Abstract:
:Indoleamine 2,3-dioxygenase (IDO) is a rate limiting enzyme in tryptophan-degrading pathways and IDO activity results in immune suppression. Targeting IDO is a strategy of cancer immunotherapies. Our previous studies demonstrate that delivery of short hairpin against IDO (IDO shRNA) suppresses tumor growth and increases neutrophils infiltration into tumor. Neutrophils reveal antitumorigenic "N1" or protumorigenic "N2" phenotype in tumor microenvironment. However, the function of IDO shRNA-induced neutrophils is not clear. The LLC1 lung cancer model was used to investigate the role of these neutrophils. Intramuscular injection of IDO shRNA or IDO inhibitor treatment delayed tumor growth and both treatments increased neutrophil infiltration in tumor. Enriched tumor-infiltrating neutrophils expressed both high level of tumor necrosis factor-α and tumor necrosis factor-β (N1 and N2 associated molecules, respectively). In addition, IDO shRNA treatment induced interferon-γ and tryptophan transfer RNA expression in splenocytes. Systematic depletion of neutrophils abolished the IDO shRNA-induced therapeutic effect but did not affect the effect of IDO inhibitor. The levels of interferon-γ and tumor necrosis factor-α were suppressed in IDO shRNA treatment splenocytes after neutrophils depletion. In conclusion, these tumor-infiltrating neutrophils show antitumorigenic phenotype in spleen after IDO shRNA treatment in a murine lung cancer model.
journal_name
Mol Ther Nucleic Acidsjournal_title
Molecular therapy. Nucleic acidsauthors
Liu KT,Liu YH,Liu HL,Chong IW,Yen MC,Kuo PLdoi
10.1038/mtna.2016.105subject
Has Abstractpub_date
2016-12-06 00:00:00pages
e397issue
12issn
2162-2531pii
S2162-2531(17)30021-5journal_volume
5pub_type
杂志文章abstract::Methyltransferase-like 3 (METTL3) is the main enzyme for N6-methyladenosine (m6A)-based methylation of RNAs and it has been implicated in many biological and pathophysiological processes. In this study, we aimed to explore the potential involvement of METTL3 in osteoblast differentiation and decipher the underlying ce...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章
doi:10.1016/j.omtn.2019.12.001
更新日期:2020-03-06 00:00:00
abstract::Transactivation of inflammatory and immune mediators in asthma is tightly regulated by nuclear factor κB (NF-κB) and signal transducer and activator of transcription 6 (STAT6). Therefore, we investigated the efficacy of simultaneous inhibition of NF-κB and STAT6 using a chimeric decoy strategy to prevent asthma exacer...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章
doi:10.1016/j.omtn.2017.12.005
更新日期:2018-03-02 00:00:00
abstract::Engineered nuclease-mediated gene targeting through homologous recombination (HR) in hematopoietic stem and progenitor cells (HSPCs) has the potential to treat a variety of genetic hematologic and immunologic disorders. Here, we identify critical parameters to reproducibly achieve high frequencies of RNA-guided (singl...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章
doi:10.1016/j.omtn.2018.04.017
更新日期:2018-09-07 00:00:00
abstract::Adeno-associated virus (AAV) is the most common vector for clinical gene therapy of the CNS. This popularity originates from a high safety record and the longevity of transgene expression in neurons. Nevertheless, clinical efficacy for CNS indications is lacking, and one reason for this is the relatively limited sprea...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章
doi:10.1016/j.omtn.2017.06.011
更新日期:2017-09-15 00:00:00
abstract::Cardiac hypertrophy accompanied by maladaptive cardiac remodeling is the uppermost risk factor for the development of heart failure. Long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) have various biological functions, and their vital role in the regulation of cardiac hypertrophy still needs to be explored. In this...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章
doi:10.1016/j.omtn.2017.12.018
更新日期:2018-03-02 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::Antisense oligonucleotides complementary to RNA targets promise generality and ease of drug design. The first systemically administered antisense drug was recently approved for treatment and others are in clinical development. Chemical modifications that increase the hybridization affinity of oligonucleotides are reas...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章
