Abstract:
:Abnormal synthesis of extracellular matrix (ECM), especially collagen type IV (Col IV), in human retinal capillary endothelial cells (HRCECs) and resultant basement membrane (BM) thickening is the most prominent and characteristic feature of early diabetic retinopathy (DR). Osteopontin (OPN) has been shown to play an important role in the pathogenesis of DR and specifically, found to be critically involved in diabetic nephropathy, as it can upregulate many factors, like collagen IV. However, the precise role of OPN in the pathogenesis of DR and the underlying mechanisms remain unclear. In this study, 51 differentially expressed microRNAs (miRNAs; 42 miRNAs upregulated and 9 miRNAs downregulated) were first identified in retina of streptozotocin (STZ)-induced diabetic mice with DR. Among these miRNAs, we identified miRNA (miR)-29a as a prominent miRNA that targeted and directly downregulated Col IV expression through database prediction and dual-luciferase reporter assay, which was further confirmed in HRCECs using miR-29a mimic, miR-29a inhibitor, and pre-miR-29a transfection. Furthermore, OPN upregulated Col IV expression via a miR-29a-repressed pathway in HRCECs. Taken together, these results provided a miR-29a-repressing mechanism through which OPN plays roles in abnormal synthesis of Col IV in HRCECs and resultant BM thickening, contributing to the pathogenesis of DR.
journal_name
Mol Ther Nucleic Acidsjournal_title
Molecular therapy. Nucleic acidsauthors
Duan P,Chen S,Zeng Y,Xu H,Liu Ydoi
10.1016/j.omtn.2020.02.001subject
Has Abstractpub_date
2020-06-05 00:00:00pages
242-251issn
2162-2531pii
S2162-2531(20)30073-1journal_volume
20pub_type
杂志文章abstract::Cutaneous squamous cell carcinoma (CSCC) is a malignant proliferation of cutaneous epithelium that has been observed to have an alarming rise in incidence. Numerous studies have demonstrated microRNAs (miRNAs or miRs) as important biomarkers in the diagnosis, prognosis, and treatment of CSCC. This study aims to invest...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章
doi:10.1016/j.omtn.2020.04.014
更新日期:2020-09-04 00:00:00
abstract::Neovascular age-related macular degeneration (AMD) is characterized by the formation of choroidal neovascularization, which is responsible for more than 80% of cases of severe vision loss. Ubiquitin protein ligase E3D (UBE3D) gene missense has been proven to be associated with neovascular AMD in the East Asian populat...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章
doi:10.1016/j.omtn.2020.02.010
更新日期:2020-06-05 00:00:00
abstract::miR-221 is overexpressed in several malignancies where it promotes tumor growth and survival by interfering with gene transcripts, including p27Kip1, PUMA, PTEN, and p57Kip2. We previously demonstrated that a novel 13-mer miR-221 inhibitor (locked nucleic acid [LNA]-i-miR-221) exerts antitumor activity against human c...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章
doi:10.1016/j.omtn.2020.01.036
更新日期:2020-06-05 00:00:00
abstract::Lipid nanoparticles (LNPs) have been used to successfully deliver small interfering RNAs (siRNAs) to target cells in both preclinical and clinical studies and currently are the leading systems for in vivo delivery. Here, we propose the use of an ordinary differential equation (ODE)-based model as a tool for optimizing...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章
doi:10.1016/j.omtn.2017.04.003
更新日期:2017-06-16 00:00:00
abstract::Malignant glioma is a severe cancer with a poor prognosis. Local occurrence and rare metastases of malignant glioma make it a suitable target for gene therapy. Several studies have demonstrated the importance of Src kinase in different cancers. However, these studies have focused mainly on Src-deficient mice or pharma...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章
doi:10.1038/mtna.2012.13
更新日期:2012-05-01 00:00:00
abstract::Continuous innovation of revolutionizing genome engineering technologies calls for an intensified focus on new delivery technologies that not only match the inventiveness of genome editors but also enable the combination of potent delivery and time-restricted action of genome-modifying bits and tools. We have previous...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章
doi:10.1016/j.omtn.2018.02.006
更新日期:2018-06-01 00:00:00
abstract::Targeted nucleases are influential instruments for intervening in genome revision with great accuracy. RNA-guided Cas9 nucleases produced from clustered regularly interspaced short palindromic repeats (CRISPR)-Cas systems have noticeably altered the means to modify the genomes of distinct organisms. They can be notabl...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章,评审
doi:10.1038/mtna.2016.95
更新日期:2016-11-15 00:00:00
