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In vivo gene silencing

Maruthibabu Paidikondala, Ganesh N Nawale, Oommen P Varghese
Small interfering RNAs (siRNAs) are powerful tools for post-transcriptional gene silencing which offers enormous opportunities for tissue engineering applications. However, poor serum stability, inefficient intracellular delivery, and inevitable toxicity of transfection reagents are the key barriers for their clinical translation. Thus innovative strategies that allow safe and efficient intracellular delivery of the nucleic acid drugs at the desired site is urgently needed for a smooth clinical translation of therapeutically appealing siRNA-based technology...
January 14, 2019: Biomacromolecules
Shi Chen, Jiang-Zhi Chen, Jia-Qiang Zhang, Hui-Xing Chen, Fu-Nan Qiu, Mao-Lin Yan, Yi-Feng Tian, Cheng-Hong Peng, Bai-Yong Shen, Yan-Ling Chen, Yao-Dong Wang
Pancreatic cancer (PC) represents a relatively rare but severe malignancy worldwide. Accumulated studies have emphasized the potential of long noncoding RNA (lncRNA) as therapeutic strategies for several human cancers. Thus, we aimed to investigate whether a novel non-coding RNA regulatory circuitry involved in PC. Aberrantly expressed lncRNAs and mRNA were screened out of microarray database. Following the determination of RNA expression, PANC-1 and BxPC-3 PC cells were adopted, after which the expression of miR-330-5p, PAX8 and LINC00958 were subsequently altered...
January 9, 2019: Cancer Letters
Wei Cai, Yong Xu, Wenshan Zuo, Zhen Su
MiR-542-3p and its target gene integrin linked kinase ( ILK ) in human osteosarcoma together with the differentially expressed genes from osteosarcoma tissues was analyzed through bioinformatics analysis in this study. Real time quantitative polymerase chain reaction (qRT-PCR) and western blot showed that the miR-542-3p expression decreased while the ILK expression increased in the osteosarcoma tissues. The overexpressed miR-542-3p or silenced ILK restrained cell invasion, proliferation and migration and arrested cell cycle, facilitated cell apoptosis in U-2OS and 143B cells...
January 11, 2019: Aging
Yi Sang, Longhua Sun, Yuanzhong Wu, Wenxin Yuan, Yanyan Liu, Si-Wei Li
Plakoglobin is a tumor suppressor gene in lung cancer; however, the mechanism by which it is downregulated in lung cancer is largely unknown. The aim of the present study was to investigate whether histone deacetylases (HDACs) regulate plakoglobin expression in lung cancer. The effects of overexpression or knockdown of HDAC7 on plakoglobin were determined using stably transfected lung cancer cell lines. Chromatin immunoprecipitation assays were performed to elucidate the mechanisms underlying the HDAC7‑induced suppression of plakoglobin...
January 9, 2019: International Journal of Oncology
Huaping Tang, Weihong Lv, Wenxin Sun, Qiaojie Bi, Yueqin Hao
MicroRNAs (miRNAs) are short non‑coding RNAs, which generally regulate gene expression at the post‑transcriptional level. Dysregulation of miRNAs has been reported in numerous cancer types, including lung cancer. In the present study, the role of miR‑505 in non‑small cell lung cancer (NSCLC) cells was investigated. miR‑505 served a tumor suppressor role in NSCLC cells. By reverse transcriptase‑quantitative polymerase chain reaction detection, it was demonstrated that miR‑505 was downregulated in NSCLC tissues and cell lines, which is negatively associated with large tumor size, Tumor‑Node‑Metastasis stage and distant metastasis in patients with NSCLC...
December 31, 2018: International Journal of Molecular Medicine
Li-Ming Gao, Yue Zheng, Ping Wang, Lei Zheng, Wen-Li Zhang, Ya Di, Lan-Lan Chen, Xiao-Bo Yin, Qi Tian, Shan-Shan Shi, Shu-Feng Xu
The involvement of several microRNAs (miRs) in the initiation and development of tumor through the suppression of the target gene expression has been highlighted. The aberrant expression of microRNA-181d-5p (miR-181d-5p) and cyclin-dependent kinase inhibitor 3 (CDKN3) in non-small-cell lung cancer (NSCLC) was then screened by microarray analysis, In the present study, we performed a series of in vivo and in vitro experiments for the purpose of investigating their role in NSCLC and the underlying mechanism. There was a high expression of CDKN3 while miR-181d-5p was down-regulated in NSCLC...
January 10, 2019: American Journal of Physiology. Lung Cellular and Molecular Physiology
Moshe Lapidot, Uri Barash, Israel Vlodavsky, Harvey Pass
Malignant mesothelioma is a highly aggressive form of cancer with poor prognosis due to lack of markers for early diagnosis and resistance to conventional therapies. Heparanase, the sole heparan sulfate (HS) degrading endoglycosidase, regulates multiple biological activities that enhance tumor growth, metastasis, angiogenesis, and inflammation. Heparanase accomplishes this by degrading HS and thereby facilitating cell invasion and regulating the bioavailability of heparin-binding proteins. Applying pre-clinical and clinical models of human mesothelioma and potent inhibitors of heparanase enzymatic activity (PG545, Defibrotide) we investigated the significance of heparanase in the pathogenesis of mesothelioma...
