Abstract:
:Although patients with non-small cell lung cancer harboring activating mutations in the epidermal growth factor receptor (EGFR) show good clinical response to EGFR tyrosine kinase inhibitors (TKIs), patients eventually develop acquired resistance. Previous studies have shown that several microRNAs (miRNAs) are involved in EGFR TKI resistance. Here, we aimed to investigate whether miR-146b-5p sensitizes the EGFR TKI-resistant lung cancer cells. Clinical analysis showed that miR-146b-5p expression in lung cancer cells isolated from pleural effusions of treatment-naive patients was significantly higher than that after acquiring resistance to EGFR TKI treatment. Ectopic expression of miR-146b-5p in EGFR TKI-resistant cells enhanced EGFR TKI-induced apoptosis. The same results were observed in EGFR-dependent and -independent osimertinib-resistant primary cancer cells (PE3479 and PE2988). Mechanically, miR-146b-5p suppressed nuclear factor κB (NF-κB) activity and NF-κB-related IL-6 and IL-8 production by targeting IRAK1. A negative correlation was observed between miR-146b-5p and IRAK1 in clinical specimens. In rescue experiments, restoration of IRAK1 expression reversed the effects of miR-146b-5p on EGFR TKI sensitivity and recovered NF-κB-regulated IL-6 and IL-8 production. In conclusion, miR-146b-5p/IRAK1/NF-κB signaling is important in promoting EGFR TKI resistance, and miR-146b-5p may be a useful tool for overcoming EGFR TKI resistance.
journal_name
Mol Ther Nucleic Acidsjournal_title
Molecular therapy. Nucleic acidsauthors
Liu YN,Tsai MF,Wu SG,Chang TH,Tsai TH,Gow CH,Wang HY,Shih JYdoi
10.1016/j.omtn.2020.09.015subject
Has Abstractpub_date
2020-09-16 00:00:00pages
471-483issn
2162-2531pii
S2162-2531(20)30286-9journal_volume
22pub_type
杂志文章abstract::Exosomes mediate cell-cell crosstalk in cancer progression by transferring a variety of biomolecules, including long noncoding RNAs (lncRNAs). Long non-coding RNA urothelial carcinoma-associated (UCA1) is a well-known lncRNA associated with the development and progression of various cancers, including colorectal cance...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章
doi:10.1016/j.omtn.2019.12.009
更新日期:2020-03-06 00:00:00
abstract::Recent studies have shown the effect of microRNAs on HSC activation and transformation, which is essential for the pathogenesis of liver fibrosis. In our study, we explored the role of miR-185 in liver fibrosis. Plasma miR-185 was detected in hepatitis B virus-related liver fibrosis patients (S2/3, n = 10) by Illumina...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章
doi:10.1016/j.omtn.2017.11.010
更新日期:2018-03-02 00:00:00
abstract::As the world population grows, muscle atrophy leading to muscle wasting could become a bigger risk. Long noncoding RNAs (lncRNAs) are known to play important roles in muscle growth and muscle atrophy. Meanwhile, it has recently come to light that many putative small open reading frames (sORFs) are hidden in lncRNAs; h...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章
doi:10.1016/j.omtn.2020.12.003
更新日期:2020-12-10 00:00:00
abstract::Mitochondrial DNA (mtDNA) haplogroups are associated with various types of cancer; however, the molecular mechanisms by which mtDNA haplogroups affect primary hepatocellular carcinoma (HCC) are not known. In this study, we carried out a case-control study on 388 HCC patients and 511 geographically matched asymptomatic...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章
doi:10.1016/j.omtn.2019.09.001
更新日期:2019-12-06 00:00:00
abstract::5-methylcytosine (m5C) is one of the most common and abundant post-transcriptional modifications (PTCMs) in RNA. Recent studies showed that m5C plays important roles in many biological functions such as RNA metabolism and cell fate decision. Because most experimental methods that determine m5C sites across the transcr...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章
doi:10.1016/j.omtn.2019.10.008
更新日期:2019-12-06 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::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::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::Spinocerebellar ataxia type 1 (SCA1) is a lethal, autosomal dominant neurodegenerative disease caused by a polyglutamine expansion in the ATAXIN-1 (ATXN1) protein. Preclinical studies demonstrate the therapeutic efficacy of approaches that target and reduce Atxn1 expression in a non-allele-specific manner. However, st...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章
doi:10.1016/j.omtn.2020.07.030
更新日期:2020-09-04 00:00:00
abstract::Clec4a has been reported to be an immune suppressor of dendritic cells (DCs), but its potential role in cancer therapy remains to be elucidated. The present study investigated whether downregulating the expression of Clec4a via skin delivery of small hairpin RNA (shRNA) using a gene gun produced stronger host immunity...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章
doi:10.1016/j.omtn.2017.10.015
更新日期:2017-12-15 00:00:00
