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In vivo gene silencing

Yu Cai, Pu Yan, Ge Zhang, Wenqi Yang, Haiping Wang, Xiaohu Cheng
OBJECTIVE: Colorectal cancer (CRC) is the 3rd most common cancer worldwide. Recently, long non-coding RNAs (lncRNAs) were found to be critical modulators in the CRC progression. The aim of this study is to investigate the potential roles of lncRNA P73 antisense RNA 1T (TP73-AS1) in CRC development and progression. METHODS: Quantitative real-time PCR (qRT-PCR) was performed to determine relevant gene expression levels; western blot was performed to determine protein expression levels; CCK-8, colony formation, wound healing and Transwell invasion assays were used to determined CRC cell proliferation, migration and invasion; in vivo tumor growth was assessed in xenograft mice model...
June 29, 2018: Cancer Biomarkers: Section A of Disease Markers
Chen Gu, Jillian Ramos, Ulrike Begley, Peter C Dedon, Dragony Fu, Thomas J Begley
The human transfer RNA methyltransferase 9-like gene (TRM9L, also known as KIAA1456) encodes a negative regulator of tumor growth that is frequently silenced in many forms of cancer. While TRM9L can inhibit tumor cell growth in vivo, the molecular mechanisms underlying the tumor inhibition activity of TRM9L are unknown. We show that oxidative stress induces the rapid and dose-dependent phosphorylation of TRM9L within an intrinsically disordered domain that is necessary for tumor growth suppression. Multiple serine residues are hyperphosphorylated in response to oxidative stress...
July 2018: Science Advances
Beibei Chen, Qingfang Zhao, Lulu Guan, Huifang Lv, Liangyu Bie, Jinxi Huang, Xiao-Bing Chen
Long non-coding RNAs (lncRNAs) have been illustrated to function as important regulators in carcinogenesis and cancer progression. However, the roles of lncRNA NNT-AS1 in gastric cancer remain unclear. In the present study, we investigate the biological role of NNT-AS1 in gastric cancer tumorigenesis. Results revealed that NNT-AS1 expression level was significantly up-regulated in GC tissue and cell lines compared with adjacent normal tissue and normal cell lines. The ectopic overexpression of NNT-AS1 indicated the poor prognosis of GC patients...
July 14, 2018: Journal of Cellular and Molecular Medicine
Wei Deng, Wenjie Chen, Sandhya Clement, Anna Guller, Zhenjun Zhao, Alexander Engel, Ewa M Goldys
Liposomes have been well established as an effective drug delivery system, due to simplicity of their preparation and unique characteristics. However conventional liposomes are unsuitable for the on-demand content release, which limits their therapeutic utility. Here we report X-ray-triggerable liposomes incorporating gold nanoparticles and photosensitizer verteporfin. The 6 MeV X-ray radiation induces verteporfin to produce singlet oxygen, which destabilises the liposomal membrane and causes the release of cargos from the liposomal cavity...
July 13, 2018: Nature Communications
Xiao-Fang Wei, You-Fan Feng, Qiao-Lin Chen, Qi-Ke Zhang
Background: As a disease of hematopoietic stem cell, chronic myeloid leukemia (CML) possesses unique biological and clinical features. However, the biologic mechanism underlying its development remains poorly understood. Thus, the objective of the present study is to discuss the effect of cytidine deaminase (CDA) gene silencing on the apoptosis and proliferation of CML K562 cells. Methods: CDA mRNA expression was detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and enzymatic activity of CDA was measured by a nuclide liquid scintillation method...
2018: Cancer Cell International
Fan Wu, Pin Gao, Wei Wu, Zaozao Wang, Jie Yang, Jiabo Di, Beihai Jiang, Xiangqian Su
BACKGROUND: Serine/threonine protein kinase 25 (STK25) is critical in regulating whole-body glucose and insulin homeostasis and the accumulation of ectopic lipids. The Warburg effect, also known as aerobic glycolysis, is an essential metabolic characteristic of cancer cells. However, the effects of STK25 on aerobic glycolysis of cancer cells remain unexplored. The aim of this study is to investigate the role of STK25 in colorectal cancer (CRC) and to elucidate the underlying mechanisms...
July 11, 2018: Journal of Experimental & Clinical Cancer Research: CR
F Liu, W B Xie, L Y Zhou, Y H Liu, W Y Fang, K T Yao
Objective: To observe the effect of knockdown A20 gene expression on the proliferation, invasion and metastasis of human nasopharyngeal carcinoma cell in vivo and in vivo . Methods: Human nasopharyngeal carcinoma cell 5-8F-H3 was transfected with A20-specific shRNA Tet-on inducible plasmid vectors, and A20 silenced cells were screened by Puromycin. Quantitative RT-PCR and Western blot analysis were used to detect the mRNA level and protein of A20. The cell proliferation was detected by cell counting kit-8 (CCK8) and plate colony formation assays...