doi:10.1038/mtna.2013.72
更新日期:2014-02-18 00:00:00
abstract::We developed an efficient system for delivering short interfering RNA (siRNA) to the liver by using α-tocopherol conjugation. The α-tocopherol-conjugated siRNA was effective and safe for RNA interference-mediated gene silencing in vivo. In contrast, when the 13-mer LNA (locked nucleic acid)-DNA gapmer antisense oligon...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章
doi:10.1038/mtna.2014.72
更新日期:2015-01-13 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::The role of long non-coding RNA (lncRNA) in the regulation of bovine skeletal muscle development remains poorly understood. The present study investigated the function and regulatory mechanism of a novel lncRNA, insulin-like growth factor 2 antisense transcript (IGF2 AS), in bovine myoblast proliferation and different...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章
doi:10.1016/j.omtn.2020.07.002
更新日期:2020-09-04 00:00:00
abstract::MicroRNAs (miRNAs) are small noncoding RNAs approximately 20-25 nt in length, which play crucial roles through directly binding to corresponding 3' UTR of targeted mRNAs. It has been reported that miRNAs are involved in numerous of diseases, including cancers. Recently, miR-134 has been identified to dysregulate in ha...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章,评审
doi:10.1016/j.omtn.2016.11.003
更新日期:2017-03-17 00:00:00
abstract::Base editing systems show their power in modeling and correcting the pathogenic mutations of genetic diseases. Previous studies have already demonstrated the editing efficiency of BE3-mediated C-to-T conversion in human embryos. However, the precision and efficiency of a recently developed adenine base editor (ABE), w...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章
doi:10.1016/j.omtn.2019.05.021
更新日期:2019-09-06 00:00:00
abstract::Leukemias arise from genetic alterations in normal hematopoietic stem or progenitor cells, leading to impaired regulation of proliferation, differentiation, apoptosis, and survival of the transformed cells. With the advent of RNA interference (RNAi) and the short interfering RNA (siRNA) as its pharmacological mediator...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章,评审
doi:10.1038/mtna.2015.13
更新日期:2015-05-12 00:00:00
abstract::Treatment of pancreatic ductal adenocarcinoma (PDAC) remains a clinical challenge. There is an urgent need to develop novel strategies to enhance survival and improve patient prognosis. MicroRNAs (miRNAs) play critical roles as oncogenes or tumor suppressors in the regulation of cancer development and progression. In ...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章
doi:10.1016/j.omtn.2019.11.010
更新日期:2020-03-06 00:00:00
abstract::Cardiomyocyte differentiation derived from embryonic stem cells (ESCs) is a complex process involving molecular regulation of multiple levels. In this study, we first identify and compare differentially expressed gene (DEG) signatures of ESC-derived cardiomyocyte differentiation (ESCDCD) in humans and mice. Then, the ...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章
doi:10.1016/j.omtn.2020.07.011
更新日期:2020-09-04 00:00:00
abstract::Current acute myeloid leukemia (AML) disease models face severe limitations because most of them induce un-physiological gene expressions that do not represent conditions in AML patients and/or depend on external promoters for regulation of gene expression/repression. Furthermore, many AML models are based on reciproc...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章
doi:10.1016/j.omtn.2016.12.012
更新日期:2017-03-17 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::[This corrects the article DOI: 10.1038/mtna.2016.46.]. ...
journal_title:Molecular therapy. Nucleic acids
pub_type: 已发布勘误
doi:10.1016/j.omtn.2020.08.028
更新日期:2020-11-19 00:00:00
abstract::In this study, chemical modification of 2'-deoxyinosine (2'-dI) and D-/L-isothymidine (D-/L-isoT) was performed on AS1411. They could promote the nucleotide-protein interaction by changing the local conformation. Twenty modified sequences were obtained, FCL-I and FCL-II showed the most noticeable activity improvement....