December 7, 2018: Oncotarget
Hao Peng, Jian Zhang, Pan-Pan Zhang, Lei Chen, Ling-Long Tang, Xiao-Jing Yang, Qing-Mei He, Xin Wen, Ying Sun, Na Liu, Ying-Qin Li, Jun Ma
BACKGROUND: Increasing evidence support an important role for DNA methylation in nasopharyngeal carcinoma (NPC). Here, we explored the role of circadian clock gene Aryl Hydrocarbon Receptor Nuclear Translocator-Like (ARNTL) methylation in NPC. METHODS: We employed bisulfite pyrosequencing to determine the epigenetic change of ARNTL in NPC cell lines and tissues. ARNTL mRNA and protein expression in cell lines and tissues were detected by real-time PCR and western blotting...
January 8, 2019: Journal of Experimental & Clinical Cancer Research: CR
Qianru He, Lini Zhao, Xiaobai Liu, Jian Zheng, Yunhui Liu, Libo Liu, Jun Ma, Heng Cai, Zhen Li, Yixue Xue
BACKGROUND: RNA binding proteins (RBPs) have been reported to interact with RNAs to regulate gene expression. Circular RNAs (circRNAs) are a type of endogenous non-coding RNAs, which involved in the angiogenesis of tumor. The purpose of this study is to elucidate the potential roles and molecular mechanisms of MOV10 and circ-DICER1 in regulating the angiogenesis of glioma-exposed endothelial cells (GECs). METHODS: The expressions of circ-DICER1, miR-103a-3p and miR-382-5p were detected by real-time PCR...
January 8, 2019: Journal of Experimental & Clinical Cancer Research: CR
Huaying Dong, Jianguo Hu, Kejian Zou, Mulin Ye, Yuanwen Chen, Chengyi Wu, Xin Chen, Mingli Han
BACKGROUND: Trastuzumab resistance followed by metastasis is a major obstacle for improving the clinical outcome of patients with advanced human epidermal growth factor receptor 2-positive (HER-2+) breast cancer. While long non-coding RNAs (lncRNAs) can modulate cell behavior, the contribution of these RNAs in trastuzumab resistance and metastasis of HER-2+ breast cancer is not well known. In this study, we sought to identify the regulatory role of lncRNA in trastuzumab resistance and accompanied Epithelial-mesenchymal Transition (EMT) process in advanced HER-2+ breast cancer...
January 8, 2019: Molecular Cancer
Qin Xiang, Xiaoqian He, Junhao Mu, Haixi Mu, Dishu Zhou, Jun Tang, Qian Xiao, Yu Jiang, Guosheng Ren, Tingxiu Xiang, Weiyan Peng
In this study, we found that the phospholipase C delta1 (PLCD1) protein expression is reduced in colorectal tumor tissues compared with paired surgical margin tissues. PLCD1-promoted CpG methylation was detected in 29/64 (45%) primary colorectal tumors, but not in nontumor tissues. The PLCD1 RNA expression was also reduced in three out of six cell lines, due to PLCD1 methylation. The ectopic expression of PLCD1 resulted in inhibited proliferation and attenuated migration of colorectal tumor cells, yet promoted colorectal tumor cell apoptosis in vitro...
January 7, 2019: Journal of Cellular Physiology
Xiaolong Wang, Tong Chen, Yan Zhang, Ning Zhang, Chen Li, Yaming Li, Ying Liu, Hanwen Zhang, Wenjing Zhao, Bing Chen, Lijuan Wang, Qifeng Yang
Recently, long noncoding RNAs (lncRNAs) have become the key gene regulators and prognostic biomarkers in various cancers. Through microarray data, Linc00339 was identified as a candidate oncogenic lncRNA. We compared the expression levels of Linc00339 in several breast cancer cell lines and normal mammary gland epithelial cell line. The effects of Linc00339 on tumor progression were examined both in vitro and in vivo. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays were applied to evaluate the functions of Linc00339, miR-377-3p, and HOXC6 on cell proliferation...
January 7, 2019: Journal of Cellular Physiology
Jing Chen, Di Wu, Yue Zhang, Yong Yang, Yunfei Duan, Yong An
Long non-coding RNAs (lncRNAs) play important roles in a variety of tumours; however, their biological function and clinical significance in hepatocellular carcinoma (HCC) are still unclear. In this study, the clinical significance, biological function and regulatory mechanisms of lncRNA DCST1-AS1 in HCC were investigated. Differential lncRNAs in HCC were identified based on The Cancer Genome Atlas (TCGA) database. The biological function and mechanism of DCST1-AS1 were studied in vitro and in vivo. LncRNA DCST1-AS1 was highly expressed in HCC tissues, and the high expression of DCST1-AS1 was significantly correlated with larger tumours and shorter survival time...