June 26, 2018: Zhonghua Yi Xue za Zhi [Chinese medical journal]
Ying-Qin Li, Fa-Huan Song, Ke Zhong, Guang-Yin Yu, Prince Last Mudenda Zilundu, Ying-Ying Zhou, Rao Fu, Ying Tang, Ze-Min Ling, Xiaoying Xu, Li-Hua Zhou
Brachial plexus injury is a common clinical peripheral nerve trauma. A series of genes in motoneurons were activated in the corresponding segments of the spinal cord after brachial plexus roots axotomy. The spatial and temporal expression of these genes directly affects the speed of motoneuron axon regeneration and precise target organ reinnervation. In a previous study, we observed the overexpression of c-Jun in motoneurons of the spinal cord ventral horn after brachial plexus injury in rats. However, the relevance of c-Jun expression with respect to the fate of axotomy-induced branchial plexus injury in adult mice remains unknown...
July 10, 2018: Journal of Molecular Neuroscience: MN
Zeki Ilkan, Benjamin Strauss, Chiara Campana, Fadi G Akar
Ischemia-reperfusion (I/R) injury causes dynamic changes in electrophysiological properties that promote the incidence of post-ischemic arrhythmias. High-resolution optical action potential mapping allows for a quantitative assessment of the electrophysiological substrate at a cellular resolution within the intact heart, which is critical for elucidation of arrhythmia mechanisms. We and others have found that pharmacological inhibition of the translocator protein (TSPO) is highly effective against postischemic arrhythmias...
2018: Methods in Molecular Biology
Qi Sun, Xiaoli Wang, Chunying Cui, Jing Li, Yifan Wang
Background: Graphene oxide (GO) has attracted intensive interest in biological and medical fields in recent years due to its unique physical, chemical, and biological properties. In our previous work, we proved that GO could deliver small interfering RNA (siRNA) into cells and downregulate the expression of the desired gene. Methods: This study investigated the potential of a modified GO nanocarrier for co-delivery of siRNA and doxorubicin (DOX) for enhanced cancer therapy...
2018: International Journal of Nanomedicine
Hayfa Medfai, Alia Khalil, Alexandre Rousseau, Vincent Nuyens, Martina Paumann-Page, Benjamin Sevcnikar, Paul G Furtmüller, Christian Obinger, Nicole Moguilevsky, Olivier Peulen, Michael Herfs, Vincent Castronovo, Mohamed Amri, Pierre Van Antwerpen, Luc Vanhamme, Karim Zouaoui Boudjeltia
Aims: The term angiogenesis refers to sprouting of new blood vessels from pre-existing ones. The angiogenic process involves cell migration and tubulogenesis requiring interaction between endothelial cells and the extracellular matrix. Human peroxidasin 1 (hsPxd01) is a multidomain heme peroxidase found embedded in the basement membranes. As it promotes the stabilization of extracellular matrix, we investigated its possible role in angiogenesis both in vitro and in vivo. Methods and Results: We analyzed the effects of peroxidasin 1 gene silencing and supplementation by recombinant hsPxd01 in TeloHAEC endothelial cells on cell migration, tubulogenesis in matrigel and intracellular signal transduction as assessed by kinase phosphorylation and expression of pro-angiogenic genes as measured by qRT-PCR...
July 4, 2018: Cardiovascular Research
Payton D Stevens, Yang-An Wen, Xiaopeng Xiong, Yekaterina Y Zaytseva, Austin T Li, Chi Wang, Ashley T Stevens, Trevor N Farmer, Tong Gan, Heidi L Weiss, Masaki Inagaki, Sylvie Marchetto, Jean-Paul Borg, Tianyan Gao
Erbin belongs to the LAP (leucine-rich repeat and PDZ domain) family of scaffolding proteins that plays important roles in orchestrating cell signaling. Here we show that Erbin functions as a tumor suppressor in colorectal cancer (CRC). Analysis of Erbin expression in CRC patient specimens revealed that Erbin was downregulated at both mRNA and protein levels in tumor tissues. Knockdown of Erbin disrupted epithelial cell polarity and increased cell proliferation in 3D culture. In addition, silencing Erbin resulted in increased amplitude and duration of signaling through Akt and RAS/RAF pathways...
July 6, 2018: Cancer Research
Lin Chen, Jizhen Wei, Chen Liu, Wanna Zhang, Bingjie Wang, LinLin Niu, Gemei Liang
A pyramid strategy combining the crystal (Cry) 1A and 2A toxins in Bacillus thuringiensis (Bt) crops are active against many species of insects and nematode larvae. It has been widely used to delay pest adaption to genetically modified plants and broaden the insecticidal spectrum in many countries. Unfortunately, Cry2A can also bind with the specific receptor proteins of Cry1A. ATP-binding cassette (ABC) transporters can interact with Cry1A toxins as receptors in the insect midgut, and ABC transporter mutations result in resistance to Bt proteins...
