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Molecular Therapy. Nucleic Acids

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https://www.readbyqxmd.com/read/30414568/angpt2-induces-mesangial-cell-apoptosis-through-the-microrna-33-5p-socs5-loop-in-diabetic-nephropathy
#1
Yi-Chun Tsai, Po-Lin Kuo, Wei-Wen Hung, Ling-Yu Wu, Ping-Hsun Wu, Wei-An Chang, Mei-Chuan Kuo, Ya-Ling Hsu
Diabetic nephropathy (DN) is the leading cause of end-stage renal disease. Mesangial cell (MC) loss is correlated with worsening renal function in DN. Disturbance of angiopoietin (Angpt)/Tie ligand-receptor system causes inflammation and abnormal angiogenesis. This association between elevated circulating Angpt2 and poor renal outcome has been in DN patients. However, the pathogenic role of Angpt2 in the MCs remains unknown. We found serum Angpt2 levels were elevated in type 2 diabetes mellitus (DM) patients and db/db mice, which correlated with albuminuria...
October 10, 2018: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/30396145/shorter-phosphorodiamidate-morpholino-splice-switching-oligonucleotides-may-increase-exon-skipping-efficacy-in-dmd
#2
Ugur Akpulat, Haicui Wang, Kerstin Becker, Adriana Contreras, Terence A Partridge, James S Novak, Sebahattin Cirak
Duchenne muscular dystrophy is a fatal muscle disease, caused by mutations in DMD, leading to loss of dystrophin expression. Phosphorodiamidate morpholino splice-switching oligonucleotides (PMO-SSOs) have been used to elicit the restoration of a partially functional truncated dystrophin by excluding disruptive exons from the DMD messenger. The 30-mer PMO eteplirsen (EXONDYS51) developed for exon 51 skipping is the first dystrophin-restoring, conditionally FDA-approved drug in history. Clinical trials had shown a dose-dependent variable and patchy dystrophin restoration...
October 10, 2018: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/30388624/long-non-coding-rna-pvt1-promotes-cell-proliferation-and-migration-by-silencing-angptl4-expression-in-cholangiocarcinoma
#3
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
https://www.readbyqxmd.com/read/30388622/cationic-oligospermine-oligonucleotide-conjugates-provide-carrier-free-splice-switching-in-monolayer-cells-and-spheroids
#4
Marc Nothisen, Phanélie Perche-Létuvée, Jean-Paul Behr, Jean-Serge Remy, Mitsuharu Kotera
We report the evaluation of 18-mer 2'-O-methyl-modified ribose oligonucleotides with a full-length phosphorothioate backbone chemically conjugated at the 5' end to the oligospermine units (Sn -: n = 5, 15, 20, 25, and 30 [number of spermine units]) as splice switching oligonucleotides (SSOs). These conjugates contain, in their structure, covalently linked oligocation moieties, making them capable of penetrating cells without transfection vector. In cell culture, we observed efficient cytoplasmic and nuclear delivery of fluorescein-labeled S20 -SSO by fluorescent microscopy...
October 10, 2018: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/30388621/lncrna-gas5-reverses-emt-and-tumor-stem-cell-mediated-gemcitabine-resistance-and-metastasis-by-targeting-mir-221-socs3-in-pancreatic-cancer
#5
Bingyan Liu, Shaoqiu Wu, Jun Ma, Shuo Yan, Zhengguang Xiao, Linhuang Wan, Feng Zhang, Mingyi Shang, Aiwu Mao
Dysregulated long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) mediating chemotherapeutic drug effects and metastasis in pancreatic cancer (PC) are key reasons for the poor prognosis of this disease. lncRNA growth arrest-specific 5 (GAS5) is reported to be a tumor suppressor in multiple cancers. However, the functions of GAS5 and its related miRNAs in PC are poorly understood. This study explored the potential functions and mechanisms of GAS5 in PC gemcitabine resistance and metastasis. The results show that overexpression of GAS5 suppressed the proliferation, migration, gemcitabine resistance, stem cell-like properties, and epithelial-mesenchymal transition (EMT) of PC cells by directly binding to and suppressing miR-221 expression and enhancing suppressor of cytokine signaling 3 (SOCS3) expression...