abstract::A hexanucleotide GGGGCC expansion in intron 1 of chromosome 9 open reading frame 72 (C9orf72) gene is the most frequent cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). The corresponding repeat-containing sense and antisense transcripts cause a gain of toxicity through the accumulation o...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章
doi:10.1016/j.omtn.2019.02.001
更新日期:2019-06-07 00:00:00
abstract::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 ...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章
doi:10.1016/j.omtn.2018.09.020
更新日期:2018-12-07 00:00:00
abstract::Hepatocellular carcinoma (HCC) has high fatality rate and limited therapeutic options. Here, we propose a new anti-HCC approach with high cancer-selectivity and efficient anticancer effects, based on adenovirus-mediated Tetrahymena group I trans-splicing ribozymes specifically inducing targeted suicide gene activity t...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章
doi:10.1016/j.omtn.2020.10.036
更新日期:2020-10-31 00:00:00
abstract::Due to highly enzymatic d-stereoselectivity, l-nucleotides (l-2'-deoxynucleoside 5'-triphosphates [l-dNTPs]) are not natural targets of polymerases. In this study, we synthesized series of l-thymidine (l-T)-modified DNA strands and evaluated the processivity of nucleotide incorporation for transcription by T7 RNA poly...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章
doi:10.1016/j.omtn.2020.06.023
更新日期:2020-09-04 00:00:00
abstract::As a diverse and abundant class of endogenous RNAs, circular RNAs (circRNAs) participate in processes including cell proliferation and apoptosis. Nevertheless, few researchers have investigated the function of circRNAs in bovine muscle development. Based on existing sequencing data, we identified circINSR. The localiz...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章
doi:10.1016/j.omtn.2019.12.032
更新日期:2020-03-06 00:00:00
abstract::Thanks to their ability to recognize biomolecular targets with high affinity and specificity, nucleic acid aptamers are increasingly investigated as diagnostic and therapeutic tools, particularly when their targets are cell-surface receptors. Here, we investigate the relationship between the folding of an anti-mouse t...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章
doi:10.1038/mtna.2013.71
更新日期:2014-01-28 00:00:00
abstract::We previously demonstrated that expression of Notch-1 is associated with poor prognosis in lung adenocarcinoma (LAD) patients. The aim of this study is to reveal whether Notch-1 was associated with Taxanes-resistant LAD and, the underlying mechanisms. We collected 39 patients of advanced LAD treated with Taxanes and f...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章
doi:10.1038/mtna.2016.82
更新日期:2016-10-11 00:00:00
abstract::Emerging evidence has demonstrated that miR-223 is critically involved in the progression of pancreatic cancer (PC); however, the underlying mechanisms are not fully elucidated. In the present study, we explored the molecular basis of miR-223-mediated tumor progression in PC. We performed numerous approaches including...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章
doi:10.1016/j.omtn.2019.01.009
更新日期:2019-03-01 00:00:00
abstract::A gene therapeutic platform needs to be both efficient and safe. The criterion of safety is particularly important for diseases like hepatocellular carcinoma (HCC), which develop in a background of an already compromised liver. Gene vectors can be constructed either by targeting HCC or by detargeting liver and/or othe...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章
doi:10.1016/j.omtn.2018.08.016
更新日期:2018-12-07 00:00:00
abstract::Spermatogonial stem cells (SSCs) have significant applications in reproductive and regenerative medicine. However, nothing is known about genes in mediating human SSCs. Here we have explored for the first time the function and mechanism of P21-activated kinase 1 (PAK1) in regulating the proliferation and apoptosis of ...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章
doi:10.1016/j.omtn.2018.06.006
更新日期:2018-09-07 00:00:00
abstract::MicroRNAs (miRNAs or miRs) play crucial roles in biological and pathological processes. Some miRNAs also appear as promising biomarkers and therapeutic tools. However, the epitranscriptomic regulation of miRNAs is not yet fully elucidated in all of their fields of application. We report that adenosine methylation of m...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章
doi:10.1016/j.omtn.2020.08.010
更新日期:2020-08-14 00:00:00
abstract::Circular RNAs (circRNAs) represent a class of noncoding RNAs with a wide expression pattern, and they constitute an important layer of the genome regulatory network. To date, the expression pattern and regulatory potency of circRNAs in the retina, a key part of the central nervous system, are not yet well understood. ...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章
doi:10.1016/j.omtn.2019.11.016
