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In vivo gene silencing

Bradley J Goldstein, Rhea Choi, Garrett M Goss
Objectives: To investigate epigenetic mechanisms contributing to regulation of cellular renewal and neurogenesis in adult olfactory epithelium (OE). Study Design: Prospective basic science study. Methods: Olfactory basal cell cultures were prepared from adult mice per established protocols. in vivo studies were performed using the mouse methimazole lesion-regeneration paradigm. Nasal tissue sections were prepared from adult mice 7 days following lesion, or from unlesioned controls...
October 2018: Laryngoscope Investigative Otolaryngology
Hui-Ching Chuang, Ming-Huei Chou, Chih-Yen Chien, Jiin-Haur Chuang, Yu-Li Liu
Over the last decades, significant advances in targeted therapies have helped provide more effective treatment for head and neck cancer patients. However, chemo-resistance to cisplatin significantly contributes to treatment failure in the clinical management of patients. In response to chemotherapeutic agents, certain molecules inside the cell are released or secreted from damaged or dead/dying cells, named damage-associated molecular patterns (DAMPs), thereby initiating an immune response through interaction with pattern recognition receptors (PRRs), such as Toll-like receptors (TLRs)...
November 2018: Oral Oncology
Mushfiq H Shaikh, Adi Idris, Newell W Johnson, Sora Fallaha, Daniel T W Clarke, David Martin, Iain M Morgan, Brian Gabrielli, Nigel A J McMillan
OBJECTIVES: Human papilloma virus (HPV) is the main culprit in cancers of the cervix, penis, anus, skin, eye and head and neck. Current treatments for HPV cancers have not altered survival outcomes for 30 years and there is a significant lack of targeted therapeutic agents in the management of advanced HPV-related HNSCC. Here we show that survival and maintenance of HPV-positive HNC cells relies on the continuous expression of the major HPV oncogene, E7, and that Aurora kinases are critical for survival of high-risk HPV-positive HNC cells...
November 2018: Oral Oncology
Tianwen Lai, Mindan Wu, Chao Zhang, Luanqing Che, Feng Xu, Yong Wang, Yanping Wu, Nanxia Xuan, Chao Cao, Xufei Du, Bin Wu, Wen Li, Songmin Ying, Huahao Shen, Zhihua Chen
Histone deacetylase (HDAC) 2 is expressed in airway epithelium and plays a pivotal role in inflammatory cells. However, the role of HDAC2 in allergic airway inflammation remains poorly unknown. In the present study, we determined the role of HDAC2 in airway inflammation using in vivo models of HDM-induced allergic inflammation and in vitro cultures of human bronchial epithelial (HBE) cells exposed to HDM, IL17A, or both. We observed that HDM-challenged Hdac2+/- mice exhibited substantially enhanced infiltration of inflammatory cells...
November 8, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
Yan Lai, Alayne Cuzick, Xueqing Maggie Lu, Jianqiang Wang, Neerja Katiyar, Tokuji Tsuchiya, Karine Le Roch, John M McDowell, Eric Holub, Thomas Eulgem
The NLR-receptor RPP7 mediates race-specific immunity in Arabidopsis. Previous screens for enhanced downy mildew (edm) mutants identified the co-chaperone SGT1b (EDM1) and the PHD-finger protein EDM2 as critical regulators of RPP7. Here, we describe a third edm mutant compromised in RPP7 immunity, edm3. EDM3 encodes a nuclear-localized protein featuring an RNA-recognition motif. Like EDM2, EDM3 promotes histone H3 lysine 9 dimethylation (H3K9me2) at RPP7. Global profiling of H3K9me2 showed EDM3 to affect this silencing mark at a large set of loci...
November 8, 2018: Plant Journal: for Cell and Molecular Biology
Qian Hu, Lingli Li, Xin Zou, Lijun Xu, Ping Yi
Background: Recent epidemiologic studies have found that patients with diabetes have a higher risk of gastric cancer (GC), and the long-term use of metformin is associated with a lower risk of gastric cancer. It is believed that blocking tumor energy metabolic alterations is now emerging as a new therapeutic approach of cancer. Berberine, a natural isoquinoline alkaloid, could modulate lipid metabolism and glucose homeostasis by regulating the expression of HNF4α in many metabolic diseases. Here, we investigated the effect of Berberine on GC and its possible molecular mechanism through targeting HNF4α...
2018: Frontiers in Pharmacology
George B Kyei, Shanshan Meng, Rashmi Ramani, Austin Niu, Chandraiah Lagisetti, Thomas R Webb, Lee Ratner
The main obstacle to an HIV cure is the transcriptionally inert proviruses that persist in resting CD4 T cells and other reservoirs. None of the current approaches has significantly reduced the size of the viral reservoir. Hence, alternative approaches, such as permanent blocking of viral transcription, to achieve a sustained remission, need urgent attention. To identify cellular factors that may be important for this approach, we sought for host targets that when altered could block HIV transcription and reactivation...
