been explored. In this study, we developed a novel DC-targeted siRNA delivery system, man-GNR-siIDO, using as a nanocarrier of siRNA specific for IDO (siIDO) and mannose (man) as a guide molecule for targeting DCs...
May 11, 2018: International Journal of Cancer. Journal International du Cancer
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