• Login
    View Item 
    •   Home
    • The Manchester Institute Cancer Research UK
    • All Paterson Institute for Cancer Research
    • View Item
    •   Home
    • The Manchester Institute Cancer Research UK
    • All Paterson Institute for Cancer Research
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Browse

    All of ChristieCommunitiesTitleAuthorsIssue DateSubmit DateSubjectsThis CollectionTitleAuthorsIssue DateSubmit DateSubjects

    My Account

    LoginRegister

    Local Links

    The Christie WebsiteChristie Library and Knowledge Service

    Statistics

    Display statistics

    PDGFR-modulated miR-23b cluster and miR-125a-5p suppress lung tumorigenesis by targeting multiple components of KRAS and NF-kB pathways.

    • CSV
    • RefMan
    • EndNote
    • BibTex
    • RefWorks
    Thumbnail
    Name:
    s41598-017-14843-6.pdf
    Size:
    2.390Mb
    Format:
    PDF
    Description:
    Open access full text article
    Download
    Authors
    Naidu, Srivatsava
    Shi, Lei
    Magee, Peter
    Middleton, J
    Laganá, A
    Sahoo, S
    Leong, H
    Galvin, M
    Frese, K
    Dive, C
    Guzzardo, V
    Fassan, M
    Garofalo, M
    Show allShow less
    Affiliation
    Transcriptional Networks in Lung Cancer Group, Cancer Research UK Manchester Institute, University of Manchester, Manchester, UK
    Issue Date
    2017-11-13
    
    Metadata
    Show full item record
    Abstract
    In NSCLC alterations in PDGF receptors are markers of worst prognosis and efficient targeting of these receptors is yet to be achieved. In this study, we explored PDGFR-regulated microRNAs demonstrating that miR-23b cluster and miR-125a-5p are downregulated by increased expression of PDGFR-α or PDGFR-β in NSCLC cells. Mechanistically, the expression of these microRNAs is positively regulated by p53 and negatively modulated by NF-kB p65. Forced expression of miR-23b cluster or miR-125a-5p enhanced drug sensitivity and suppressed invasiveness of NSCLC cells by silencing several genes involved in oncogenic KRAS and NF-kB pathways, including SOS1, GRB2, IQGAP1, RALA, RAF-1, IKKβ, AKT2, ERK2 and KRAS itself. Of note, an inverse correlation between miR-23b cluster, miR-125a-5p and respective target genes was also found in vivo in a large dataset of lung adenocarcinoma samples. Furthermore, in vivo delivery of miR-23b cluster or miR-125a-5p significantly repressed tumour growth in a highly aggressive NSCLC circulating tumour cell (CTC) patient derived explant (CDX) mouse model. In conclusion, our finding sheds light on the PDGFR signaling and endorses the possibility to employ miR-23b cluster and miR-125a-5p as therapeutic tools to silence simultaneously a range of redundant pathways and main effectors of tumorigenesis in NSCLC.
    Citation
    PDGFR-modulated miR-23b cluster and miR-125a-5p suppress lung tumorigenesis by targeting multiple components of KRAS and NF-kB pathways. 2017, 7 (1):15441 Sci Rep
    Journal
    Scientific Reports
    URI
    http://hdl.handle.net/10541/620719
    DOI
    10.1038/s41598-017-14843-6
    PubMed ID
    29133857
    Type
    Article
    Language
    en
    ISSN
    2045-2322
    ae974a485f413a2113503eed53cd6c53
    10.1038/s41598-017-14843-6
    Scopus Count
    Collections
    All Paterson Institute for Cancer Research

    entitlement

    Related articles

    • Hsa-miR-125a-3p and hsa-miR-125a-5p are downregulated in non-small cell lung cancer and have inverse effects on invasion and migration of lung cancer cells.
    • Authors: Jiang L, Huang Q, Zhang S, Zhang Q, Chang J, Qiu X, Wang E
    • Issue date: 2010 Jun 22
    • Luteolin Inhibits Tumorigenesis and Induces Apoptosis of Non-Small Cell Lung Cancer Cells via Regulation of MicroRNA-34a-5p.
    • Authors: Jiang ZQ, Li MH, Qin YM, Jiang HY, Zhang X, Wu MH
    • Issue date: 2018 Feb 2
    • Reduced miR-125a-5p level in non-small-cell lung cancer is associated with tumour progression.
    • Authors: Liu H, Ma Y, Liu C, Li P, Yu T
    • Issue date: 2018 Oct 10
    • Down-regulation of miR-675-5p contributes to tumor progression and development by targeting pro-tumorigenic GPR55 in non-small cell lung cancer.
    • Authors: He D, Wang J, Zhang C, Shan B, Deng X, Li B, Zhou Y, Chen W, Hong J, Gao Y, Chen Z, Duan C
    • Issue date: 2015 Apr 1
    • The reciprocal regulation loop of Notch2 pathway and miR-23b in controlling gastric carcinogenesis.
    • Authors: Huang TT, Ping YH, Wang AM, Ke CC, Fang WL, Huang KH, Lee HC, Chi CW, Yeh TS
    • Issue date: 2015 Jul 20
    DSpace software (copyright © 2002 - 2021)  DuraSpace
    Quick Guide | Contact Us
    Open Repository is a service operated by 
    Atmire NV
     

    Export search results

    The export option will allow you to export the current search results of the entered query to a file. Different formats are available for download. To export the items, click on the button corresponding with the preferred download format.

    By default, clicking on the export buttons will result in a download of the allowed maximum amount of items.

    To select a subset of the search results, click "Selective Export" button and make a selection of the items you want to export. The amount of items that can be exported at once is similarly restricted as the full export.

    After making a selection, click one of the export format buttons. The amount of items that will be exported is indicated in the bubble next to export format.