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Therapeutic potential of FLANC, a novel primate-specific long non-coding RNA in colorectal cancer

The result's identifiers

  • Result code in IS VaVaI

    <a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00209805%3A_____%2F20%3A00078485" target="_blank" >RIV/00209805:_____/20:00078485 - isvavai.cz</a>

  • Alternative codes found

    RIV/00216224:14740/20:00118365

  • Result on the web

    <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7382985/pdf/nihms-1594904.pdf" target="_blank" >https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7382985/pdf/nihms-1594904.pdf</a>

  • DOI - Digital Object Identifier

    <a href="http://dx.doi.org/10.1136/gutjnl-2019-318903" target="_blank" >10.1136/gutjnl-2019-318903</a>

Alternative languages

  • Result language

    angličtina

  • Original language name

    Therapeutic potential of FLANC, a novel primate-specific long non-coding RNA in colorectal cancer

  • Original language description

    Objective To investigate the function of a novel primate-specific long non-coding RNA (lncRNA), named FLANC, based on its genomic location (co-localised with a pyknon motif), and to characterise its potential as a biomarker and therapeutic target. Design FLANC expression was analysed in 349 tumours from four cohorts and correlated to clinical data. In a series of multiple in vitro and in vivo models and molecular analyses, we characterised the fundamental biological roles of this lncRNA. We further explored the therapeutic potential of targeting FLANC in a mouse model of colorectal cancer (CRC) metastases. Results FLANC, a primate-specific lncRNA feebly expressed in normal colon cells, was significantly upregulated in cancer cells compared with normal colon samples in two independent cohorts. High levels of FLANC were associated with poor survival in two additional independent CRC patient cohorts. Both in vitro and in vivo experiments demonstrated that the modulation of FLANC expression influenced cellular growth, apoptosis, migration, angiogenesis and metastases formation ability of CRC cells. In vivo pharmacological targeting of FLANC by administration of 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine nanoparticles loaded with a specific small interfering RNA, induced significant decrease in metastases, without evident tissue toxicity or pro-inflammatory effects. Mechanistically, FLANC upregulated and prolonged the half-life of phosphorylated STAT3, inducing the overexpression of VEGFA, a key regulator of angiogenesis. Conclusions Based on our findings, we discovered, FLANC as a novel primate-specific lncRNA that is highly upregulated in CRC cells and regulates metastases formation. Targeting primate-specific transcripts such as FLANC may represent a novel and low toxic therapeutic strategy for the treatment of patients.

  • Czech name

  • Czech description

Classification

  • Type

    J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database

  • CEP classification

  • OECD FORD branch

    30204 - Oncology

Result continuities

  • Project

  • Continuities

    I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Others

  • Publication year

    2020

  • Confidentiality

    S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Data specific for result type

  • Name of the periodical

    Gut

  • ISSN

    0017-5749

  • e-ISSN

  • Volume of the periodical

    69

  • Issue of the periodical within the volume

    10

  • Country of publishing house

    GB - UNITED KINGDOM

  • Number of pages

    14

  • Pages from-to

    1818-1831

  • UT code for WoS article

    000572338600017

  • EID of the result in the Scopus database

    2-s2.0-85078936713