November 6, 2018: MBio
Lijuan Zhou, Xianqi Zhang, Ralf Paus, Zhongfa Lu
Human skin organ culture (hSOC) is a simple but highly instructive and clinically relevant skin research method. It has been used for decades to study the development, differentiation, and function as well as the response to wounding or test agents of intact human skin in the presence of its appendages and all resident cell populations. hSOC has also proven useful in toxicological and oncological studies and studies of skin aging (both chronological aging and photoaging), skin energy metabolism, skin immunology, pigmentation biology, and cutaneous (neuro-)endocrinology and neurobiology...
October 16, 2018: Differentiation; Research in Biological Diversity
Ferenc Jankovics, Melinda Bence, Rita Sinka, Anikó Faragó, László Bodai, Aladár Pettkó-Szandtner, Karam Ibrahim, Zsanett Takács, Alexandra Brigitta Szarka-Kovács, Miklós Erdélyi
Self-renewal and differentiation of stem cells is one of the fundamental biological phenomena relying on proper chromatin organisation. In our study, we describe a novel chromatin regulator encoded by the Drosophila small ovary (sov) gene. We demonstrate that sov is required in both the germline stem cells (GSCs) and the surrounding somatic niche cells to ensure GSC survival and differentiation. Sov maintains niche integrity and function by repressing transposon mobility, not only in the germline, but also in the soma...
November 2, 2018: Development
Yang Yu, Mingjiong Zhang, Jie Liu, Boming Xu, Jian Yang, Ni Wang, Shuai Yan, Fei Wang, Xuezhi He, Guozhong Ji, Quanpeng Li, Lin Miao
Cholangiocarcinoma (CCA) is the most common biliary tract malignancy, with a low survival rate and limited treatment options. Long non-coding RNAs (lncRNAs) have recently been verified to have significant regulatory functions in many kinds of human cancers. It was discovered in this study that the lncRNA PVT1, whose expression is significantly elevated in CCA, could be a molecular marker of CCA. Experiments indicated that PVT1 knockdown greatly inhibited cell migration and proliferation in vitro and in vivo...
October 10, 2018: Molecular Therapy. Nucleic Acids
Hidenori Ito, Rika Morishita, Makoto Mizuno, Hidenori Tabata, Koh-Ichi Nagata
The hippocampus is generally considered as a brain center for learning and memory. We have recently established an electroporation-mediated gene transfer method to investigate the development of neonatal dentate granule cells in vivo. Using this new technique, we introduced knockdown vectors against Rac1 small GTPase into precursors for dentate granule cells at postnatal day 0. After 21 days, Rac1-deficient cells were frequently mispositioned between the granule cell layer (GCL) and hilus. About 60% of these mislocalized cells expressed a dentate granule cell marker, Prox1...
November 2, 2018: Hippocampus
Chen Yang, Siqi Wu, Xiaobo Wu, Xuejian Zhou, Shengming Jin, Haowen Jiang
Circular RNA UVRAG (circUVRAG), a kind of non-coding RNA, is derived and cyclized by part of the exon from the UVRAG gene. However, the role of circUVRAG in bladder cancer (BLCA) has not been reported. The purpose of this study was therefore to characterize the role of circUVRAG in BLCA. Bioinformatics analysis showed the interactive relationships among circUVRAG, miR-223, and fibroblast growth factor receptor2 (FGFR2). Quantitative real-time PCR was used to detect the expression of circUVRAG in BLCA cell lines...
November 2, 2018: Cancer Science
Luiza G Tunes, John M Allen, Ricardo M Zayas, Rubens L do Monte-Neto
Gold(I)-containing complexes are used in drug discovery research for rheumatoid arthritis, cancer, and parasitic infections. In this study, we tested the bioactivity of gold(I) complexes in vivo using planarians. The planarian Schmidtea mediterranea possesses orthologues of tumor suppressor genes, such as p53, that, when silenced, cause deregulation of cell proliferation and apoptosis. In this context, we tested two triethylphosphine-gold(I) complexes (AdO and AdT) to determine if they can attenuate phenotypes that result from p53 inhibition...
