MSC-Derived Exosomes Protect Vertebral Endplate Chondrocytes against Apoptosis and Calcification via the miR-31-5p/ATF6 Axis.

Abstract:

:Apoptosis and calcification of endplate chondrocytes (EPCs) can exacerbate intervertebral disc degeneration (IVDD). Mesenchymal stem cell-derived exosomes (MSC-exosomes) are reported to have the therapeutic potential in IVDD. However, the effects and related mechanisms of MSC-exosomes on EPCs are still unclear. We aimed to investigate the role of MSC-exosomes on EPCs with a tert-butyl hydroperoxide (TBHP)-induced oxidative stress cell model and IVDD rat model. First, our study revealed that TBHP could result in apoptosis and calcification of EPCs, and MSC-exosomes could inhibit the detrimental effects. We also found that these protective effects were inhibited after miroRNA (miR)-31-5p levels were downregulated in MSC-exosomes. The target relationship between miR-31-5p and ATF6 was tested. miR-31-5p negatively regulated ATF6-related endoplasmic reticulum (ER) stress and inhibited apoptosis and calcification in EPCs. Our in vivo experiments indicated that sub-endplate injection of MSC-exosomes can ameliorate IVDD; however, after miR-31-5p levels were downregulated in MSC-exosomes, these protective effects were inhibited. In conclusion, MSC-exosomes reduced apoptosis and calcification in EPCs, and the underlying mechanism may be related to miR-31-5p/ATF6/ER stress pathway regulation.

journal_name

Mol Ther Nucleic Acids

authors

Xie L,Chen Z,Liu M,Huang W,Zou F,Ma X,Tao J,Guo J,Xia X,Lyu F,Wang H,Zheng C,Jiang J

doi

10.1016/j.omtn.2020.09.026

subject

Has Abstract

pub_date

2020-09-26 00:00:00

pages

601-614

issn

2162-2531

pii

S2162-2531(20)30297-3

journal_volume

22

pub_type

杂志文章
  • Notch-1 Confers Chemoresistance in Lung Adenocarcinoma to Taxanes through AP-1/microRNA-451 Mediated Regulation of MDR-1.

    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

    authors: Huang J,Chen Y,Li J,Zhang K,Chen J,Chen D,Feng B,Song H,Feng J,Wang R,Chen L

    更新日期:2016-10-11 00:00:00

  • Activating PTEN Tumor Suppressor Expression with the CRISPR/dCas9 System.

    abstract::PTEN expression is lost in many cancers, and even small changes in PTEN activity affect susceptibility and prognosis in a range of highly aggressive malignancies, such as melanoma and triple-negative breast cancer (TNBC). Loss of PTEN expression occurs via multiple mechanisms, including mutation, transcriptional repre...

    journal_title:Molecular therapy. Nucleic acids

    pub_type: 杂志文章

    doi:10.1016/j.omtn.2018.12.003

    authors: Moses C,Nugent F,Waryah CB,Garcia-Bloj B,Harvey AR,Blancafort P

    更新日期:2019-03-01 00:00:00

  • Mir-34: a new weapon against cancer?

    abstract::The microRNA(miRNA)-34a is a key regulator of tumor suppression. It controls the expression of a plethora of target proteins involved in cell cycle, differentiation and apoptosis, and antagonizes processes that are necessary for basic cancer cell viability as well as cancer stemness, metastasis, and chemoresistance. I...

    journal_title:Molecular therapy. Nucleic acids

    pub_type: 杂志文章,评审

    doi:10.1038/mtna.2014.47

    authors: Misso G,Di Martino MT,De Rosa G,Farooqi AA,Lombardi A,Campani V,Zarone MR,Gullà A,Tagliaferri P,Tassone P,Caraglia M

    更新日期:2014-09-23 00:00:00

  • The Circular RNA-miRNA Axis: A Special RNA Signature Regulatory Transcriptome as a Potential Biomarker for OSCC.