October 6, 2018: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/30414569/a-simplified-system-to-express-circularized-inhibitors-of-mirna-for-stable-and-potent-suppression-of-mirna-functions
#6
Yi Shu, Ke Wu, Zongyue Zeng, Shifeng Huang, Xiaojuan Ji, Chengfu Yuan, Linghuan Zhang, Wei Liu, Bo Huang, Yixiao Feng, Bo Zhang, Zhengyu Dai, Yi Shen, Wenping Luo, Xi Wang, Bo Liu, Yan Lei, Zhenyu Ye, Ling Zhao, Daigui Cao, Lijuan Yang, Xian Chen, Hue H Luu, Russell R Reid, Jennifer Moriatis Wolf, Michael J Lee, Tong-Chuan He
MicroRNAs (miRNAs) are an evolutionarily conserved class of small regulatory noncoding RNAs, binding to complementary target mRNAs and resulting in mRNA translational inhibition or degradation, and they play an important role in regulating many aspects of physiologic and pathologic processes in mammalian cells. Thus, efficient manipulations of miRNA functions may be exploited as promising therapeutics for human diseases. Two commonly used strategies to inhibit miRNA functions include direct transfection of chemically synthesized miRNA inhibitors and delivery of a gene vector that instructs intracellular transcription of miRNA inhibitors...
October 4, 2018: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/30388616/integrating-transcriptome-and-experiments-reveals-the-anti-diabetic-mechanism-of-cyclocarya-paliurus-formula
#7
Jing Li, Qiong Zhang, Weiwei Zeng, Yuxin Wu, Mei Luo, Yanhong Zhu, An-Yuan Guo, Xiangliang Yang
Type 2 diabetes (T2D) is generally regarded as a metabolic disorder disease with various phenotypic expressions. Traditional Chinese medicine (TCM) has been widely used for preventing and treating diabetes. In our study, we demonstrated that Cyclocarya paliurus formula extractum (CPE), a compound of TCM, can ameliorate diabetes in diabetic rats. Transcriptome profiles were performed to elucidate the anti-diabetic mechanisms of CPE on pancreas and liver. Pancreatic transcriptome analysis showed CPE treatment significantly inhibited gene expressions related to inflammation and apoptosis pathways, among which the transcription factors (TFs) nuclear factor κB (NF-κB), STAT, and miR-9a/148/200 may serve as core regulators contributing to ameliorate diabetes...
October 4, 2018: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/30388623/mir-125a-promotes-the-progression-of-giant-cell-tumors-of-bone-by-stimulating-il-17a-and-%C3%AE-catenin-expression
#8
Hua Jin, Dian-Wei Li, Shu-Nan Wang, Song Luo, Qing Li, Ping Huang, Jian-Min Wang, Meng Xu, Cheng-Xiong Xu
Giant cell tumors of bone (GCTBs) exhibit high recurrence and aggressive bone lytic behavior; but, the mechanism of GCTB progression is largely unknown. In GCTB, we detected abundant levels of miR-125a, which were associated with tumor extension, grade, and recurrence. miR-125a stimulates stromal cell tumorigenicity and growth in vivo by promoting the expression of interleukin-17A (IL-17A) and β-catenin. In contrast, inhibition of miR-125a suppressed stromal cell tumorigenicity and growth. Then, we found that miR-125a stimulates IL-17A by targeting TET2 and Foxp3, and it stimulates β-catenin expression by targeting APC and GSK3β in stromal cells...
October 2, 2018: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/30388617/targeting-long-noncoding-rna-in-glioma-a-pathway-perspective
#9
REVIEW
Junyang Li, Yihao Zhu, Handong Wang, Xiangjun Ji
Long noncoding RNAs (lncRNAs) participate extensively in biological processes of various cancers. The majority of these transcripts are uniquely expressed in differentiated tissues or specific cancer types. lncRNAs are aberrantly expressed in gliomas and exert diverse functions. In this article, we provided an overview of how lncRNAs regulate cellular processes in glioma, enumerated the lncRNAs that may act as glioma biomarkers, and showed their potential clinical implications.
October 2, 2018: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/30368217/circular-rnas-as-potential-theranostics-in-the-cardiovascular-system
#10
REVIEW
Yihua Bei, Tingting Yang, Lijun Wang, Paul Holvoet, Saumya Das, Joost P G Sluijter, Marta Chagas Monteiro, Yang Liu, Qiulian Zhou, Junjie Xiao
Cardiovascular diseases (CVDs) represent the largest contributor to mortality worldwide. Identification of novel therapeutic targets and biomarkers for CVDs is urgently needed. Circular RNAs (circRNAs) are endogenous, abundant, and stable non-coding RNAs formed by back-splicing events. Their role as regulators of gene expression has been increasingly reported. Notably, circRNAs mediate essential physiological and pathological processes in the cardiovascular system. Our first aim, therefore, is to summarize recent advances in the role of circRNAs in cardiac development as well as in pathogenesis of various CVDs...