2018: Frontiers in Physiology
Yuting Li, Yuhua Sun, Min Cai, Huanhuan Zhang, Nannan Gao, Huiwei Huang, Shusen Cui, Dengbing Yao
Wallerian degeneration (WD) is associated with changes in the expression levels of a large number of genes. However, the effects of these up- or down-regulated genes are poorly understood. We have reported some key factors that are differentially regulated during WD in our previous research. Here, we explored the roles of Fas ligand gene (Faslg) in WD after rat sciatic nerve injury. The data showed that Faslg was up-regulated in injured nerves. Expression changed of Faslg in Schwann cells (SCs) resulted in alterations in the release of related factors...
2018: Frontiers in Molecular Neuroscience
Yang Yu, Mingjiong Zhang, Ni Wang, Quanpeng Li, Jian Yang, Shuai Yan, Xuezhi He, Guozhong Ji, Lin Miao
Cholangiocarcinoma (CCA) is the as the most frequently observed biliary tract malignancy, which has low survival rate in addition to constrained treatment options; nevertheless, the fundamental molecular phenomenon underlying malignant progression of CCA is quite ambiguous. Recently long non-coding RNAs (lncRNAs) have been found to have significant regulatory functions in several human cancers. Herein, we have figured out that lncRNA SNHG1, with substantially enhanced expression in CCA, is capable of acting as the oncogenic molecule of CCA...
July 3, 2018: Cell Death & Disease
Quan Sun, Wei Zhang, Lei Wang, Fei Guo, Dongjian Song, Qian Zhang, Da Zhang, Yingzhong Fan, Jiaxiang Wang
OBJECTIVE: Our study aimed to explore the relationship between CD36 methylation and the development of lung cancer and investigate the effect of combine treatment of Decitabine and Chidamide in lung cancer. METHODS: The differentially expression genes in tumor samples and normal samples were determined by microarray analysis. Weighted gene co-expression network analysis (WGCNA) was utilized to analyze gene expression data of lung cancer and the hub genes were screened in the modules...
June 30, 2018: Gene
Ningfang Ma, Xiaohui Zhao, Tian Xie, Ting Dai, Wenhui Zhao, Jing Li, Rui Xu, Chao Jiang, Peiqiong Li, Junyao Deng, Xiaobo Su
Calcineurin B homologous protein isoform 2 (CHP2), an essential cofactor for Na+/H+ exchanger isoform 1 (NHE1), is identified to be expressed in various malignant cell lines. However, the clinical significance and biological role of CHP2 in breast cancer remain to be established. Here, CHP2 was markedly overexpressed in breast cancer cells and clinical tumor specimens. Immunohistochemical (IHC) analysis revealed that the expression of CHP2 was significantly correlated with patients' clinicopathologic characteristics like clinical stage, and breast cancer patients with high CHP2 expression had shorter overall survival compared to patients with low CHP2 expression...
July 2, 2018: Molecular Cancer Research: MCR
So Young Kim, MiNa Hong, Seung-Ho Heo, Sojung Park, Taeg Kyu Kwon, Young Hoon Sung, Yumin Oh, Seulki Lee, Gwan-Su Yi, Inki Kim
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been characterized as an anti-cancer therapeutic agent with prominent cancer cell selectivity over normal cells. However, breast cancer cells are generally resistant to TRAIL, thus limiting its therapeutic potential. In this study, we found that BIX-01294, a selective inhibitor of euchromatin histone methyltransferase 2/G9a, is a strong TRAIL sensitizer in breast cancer cells. The combination of BIX-01294 and TRAIL decreased cell viability and led to an increase in the annexin V/propidium iodide-positive cell population, DNA fragmentation, and caspase activation...
July 2, 2018: Molecular Carcinogenesis
Shwathy Ramesan, Amgad R Rezk, Chaitali Dekiwadia, Christina Cortez-Jugo, Leslie Y Yeo
Recent breakthroughs in gene editing have necessitated practical ex vivo methods to rapidly and efficiently re-engineer patient-harvested cells. Many physical membrane-disruption or pore-forming techniques for intracellular delivery, however, result in poor cell viability, while most carrier-mediated techniques suffer from suboptimal endosomal escape and hence cytoplasmic or nuclear targeting. In this work, we show that short exposure of cells to high frequency (>10 MHz) acoustic excitation facilitates temporal reorganisation of the lipid structure in the cell membrane that enhances translocation of gold nanoparticles and therapeutic molecules into the cell within just ten minutes...
July 2, 2018: Nanoscale
Hongliang Zuo, Jia Yuan, Linwei Yang, Jiefu Zheng, Shaoping Weng, Jianguo He, Xiaopeng Xu
The thioredoxin system plays essential roles in maintenance and regulation of the redox state of cysteine residues in cellular proteins. The thioredoxin-related protein of 14 kDa (TRP14) is an important member of the TRX superfamily which acts on various substrate proteins, some of which are not overlapped with those of thioredoxin. The knowledge on the function of TRP14 in invertebrates is limited to date. In this study, a TRP14 gene was identified from Pacific white shrimp Litopenaeus vannamei (LvTRP14) and its role in immune responses was investigated...
June 28, 2018: Fish & Shellfish Immunology
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