    abstract::Oral squamous cell carcinoma (OSCC) is a highly recurrent form of cancer arising from the oral epithelium, which is the result of mutational change due to etiological factors such as tobacco, smoking, chewing of areca nuts, and alcohol consumption. OSCC occurrence has been observed to be prevalent in different regions...

    journal_title:Molecular therapy. Nucleic acids

    pub_type: 杂志文章,评审

    doi:10.1016/j.omtn.2020.09.001

    authors: Saikishore R,Velmurugan P,Ranjithkumar D,Latha R,Sathiamoorthi T,Arun A,Ravi AV,Sivakumar S

    更新日期:2020-09-06 00:00:00

  • Identification of Novel Tumor-Microenvironment-Regulating Factor That Facilitates Tumor Immune Infiltration in Colon Cancer.

    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

    authors: Wang Y,Wang Y,Xu C,Liu Y,Huang Z

    更新日期:2020-08-29 00:00:00

  • Mathematical Modeling: A Tool for Optimization of Lipid Nanoparticle-Mediated Delivery of siRNA.

    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

    authors: Mihaila R,Ruhela D,Keough E,Cherkaev E,Chang S,Galinski B,Bartz R,Brown D,Howell B,Cunningham JJ

    更新日期:2017-06-16 00:00:00

  • Targeted suicide gene therapy for liver cancer based on ribozyme-mediated RNA replacement through post-transcriptional regulation.

    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

    authors: Han SR,Lee CH,Im JY,Kim JH,Kim JH,Kim SJ,Cho YW,Kim E,Kim Y,Ryu JH,Ju MH,Jeong JS,Lee SW

    更新日期:2020-10-31 00:00:00

  • miR-582-3p and miR-582-5p Suppress Prostate Cancer Metastasis to Bone by Repressing TGF-β Signaling.

    abstract::A number of studies have reported that aberrant expression of microRNAs (miRNAs) closely correlates with the bone metastasis of prostate cancer (PCa). However, clinical significance and functional roles of both strands of a single miRNA in bone metastasis of PCa remain undefined. Here, we reported that miR-582-3p and ...

    journal_title:Molecular therapy. Nucleic acids

    pub_type: 杂志文章

    doi:10.1016/j.omtn.2019.01.004

    authors: Huang S,Zou C,Tang Y,Wa Q,Peng X,Chen X,Yang C,Ren D,Huang Y,Liao Z,Huang S,Zou X,Pan J

    更新日期:2019-06-07 00:00:00

  • N6-Adenosine Methylation of miRNA-200b-3p Influences Its Functionality and Is a Theranostic Tool.

    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

    authors: Briand J,Sérandour AA,Nadaradjane A,Bougras-Cartron G,Heymann D,Ory B,Vallette FM,Cartron PF

    更新日期:2020-08-14 00:00:00

  • LncRNA TRERNA1 Function as an Enhancer of SNAI1 Promotes Gastric Cancer Metastasis by Regulating Epithelial-Mesenchymal Transition.

    abstract::Long noncoding RNA (lncRNA) has been implicated in cancer, but little is known about the role of lncRNAs as regulators of tumor metastasis. In the present study, we demonstrate that lncRNA TRERNA1 acts like an enhancer of SNAI1 to promote cell invasion and migration and to contribute to metastasis of gastric cancer (G...

    journal_title:Molecular therapy. Nucleic acids

    pub_type: 杂志文章

    doi:10.1016/j.omtn.2017.06.021

    authors: Wu H,Hu Y,Liu X,Song W,Gong P,Zhang K,Chen Z,Zhou M,Shen X,Qian Y,Fan H

    更新日期:2017-09-15 00:00:00

  • An innovative data analysis strategy for accurate next-generation sequencing detection of tumor mitochondrial DNA mutations.