abstract::F-box and WD repeat domain-containing protein 7 (FBW7) has been documented to be implicated in nuclear factor κB (NF-κB) signaling and inflammation, but its role in the pathogenesis of inflammatory bowel disease (IBD) remains unknown. FBW7 was increased both in colon tissues from IBD patients and trinitrobenzene sulph...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章
doi:10.1016/j.omtn.2019.10.048
更新日期:2020-03-06 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::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::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::Schizophrenia (SCZ) is a devastating genetic mental disorder. Identification of the SCZ risk genes in brains is helpful to understand this disease. Thus, we first used the minimum Redundancy-Maximum Relevance (mRMR) approach to integrate the genome-wide sequence analysis results on SCZ and the expression quantitative ...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章
doi:10.1016/j.omtn.2018.05.026
更新日期:2018-09-07 00:00:00
abstract::Inflammatory mediators play a key role in the pathogenesis of acute respiratory distress syndrome (ARDS). In this study, we aimed to explore the involvement of the Kcnq1 opposite strand/antisense transcript 1 (Kcnq1ot1)/miR-381-3p/E26 transformation-specific proto-oncogene 2 (ETS2) axis in inflammation of lipopolysacc...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章
doi:10.1016/j.omtn.2019.10.036
更新日期:2020-03-06 00:00:00
abstract::MicroRNA (miR)-137 is highly expressed in the brain and plays a crucial role in the development and prognosis of glioma. In this review, we aim to summarize the latest findings regarding miR-137 in glioma cell apoptosis, proliferation, migration, invasion, angiogenesis, drug resistance, and cancer treatment. In additi...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章,评审
doi:10.1016/j.omtn.2020.06.028
更新日期:2020-09-04 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::Retinoic acid-inducible gene-I (RIG-I) is a cytosolic pathogen sensor that is crucial against a number of viral infections. Many viruses have evolved to inhibit pathogen sensors to suppress host innate immune responses. In the case of influenza, nonstructural protein 1 (NS1) suppresses RIG-I function, leading to viral...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章
doi:10.1016/j.omtn.2020.01.025
更新日期:2020-03-06 00:00:00
abstract::E-selectin is an adhesion molecule expressed on the luminal surface of inflamed blood vessels that mediates hematogenous metastasis by assisting shear-resistant adhesion of circulating tumor cells to the vessel surface under dynamic blood flow. Previously, we developed an E-selectin antagonistic thioaptamer (ESTA) for...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章
doi:10.1038/mtna.2016.103
更新日期:2016-12-13 00:00:00
abstract::Septic shock with heart dysfunction is very common in intensive care units. However, whether long noncoding RNA (lncRNA) and mRNA profiles differ between patients with and without myocardial depression is unknown. We generated rat models of hypodynamic septic shock induced by lipopolysaccharide. A total of 12 rat mode...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章
doi:10.1016/j.omtn.2019.07.020
更新日期:2019-09-06 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::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::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::Colon cancer is one of the most common malignancies causing death worldwide. It is well known that the cells of the tumor microenvironment contribute to the progression and prognosis of colon cancer. However, the gene alterations and potential remodeling mechanisms in the tumor microenvironment of colon cancer remain ...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章
doi:10.1016/j.omtn.2020.08.029
更新日期:2020-08-29 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::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::Pancreatic cancer is characterized by chemoresistance after several cycles of chemotherapy, which is a major issue responsible for treatment failure of pancreatic cancer. Therefore, it is necessary to explore the specific mechanism underlying chemotherapeutic resistance to overcome this issue. Here we report that miR-...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章
doi:10.1016/j.omtn.2018.01.004
更新日期:2018-06-01 00:00:00
abstract::Next-generation sequencing technology has been commonly applied to detect mitochondrial DNA (mtDNA) mutations, which are reported to be strongly associated with cancers. However, several key challenges still exist regarding bioinformatics analysis of mtDNA sequencing data that greatly affect the detection accuracy of ...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章
doi:10.1016/j.omtn.2020.11.002
更新日期:2020-11-11 00:00:00
abstract::Novel nanoscale bioconjugates combining unique plasmonic photothermal properties of gold nanoparticles (AuNPs) with targeted delivery using cell-specific DNA aptamers have a tremendous potential for medical diagnostics and therapy of many cell-based diseases. In this study, we demonstrate the high anti-cancer activity...
journal_title:Molecular therapy. Nucleic acids
pub_type: 杂志文章
doi:10.1016/j.omtn.2017.08.007
更新日期:2017-12-15 00:00:00