更新日期:2020-03-06 00:00:00
abstract::The genetic diversity of the influenza virus hinders the use of broad spectrum antiviral drugs and favors the appearance of resistant strains. Single-stranded DNA aptamers represent an innovative approach with potential application as antiviral compounds. The mRNAs of influenza virus possess a 5'cap structure and a 3'...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章
doi:10.1038/mtna.2016.20
更新日期:2016-04-12 00:00:00
abstract::As key regulators of gene expression, microRNAs (miRNAs) have emerged as targets in basic experimentation and therapy. Administration of DNA-encoded RNA molecules, targeting miRNAs through base pairing, is one viable strategy for inhibiting specific miRNAs. A naturally occurring circular RNA (circRNA), ciRS-7, serving...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章
doi:10.1016/j.omtn.2018.09.009
更新日期:2018-12-07 00:00:00
abstract::Gene knockdown using short hairpin RNAs (shRNAs) is a promising strategy for targeting dominant mutations; however, delivering too much shRNA can disrupt the processing of endogenous microRNAs (miRNAs) and lead to toxicity. Here, we sought to understand the effect that excessive shRNAs have on muscle miRNAs by treatin...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章
doi:10.1016/j.omtn.2019.12.007
更新日期:2020-03-06 00:00:00
abstract::Long non-coding RNA (lncRNA) H19 is associated with inflammatory diseases, but the molecular mechanism of H19 in the inflammatory process of ankylosing spondylitis (AS) is unclear. Here, we investigated the role of H19 and its downstream molecules in the inflammation of AS by microarray analysis, qRT-PCR, western blot...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章
doi:10.1016/j.omtn.2019.11.025
更新日期:2020-03-06 00:00:00
abstract::Gemcitabine has been considered a first-line chemotherapy agent for the treatment of pancreatic cancer. However, the initial response rate of gemcitabine is low and chemoresistance occurs frequently. Aptamers can be effectively internalized into cancer cells via binding to target molecules with high affinity and speci...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章
doi:10.1016/j.omtn.2018.06.003
更新日期:2018-09-07 00:00:00
abstract::Exosomes are membrane-enclosed nanovesicles that shuttle active cargoes, such as mRNAs and microRNAs (miRNAs), between different cells. Mesenchymal stem cells (MSCs) are able to migrate to the tumor sites and exert complex functions over tumor progress. We investigated the effect of human bone marrow-derived MSC (BMSC...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章
doi:10.1016/j.omtn.2019.08.010
更新日期:2019-12-06 00:00:00
abstract::Highly active antiretroviral therapy (HAART) has significantly improved the quality of life and the life expectancy of HIV-infected individuals. Still, drug-induced side effects and emergence of drug-resistant viral variants remain important issues that justify the exploration of alternative therapeutic options. One s...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章
doi:10.1038/mtna.2013.48
更新日期:2013-09-03 00:00:00
abstract::Circular RNAs (circRNAs) were recently reported to be involved in the pathogenesis of ovarian cancer (OC); however, the molecular mechanisms of circRNAs in tumor progression and paclitaxel (PTX) resistance of OC remain largely undetermined. Here, we focused on circTNPO3 (hsa_circ_0001741), which is located on chromoso...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章
doi:10.1016/j.omtn.2020.06.002
更新日期:2020-09-04 00:00:00
abstract::As the human lifespan has increased due to developments in medical technology, the number of patients with neurological diseases has rapidly increased. Therefore, studies on effective treatments for neurological diseases are becoming increasingly important. To perform these studies, it is essential to obtain a large n...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章
doi:10.1016/j.omtn.2018.12.009
更新日期:2019-03-01 00:00:00
abstract::Transcription factor Yin Yang 1 (YY1) is upregulated in multiple tumors and plays essential roles in tumor proliferation and metastasis. However, the function of YY1 in breast cancer stemness remains unclear. Herein, we found that YY1 expression was negatively correlated with the overall survival and relapse-free surv...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章
doi:10.1016/j.omtn.2020.06.018
更新日期:2020-09-04 00:00:00
abstract::Nonviral gene delivery is a promising therapeutic approach because of its safety and controllability, yet limited gene transfer efficacy is a common issue. Most nonviral strategies rely upon endosomal escape designs; however, endosomal escape is often uncorrelated with improved gene transfer and membranolytic structur...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章
doi:10.1038/mtna.2015.2
更新日期:2015-02-10 00:00:00