    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

    authors: Guo S,Zhou K,Yuan Q,Su L,Liu Y,Ji X,Gu X,Guo X,Xing J

    更新日期:2020-11-11 00:00:00

  • Progress in RNAi-mediated Molecular Therapy of Acute and Chronic Myeloid Leukemia.

    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

    authors: Landry B,Valencia-Serna J,Gul-Uludag H,Jiang X,Janowska-Wieczorek A,Brandwein J,Uludag H

    更新日期:2015-05-12 00:00:00

  • Molecular Signatures and Networks of Cardiomyocyte Differentiation in Humans and Mice.

    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

    authors: Wang Y,Yi N,Hu Y,Zhou X,Jiang H,Lin Q,Chen R,Liu H,Gu Y,Tong C,Lu M,Zhang J,Zhang B,Peng L,Li L

    更新日期:2020-09-04 00:00:00

  • NLRP3 Inflammasome Activation by MicroRNA-495 Promoter Methylation May Contribute to the Progression of Acute Lung Injury.

    abstract::Acute lung injury (ALI) is a pulmonary disorder that causes acute respiratory failure, thus leading to relative high mortality worldwide. However, the molecular mechanisms of ALI remain largely unknown. MicroRNA (miRNA)-dependent control of gene expression at a post-transcriptional level has been recently reported. He...

    journal_title:Molecular therapy. Nucleic acids

    pub_type: 杂志文章

    doi:10.1016/j.omtn.2019.08.028

    authors: Ying Y,Mao Y,Yao M

    更新日期:2019-12-06 00:00:00

  • Cross-Species Suppression of Hepatoma Cell Growth and Migration by a Schistosoma japonicum MicroRNA.

    abstract::Schistosoma japonicum eggs trapped in host liver secretes microRNA (miRNA)-containing extracellular vesicles (EVs) that can be transferred to host cells. Recent studies demonstrated that miRNAs derived from plants can modulate gene expression and phenotype of mammalian cells in a cross-kingdom manner. In this study, w...

    journal_title:Molecular therapy. Nucleic acids

    pub_type: 杂志文章

    doi:10.1016/j.omtn.2019.09.006

    authors: Lin Y,Zhu S,Hu C,Wang J,Jiang P,Zhu L,Li Z,Wang S,Zhang Y,Xu X,Pan W

    更新日期:2019-12-06 00:00:00

  • The Underlying Mechanisms of Noncoding RNAs in the Chemoresistance of Hepatocellular Carcinoma.

    abstract::Hepatocellular carcinoma (HCC) is one of the most lethal human malignancies. Chemotherapeutic agents, such as sorafenib and lenvatinib, can improve the outcomes of HCC patients. Nevertheless, chemoresistance has become a major hurdle in the effective treatment of HCC. Noncoding RNAs (ncRNAs), including mircoRNAs (miRN...

    journal_title:Molecular therapy. Nucleic acids

    pub_type: 杂志文章,评审

    doi:10.1016/j.omtn.2020.05.011

    authors: Wang M,Yu F,Chen X,Li P,Wang K

    更新日期:2020-09-04 00:00:00

  • Circular RNA circTNPO3 Regulates Paclitaxel Resistance of Ovarian Cancer Cells by miR-1299/NEK2 Signaling Pathway.

    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

    authors: Xia B,Zhao Z,Wu Y,Wang Y,Zhao Y,Wang J

    更新日期:2020-09-04 00:00:00

  • Targeting Nicotinamide N-Methyltransferase and miR-449a in EGFR-TKI-Resistant Non-Small-Cell Lung Cancer Cells.

    abstract::Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are used clinically as target therapies for lung cancer patients, but the occurrence of acquired drug resistance limits their efficacy. Nicotinamide N-methyltransferase (NNMT), a cancer-associated metabolic enzyme, is commonly overexpressed in var...

    journal_title:Molecular therapy. Nucleic acids

    pub_type: 杂志文章

    doi:10.1016/j.omtn.2018.03.011

    authors: Bach DH,Kim D,Bae SY,Kim WK,Hong JY,Lee HJ,Rajasekaran N,Kwon S,Fan Y,Luu TT,Shin YK,Lee J,Lee SK

    更新日期:2018-06-01 00:00:00

  • Circulating lncRNA UCA1 Promotes Malignancy of Colorectal Cancer via the miR-143/MYO6 Axis.