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章
doi:10.1016/j.omtn.2017.09.010
更新日期:2017-12-15 00:00:00
abstract::Alzheimer's disease (AD) is a multifactorial, fatal neurodegenerative disorder characterized by the abnormal accumulation of Aβ and Tau deposits in the brain. There is no cure for AD, and failure at different clinical trials emphasizes the need for new treatments. In recent years, significant progress has been made to...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章
doi:10.1038/mtna.2015.33
更新日期:2015-10-06 00:00:00
abstract::We previously found that inhibition of p66Shc confers protection against hepatic stellate cell (HSC) activation during liver fibrosis. However, the effect of p66Shc on HSC proliferation, as well as the mechanism by which p66Shc is modulated, remains unknown. Here, we elucidated the effect of p66Shc on HSC proliferatio...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章
doi:10.1016/j.omtn.2020.07.013
更新日期:2020-09-04 00:00:00
abstract::Targeted transcriptional modulation in the central nervous system (CNS) can be achieved by adeno-associated virus (AAV) delivery of CRISPR activation (CRISPRa) and interference (CRISPRi) transgenes. To enable AAV packaging, we constructed minimal CRISPRa and CRISPRi transgenes by fusing catalytically inactive Staphylo...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章
doi:10.1016/j.omtn.2019.04.015
更新日期:2019-06-07 00:00:00
abstract::MicroRNAs (miRNAs) are an important class of small noncoding RNA molecules that serve as excellent biomarkers of various diseases. However, current miRNA biomarkers, including those comprised of multiple miRNAs, work at a single-miRNA level but not at a miRNA-set level, which is defined as a group of miRNAs sharing co...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章
doi:10.1016/j.omtn.2020.07.004
更新日期:2020-09-04 00:00:00
abstract::DNA vaccine can be modified to increase protein production and modulate immune response. To enhance the efficiency of a P815 mastocytoma DNA vaccine, the P1A gene sequence was optimized by substituting specific codons with synonymous ones while modulating the number of CpG motifs. The P815A murine antigen production w...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章
doi:10.1016/j.omtn.2017.07.011
更新日期:2017-09-15 00:00:00
abstract::Gene therapy holds considerable promise for the functional cure of HIV-1 infection and, in this context, RNA interference (RNAi)-based approaches represent powerful strategies. Stable expression of small interfering RNAs (siRNAs) targeting HIV genes or cellular cofactors has the potential to render HIV-1 susceptible c...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章
doi:10.1038/mtna.2016.24
更新日期:2016-04-19 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::The knockdown of myostatin, a negative regulator of skeletal muscle mass may have important implications in disease conditions accompanied by muscle mass loss like cancer, HIV/AIDS, sarcopenia, muscle atrophy, and Duchenne muscular dystrophy (DMD). In DMD patients, where major muscle loss has occurred due to a lack of...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章
doi:10.1038/mtna.2012.54
更新日期:2012-12-18 00:00:00
abstract::Circular RNA (circRNA), as a kind of novel identified non-coding RNA, has become the focus of attention for its vital physiological and pathological roles. However, the function and mechanism of circRNAs in the regulation of cancer progression are largely unknown. In the present study we found a circRNA termed circHMC...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章
doi:10.1016/j.omtn.2020.03.014
更新日期:2020-06-05 00:00:00
abstract::VPS33B is reported to be a tumor suppressor in hepatocellular carcinoma, nasopharyngeal carcinoma, colon cancer, and lung adenocarcinoma. Here, we observed that reduced VPS33B protein level was an unfavorable factor that promoted the pathogenesis of non-small cell lung cancer (NSCLC) in clinical specimens. We achieved...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章
doi:10.1016/j.omtn.2020.11.010
更新日期:2020-11-17 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