November 1, 2018: Scientific Reports
Mao-Hsuan Huang, Yi-Wen Chou, Ming-Hsun Li, Tina E Shih, Shinn-Zong Lin, Hong-Meng Chuang, Tzyy-Wen Chiou, Hong-Lin Su, Horng-Jyh Harn
Annually, 48,000 people die from pancreatic ductal adenocarcinoma (PDAC), ranking it the fourth among cancer-related deaths in the United States. Currently, anti-cancer drugs are not effective against PDAC, and only extends survival by 3 months. Aberrant DNA methylation has been shown to play an important role during carcinogenesis in PDAC, with approximately 80% of tumor overexpressing the DNA methyltransferase 1 (DNMT1) protein. In the present study, we used DNMTs as a screening platform to find a new DNMT inhibitor, n-butylidenephthalide (n-BP), which is identified from a Chinese herbal drug...
October 29, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Tongtong Yu, David T W Tzeng, Ran Li, Jianye Chen, Silin Zhong, Daqi Fu, Benzhong Zhu, Yunbo Luo, Hongliang Zhu
Background and Aims: In recent years, increasing numbers of long non-coding RNAs (lncRNAs) have been identified in humans, animals and plants, and several of them have been shown to play important roles in diverse biological processes. However, little work has been performed on the regulation mechanism of lncRNA biogenesis and expression, especially in plants. Compared with studies of tomato MADS-box transcription factor RIPENING INHIBITOR (RIN) target coding genes, there are few reports on its relationship to non-coding RNAs...
October 29, 2018: Annals of Botany
Rachel E Sexton, Ali H Hachem, Ali A Assi, Miriam A Bukhsh, David H Gorski, Cecilia L Speyer
Breast cancer remains a major cause of death among women. 15% of these cancers are triple negative breast cancer (TNBC), an aggressive subtype of breast cancer for which no current effective targeted therapy exists. We have previously demonstrated a role for mGluR1 in mediating tumor cell growth, endothelial cell proliferation, and tumor-induced angiogenesis in TNBC. In this study, we explore a role for mGluR1 in regulating inflammation in TNBC. GRM1 expression was silenced in MDA-MB-231 cells to study changes in expression of inflammatory genes regulated by mGluR1...
October 30, 2018: Scientific Reports
Shanshan Wang, Xuan Liu, Weijia Wang, Yi Tu, Chunliang Wang, Jinhong Mei, Jianping Xiong
Despite the molecular mechanisms of meningioma having been elucidated, the curative effects of current treatments for invasive and malignant meningiomas have been unsatisfactory. Our previous study found that HER2 protein was overexpressed in human meningiomas. However, only a few studies regarding the correlation between meningiomas and HER2 have been reported. The present study aimed to investigate the influence of silencing the Her2 gene on the proliferation and angiogenesis of human malignant meningioma cells...
September 2018: Annals of Clinical and Laboratory Science
Yifan Lian, Jiebin Yang, Yikai Lian, Chuangxing Xiao, Xuezhen Hu, Hongzhi Xu
BACKGROUND: Recent studies highlight pseudogene derived long non-coding RNAs (lncRNAs) as key regulators of cancer biology. However, few of them have been well characterized in pancreatic cancer. Here, we aimed to identify the association between pseudogene derived lncRNA DUXAP8 and growth of pancreatic cancer cells. METHODS: We screened for pseudogene derived lncRNAs associated with human pancreatic cancer by comparative analysis of three independent datasets from GEO...
October 26, 2018: Cancer communications
Xiangpan Li, Huibo Zhang, Xiaofei Wu
Long noncoding RNAs (lncRNAs) participate in numerous of human cancer tumorigenesis. Nevertheless, the in-depth molecular mechanism that lncRNAs regulate the gliomagenesis is still ambiguous. In this research, our study invests energy in the biologic roles of lncRNA DLX6-AS1 on the glioma tumorigenesis. Here, we demonstrated that DLX6-AS1 expression was both high-expressed in the glioma cells and tissue, and the overexpression of DLX6-AS1 was clinically correlated with the poor outcome of glioma patients. In the cellular functional assays, silenced DLX6-AS1 expression by siRNAs inhibited the proliferation, invasion and tumor growth in vitro and in vivo, while the enhanced DLX6-AS1 expression by plasmids promotes them...
October 23, 2018: Gene
Zhi-Jun Jiang, Qing-Hua Shen, Hai-Yong Chen, Zhe Yang, Ming-Qi Shuai, Shu-Sen Zheng
Liver fibrosis is a serious threat to human health, and there is currently no effective clinical drug for treatment of the disease. Although Galectin‑1 is effective, its role in liver function, inflammation, matrix metalloproteinases and the activation of hepatic stellate cells (HSCs) remains to be elucidated. The aim of the present study was to elucidate the effect of Galectin‑1 on the activation, proliferation and apoptosis of HSCs in a mouse model of liver fibrosis. Following successful model establishment and tissue collection, mouse HSCs (mHSCs) were identified and an mHSC line was constructed...
October 23, 2018: International Journal of Molecular Medicine
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