    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

    authors: Luan Y,Li X,Luan Y,Zhao R,Li Y,Liu L,Hao Y,Oleg Vladimir B,Jia L

    更新日期:2020-03-06 00:00:00

  • MSTN Attenuates Cardiac Hypertrophy through Inhibition of Excessive Cardiac Autophagy by Blocking AMPK /mTOR and miR-128/PPARγ/NF-κB.

    abstract::Cardiac hypertrophy, a response of the heart to increased workload, is a major risk factor for heart failure. Myostatin (MSTN) is an inhibitor of myogenesis, regulating the number and size of skeletal myocytes. In recent years, cardiomyocyte autophagy also has been considered to be involved in controlling the hypertro...

    journal_title:Molecular therapy. Nucleic acids

    pub_type: 杂志文章

    doi:10.1016/j.omtn.2019.12.003

    authors: Qi H,Ren J,Ba L,Song C,Zhang Q,Cao Y,Shi P,Fu B,Liu Y,Sun H

    更新日期:2020-03-06 00:00:00

  • Expanding the Repertoire of Target Sites for Zinc Finger Nuclease-mediated Genome Modification.

    abstract::Recent studies have shown that zinc finger nucleases (ZFNs) are powerful reagents for making site-specific genomic modifications. The generic structure of these enzymes includes a ZF DNA-binding domain and nuclease domain (Fn) are separated by an amino acid "linker" and cut genomic DNA at sites that have a generic str...

    journal_title:Molecular therapy. Nucleic acids

    pub_type: 杂志文章

    doi:10.1038/mtna.2013.13

    authors: Wilson KA,McEwen AE,Pruett-Miller SM,Zhang J,Kildebeck EJ,Porteus MH

    更新日期:2013-04-30 00:00:00

  • Activation of Fetal γ-globin Gene Expression via Direct Protein Delivery of Synthetic Zinc-finger DNA-Binding Domains.

    abstract::Reactivation of γ-globin expression has been shown to ameliorate disease phenotypes associated with mutations in the adult β-globin gene, including sickle cell disease. Specific mutations in the promoter of the γ-globin genes are known to prevent repression of the genes in the adult and thus lead to hereditary persist...

    journal_title:Molecular therapy. Nucleic acids

    pub_type: 杂志文章

    doi:10.1038/mtna.2016.85

    authors: Hossain MA,Shen Y,Knudson I,Thakur S,Stees JR,Qiu Y,Pace BS,Peterson KR,Bungert J

    更新日期:2016-10-18 00:00:00

  • The Processing, Gene Regulation, Biological Functions, and Clinical Relevance of N4-Acetylcytidine on RNA: A Systematic Review.

    abstract::N4-acetylcytidine (ac4C) is often considered to be a conservative, chemically modified nucleoside present on tRNA and rRNA. Recent studies have shown extensive ac4C modifications in human and yeast mRNAs. ac4C helps to correctly read codons during translation and improves translation efficiency and the stability of mR...

    journal_title:Molecular therapy. Nucleic acids

    pub_type: 杂志文章,评审

    doi:10.1016/j.omtn.2020.01.037

    authors: Jin G,Xu M,Zou M,Duan S

    更新日期:2020-06-05 00:00:00

  • Overexpressed lncRNA GATA6-AS1 Inhibits LNM and EMT via FZD4 through the Wnt/β-Catenin Signaling Pathway in GC.

