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
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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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
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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