October 2, 2018: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/30388625/genetic-strategies-for-hiv-treatment-and-prevention
#11
REVIEW
Alexander Falkenhagen, Sadhna Joshi
Conventional HIV gene therapy approaches are based on engineering HIV target cells that are non-permissive to viral replication. However, expansion of gene-modified HIV target cells has been limited in patients. Alternative genetic strategies focus on generating gene-modified producer cells that secrete antiviral proteins (AVPs). The secreted AVPs interfere with HIV entry, and, therefore, they extend the protection against infection to unmodified HIV target cells. Since any cell type can potentially secrete AVPs, hematopoietic and non-hematopoietic cell lineages can function as producer cells...
September 29, 2018: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/30388620/the-bipartite-network-projection-recommended-algorithm-for-predicting-long-non-coding-rna-protein-interactions
#12
Qi Zhao, Haifan Yu, Zhong Ming, Huan Hu, Guofei Ren, Hongsheng Liu
With the development of science and biotechnology, many evidences show that ncRNAs play an important role in the development of important biological processes, especially in chromatin modification, cell differentiation and proliferation, RNA progressing, human diseases, etc. Moreover, lncRNAs account for the majority of ncRNAs, and the functions of lncRNAs are expressed by the related RNA-binding proteins. It is well known that the experimental verification of lncRNA-protein relationships is a waste of time and expensive...
September 29, 2018: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/30388619/astrocyte-ev-induced-lincrna-cox2-regulates-microglial-phagocytosis-implications-for-morphine-mediated-neurodegeneration
#13
Guoku Hu, Ke Liao, Fang Niu, Lu Yang, Blake W Dallon, Shannon Callen, Changhai Tian, Jiang Shu, Juan Cui, Zhiqiang Sun, Yuri L Lyubchenko, Minhan Ka, Xian-Ming Chen, Shilpa Buch
Impairment of microglial functions, such as phagocytosis and/or dysregulation of immune responses, has been implicated as an underlying factor involved in the pathogenesis of various neurodegenerative disorders. Our previous studies have demonstrated that long intergenic noncoding RNA (lincRNA)-Cox2 expression is influenced by nuclear factor κB (NF-κB) signaling and serves as a coactivator of transcriptional factors to regulate the expression of a vast array of immune-related genes in microglia. Extracellular vesicles (EVs) have been recognized as primary facilitators of cell-to-cell communication and cellular regulation...
September 29, 2018: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/30388618/ns-065-ncnp-01-an-antisense-oligonucleotide-for-potential-treatment-of-exon-53-skipping-in-duchenne-muscular-dystrophy
#14
Naoki Watanabe, Tetsuya Nagata, Youhei Satou, Satoru Masuda, Takashi Saito, Hidetoshi Kitagawa, Hirofumi Komaki, Kazuchika Takagaki, Shin'ichi Takeda
Duchenne muscular dystrophy (DMD), the most common lethal heritable childhood disease, is caused by mutations in the DMD gene that result in the absence of functional dystrophin protein. Exon skipping mediated by antisense oligonucleotides has recently emerged as an effective approach for the restoration of dystrophin, and skipping of exon 51 of DMD has received accelerated approval. Identifying antisense sequences that can provide the highest possible skipping efficiency is crucial for future clinical applications...
September 27, 2018: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/30368216/expression-clinical-significance-and-functional-prediction-of-mnx1-in-breast-cancer
#15
Tian Tian, Meng Wang, Yuyao Zhu, Wenge Zhu, Tielin Yang, Hongtao Li, Shuai Lin, Cong Dai, Yujiao Deng, Dingli Song, Na Li, Zhen Zhai, Zhi-Jun Dai
Motor neuron and pancreas homeobox 1 (MNX1) is a key developmental gene. Previous studies found that it was upregulated in several tumors, but its role in breast cancer (BC) remains unclear. In order to have a better understanding of this gene in BC, we examined the expression of MNX1 in BC tissues and normal breast tissues by qRT-PCR and by analyzing data from The Cancer Genome Atlas (TCGA) database. We also assessed the association of MNX1 expression with BC clinicopathological features and investigated the impact of MNX1 on BC survival...