    abstract::Gastric cancer (GC) is one of the leading causes of cancer-related deaths worldwide. Accumulating evidence reveals the significance of long non-coding RNAs (lncRNAs) in various cancers. The current study aimed to evaluate the role of GATA6 antisense RNA 1 (GATA6-AS1) in the epithelial-mesenchymal transition (EMT) and ...

    journal_title:Molecular therapy. Nucleic acids

    pub_type: 杂志文章

    doi:10.1016/j.omtn.2019.09.034

    authors: Li ZT,Zhang X,Wang DW,Xu J,Kou KJ,Wang ZW,Yong G,Liang DS,Sun XY

    更新日期:2020-03-06 00:00:00

  • Enhanced Tailored MicroRNA Sponge Activity of RNA Pol II-Transcribed TuD Hairpins Relative to Ectopically Expressed ciRS7-Derived circRNAs.

    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

    authors: Hollensen AK,Andersen S,Hjorth K,Bak RO,Hansen TB,Kjems J,Aagaard L,Damgaard CK,Mikkelsen JG

    更新日期:2018-12-07 00:00:00

  • VPS33B modulates c-Myc/p53/miR-192-3p to target CCNB1 suppressing the growth of non-small cell lung cancer.

    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

    authors: Liu J,Wen Y,Liu Z,Liu S,Xu P,Xu Y,Deng S,Hu S,Luo R,Jiang J,Yu G

    更新日期:2020-11-17 00:00:00

  • Dose-Finding Study and Pharmacokinetics Profile of the Novel 13-Mer Antisense miR-221 Inhibitor in Sprague-Dawley Rats.

    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

    authors: Di Martino MT,Arbitrio M,Caracciolo D,Scionti F,Tagliaferri P,Tassone P

    更新日期:2020-06-05 00:00:00

  • Identifying Involvement of H19-miR-675-3p-IGF1R and H19-miR-200a-PDCD4 in Treating Pulmonary Hypertension with Melatonin.

    abstract::Non-coding RNAs play an important role in the pathogenesis of pulmonary arterial hypertension (PAH). The aim of this study was to characterize the therapeutic role of melatonin as well as the underlying molecular mechanism (its effects on the expression of H19 and its downstream signaling pathways) in the treatment of...

    journal_title:Molecular therapy. Nucleic acids

    pub_type: 杂志文章

    doi:10.1016/j.omtn.2018.08.015

    authors: Wang R,Zhou S,Wu P,Li M,Ding X,Sun L,Xu X,Zhou X,Zhou L,Cao C,Fei G

    更新日期:2018-12-07 00:00:00

  • TALENs Facilitate Single-step Seamless SDF Correction of F508del CFTR in Airway Epithelial Submucosal Gland Cell-derived CF-iPSCs.

    abstract::Cystic fibrosis (CF) is a recessive inherited disease associated with multiorgan damage that compromises epithelial and inflammatory cell function. Induced pluripotent stem cells (iPSCs) have significantly advanced the potential of developing a personalized cell-based therapy for diseases like CF by generating patient...

    journal_title:Molecular therapy. Nucleic acids

    pub_type: 杂志文章

    doi:10.1038/mtna.2015.43

    authors: Suzuki S,Sargent RG,Illek B,Fischer H,Esmaeili-Shandiz A,Yezzi MJ,Lee A,Yang Y,Kim S,Renz P,Qi Z,Yu J,Muench MO,Beyer AI,Guimarães AO,Ye L,Chang J,Fine EJ,Cradick TJ,Bao G,Rahdar M,Porteus MH,Shuto T,Kai H,

    更新日期:2016-01-05 00:00:00

  • Mitochondrial DNA Haplogroup N9a Negatively Correlates with Incidence of Hepatocellular Carcinoma in Northern China.

    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

    authors: Hua S,Li M,Zhao Q,Wang J,Zhou Y,Liu J,Fang H,Jiang M,Shen L

    更新日期:2019-12-06 00:00:00