January 7, 2019: Clinical Science (1979-)
Sarah T Diepstraten, Adam H Hart
Genetic lesions of the β-globin gene result in haemoglobinopathies such as β-thalassemia and sickle cell disease. To discover and test new molecular medicines for β-haemoglobinopathies, cell-based and animal models are now being widely utilised. However, multiple in vitro and in vivo models are required due to the complex structure and regulatory mechanisms of the human globin gene locus, subtle species-specific differences in blood cell development, and the influence of epigenetic factors. Advances in genome sequencing, gene editing, and precision medicine have enabled the first generation of molecular therapies aimed at reactivating, repairing, or replacing silenced or damaged globin genes...
January 2019: Blood Reviews
Da-Chuang Liu, Lin-Lin Song, Qing Liang, Lin Hao, Zhi-Guo Zhang, Cong-Hui Han
Prostate cancer (PCa) is one of the major cancers affecting males with high mortality around the world. Recent studies have found that some long noncoding RNAs play a critical part in the cellular processes of PCa. In our study, aberrant expressed lymphoid enhancer-binding factor-1 antisense RNA 1 (LEF1-AS1), microRNA-330-5p (miR-330-5p), and lymphoid enhancer-binding factor-1 (LEF1) were screened out from a microarray database, the role of the novel noncoding RNA regulatory circuitry in the initiation and development of PCa was investigated...
January 5, 2019: Journal of Cellular Physiology
Izzat F M Suffian, Julie T-W Wang, Farid N Faruqu, Julio Benitez, Yuya Nishimura, Chiaki Ogino, Akihiko Kondo, Khuloud T Al-Jamal
Hepatitis B virus core (HBc) particles acquire the capacity to disassemble and reassemble in a controlled manner, allowing entrapment and delivery of drugs and macromolecules to cells. HBc particles are made of 180-240 copies of 21 kDa protein monomers, assembled into 30-34 nm diameter icosahedral particles. In this study, we aimed at formulating HBc particles for the delivery of siRNA for gene silencing in vitro and in vivo . We have previously reported recombinant HBc particles expressing ZHER2 affibodies, specifically targeting human epidermal growth receptor 2 (HER2)-expressing cancer cells (ZHER2 -ΔHBc)...
July 27, 2018: ACS applied nano materials
Stephanie M Davis, Lisa A Collier, Elspeth A Foran, Christopher C Leonardo, Craig T Ajmo, Keith R Pennypacker
The aim of this study was to determine whether leukemia inhibitory factor (LIF) exerts its neuroprotective effects through signal transduction of the transcription factor myeloid zinc finger-1 (MZF-1). According to the hypothesis of this study, MZF-1 mediates LIF-induced neuroprotective signaling during ELVO through increased expression and transcriptional activity. To determine the in vivo role of MZF-1 in LIF-induced neuroprotection, we used Genomatix software was used to MZF-1 sites in the promoter region of the rat superoxide dismutase 3 (SOD3) gene...
January 5, 2019: Metabolic Brain Disease
Thomas K Smylla, Markus Meier, Anette Preiss, Dieter Maier
During development of higher animals, the Notch signalling pathway governs cell type specification by mediating appropriate gene expression responses. In the absence of signalling, Notch target genes are silenced by repressor complexes. In the model organism Drosophila melanogaster, the repressor complex includes the transcription factor Suppressor of Hairless [Su(H)] and Hairless (H) plus general co-repressors. Recent crystal structure analysis of the Drosophila Notch repressor revealed details of the Su(H)-H complex...
January 5, 2019: Development Genes and Evolution
Zhenqiang Wang, Liucan Wang, Neeraj Prabhakar, Yuxin Xing, Jessica M Rosenholm, Jixi Zhang, Kaiyong Cai
Combined photothermal and gene therapy provides a promising modality toward cancer treatment, yet facile integration and controlled codelivery of gene payloads and photothermal conversion agents (PTCAs) remains a great challenge. Inspired by the robust wet adhesion of marine mussels, we present a rationally designed nanosystem constructed by using hybrid mesoporous polydopamine nanoparticles (MPDA) with sub-100 nm sizes and a high photothermal conversion efficiency of 37%. The surface of the particles were modified with tertiary amines by the facile Michael addition/Schiff base reactions of PDA to realize high siRNA loading capacity (10 wt%)...
January 3, 2019: Acta Biomaterialia
Shangfeng Li, Shengkai Zhang, Jie Chen
Small nucleolar RNA host gene 16 (SNHG16) has been documented to be involved in the pathogenesis of human cancers. Here, we elucidated the biological roles and regulatory mechanism of SNHG16 in the pathogenesis of oral squamous cell carcinoma (OSCC). In this paper, we found that c-Myc and SNHG16 were overexpressed in OSCC tissues and cell lines compared with normal tissues and normal human oral keratinocytes cells. There was a notable positive correlation between SNHG16 and c-Myc expression in OSCC tissues...
January 4, 2019: Cancer Gene Therapy
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