September 27, 2018: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/30347351/phosphorothioate-modified-ap613-1-specifically-targets-gpc3-when-used-for-hepatocellular-carcinoma-cell-imaging
#16
Lili Dong, Hongxin Zhou, Menglong Zhao, Xinghui Gao, Yang Liu, Dongli Liu, Wei Guo, Hongwei Hu, Qian Xie, Jia Fan, Jiang Lin, Weizhong Wu
Glypican-3 (GPC3), the cellular membrane proteoglycan, has been established as a tumor biomarker for early diagnosis of hepatocellular carcinoma (HCC). GPC3 is highly expressed in more than 70% HCC tissues detected by antibody-based histopathological systems. Recently, aptamers, a short single-strand DNA or RNA generated from systematic evolution of ligands by exponential enrichment (SELEX), were reported as potential alternatives in tumor-targeted imaging and diagnosis. In this study, a total of 19 GPC3-bound aptamers were successfully screened by capillary electrophoresis (CE)-SELEX technology...
September 27, 2018: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/30340138/aptamer-mir-34c-conjugate-affects-cell-proliferation-of-non-small-cell-lung-cancer-cells
#17
Valentina Russo, Alessia Paciocco, Alessandra Affinito, Giuseppina Roscigno, Danilo Fiore, Francesco Palma, Marco Galasso, Stefano Volinia, Alfonso Fiorelli, Carla Lucia Esposito, Silvia Nuzzo, Giorgio Inghirami, Vittorio de Franciscis, Gerolama Condorelli
MicroRNAs (miRNAs) are key regulators of different human processes that represent a new promising class of cancer therapeutics or therapeutic targets. Indeed, in several tumor types, including non-small-cell lung carcinoma (NSCLC), the deregulated expression of specific miRNAs has been implicated in cell malignancy. As expression levels of the oncosuppressor miR-34c-3p are decreased in NSCLC compared to normal lung, we show that reintroduction of miR-34c-3p reduces NSCLC cell survival in vitro. Further, in order to deliver the miR-34c-based therapeutic selectively to tumor cells, we took advantage of a reported nucleic acid aptamer (GL21...
September 27, 2018: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/30326428/inhibition-of-mir-449a-promotes-cartilage-regeneration-and-prevents-progression-of-osteoarthritis-in-in-vivo-rat-models
#18
Dawoon Baek, Kyoung-Mi Lee, Ki Won Park, Jae Wan Suh, Seong Mi Choi, Kwang Hwan Park, Jin Woo Lee, Sung-Hwan Kim
Traumatic and degenerative lesions of articular cartilage usually progress to osteoarthritis (OA), a leading cause of disability in humans. MicroRNAs (miRNAs) can regulate the differentiation of human bone marrow-derived mesenchymal stem cells (hBMSCs) and play important roles in the expression of genes related to OA. However, their functional roles in OA remain poorly understood. Here, we have examined miR-449a, which targets sirtuin 1 (SIRT1) and lymphoid enhancer-binding factor-1 (LEF-1), and observed its effects on damaged cartilage...
September 27, 2018: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/30326427/synthetic-circular-rna-functions-as-a-mir-21-sponge-to-suppress-gastric-carcinoma-cell-proliferation
#19
Xi Liu, John M Abraham, Yulan Cheng, Zhixiong Wang, Zhe Wang, Guanjun Zhang, Hassan Ashktorab, Duane T Smoot, Robert N Cole, Tatiana N Boronina, Lauren R DeVine, C Conover Talbot, Zhengwen Liu, Stephen J Meltzer
MicroRNA (miR) sponges containing miR binding sequences constitute a potentially powerful molecular therapeutic strategy. Recently, naturally occurring circular RNAs (circRNAs) were shown to function as efficient miR sponges in cancer cells. We hypothesized that synthetic circRNA sponges could achieve therapeutic loss-of-function targeted against specific miRs. Linear RNA molecules containing miR-21 binding sites were transcribed in vitro; after dephosphorylation and phosphorylation, circularization was achieved using 5'-3' end-ligation by T4 RNA ligase 1...
September 22, 2018: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/30321817/anti-cancer-drug-response-prediction-using-neighbor-based-collaborative-filtering-with-global-effect-removal
#20
Hui Liu, Yan Zhao, Lin Zhang, Xing Chen
Patients of the same cancer may differ in their responses to a specific medical therapy. Identification of predictive molecular features for drug sensitivity holds the key in the era of precision medicine. Human cell lines have harbored most of the same genetic changes found in patients' tumors and thus are widely used in the research of drug response. In this work, we formulated drug-response prediction as a recommender system problem and then adopted a neighbor-based collaborative filtering with global effect removal (NCFGER) method to estimate anti-cancer drug responses of cell lines by integrating cell-line similarity networks and drug similarity networks based on the fact that similar cell lines and similar drugs exhibit similar responses...
September 22, 2018: Molecular Therapy. Nucleic Acids
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