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Therapeutic potential of FLANC, a novel primate-specific long non-coding RNA in colorectal cancer
M. Pichler, C. Rodriguez-Aguayo, SY. Nam, MP. Dragomir, R. Bayraktar, S. Anfossi, E. Knutsen, C. Ivan, E. Fuentes-Mattei, SK. Lee, H. Ling, T. Catela Ivkovic, G. Huang, L. Huang, Y. Okugawa, H. Katayama, A. Taguchi, E. Bayraktar, R. Bhattacharya,...
Jazyk angličtina Země Velká Británie
Typ dokumentu časopisecké články, Research Support, N.I.H., Extramural, práce podpořená grantem, Research Support, U.S. Gov't, Non-P.H.S.
Grantová podpora
U01 CA213759
NCI NIH HHS - United States
U54 CA210181
NCI NIH HHS - United States
U54 CA096297
NCI NIH HHS - United States
UH3 TR000943
NCATS NIH HHS - United States
R01 CA184792
NCI NIH HHS - United States
U01 CA187956
NCI NIH HHS - United States
U54 CA096300
NCI NIH HHS - United States
U01 CA196403
NCI NIH HHS - United States
R01 CA181572
NCI NIH HHS - United States
R01 CA072851
NCI NIH HHS - United States
R01 CA182905
NCI NIH HHS - United States
P30 CA016672
NCI NIH HHS - United States
R01 CA222007
NCI NIH HHS - United States
R01 CA226537
NCI NIH HHS - United States
R01 GM122775
NIGMS NIH HHS - United States
NLK
ProQuest Central
od 1960-03-01 do Před 6 měsíci
Health & Medicine (ProQuest)
od 1960-03-01 do Před 6 měsíci
- MeSH
- farmakogenomické testování MeSH
- genetická terapie MeSH
- genetické markery MeSH
- karcinogeneze * účinky léků genetika MeSH
- kolorektální nádory * genetika terapie MeSH
- lidé MeSH
- myši MeSH
- nádorové biomarkery genetika metabolismus MeSH
- objevování léků MeSH
- patologická angiogeneze * genetika metabolismus MeSH
- proliferace buněk * účinky léků genetika MeSH
- regulace genové exprese u nádorů MeSH
- RNA dlouhá nekódující * genetika metabolismus MeSH
- transkripční faktor STAT3 metabolismus MeSH
- vaskulární endoteliální růstový faktor A metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
- Research Support, U.S. Gov't, Non-P.H.S. MeSH
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.
Central European Institute of Technology Masaryk University Brno Czech Republic
Department of Cancer Biology University of Texas MD Anderson Cancer Center Houston Texas USA
Department of Comprehensive Cancer Care Masaryk Memorial Cancer Institute Brno Czech Republic
Department of Medical Sciences University of Ferrara Ferrara Emilia Romagna Italy
Department of Surgery Dubrava Clinical Hospital Zagreb Croatia
Department of Surgical Oncology University of Texas MD Anderson Cancer Center Houston Texas USA
Division of Molecular Medicine Ruder Boskovic Institute Zagreb Croatia
Division of Oncology Medical University of Graz Graz Styria Austria
Gastroenterology Department Kyungpook National University Hospital
Mathematics in Medicine Program The Houston Methodist Research Institute Houston Texas USA
Medical and Molecular Genetics Department Indiana University Indianapolis Indiana USA
School of Medicine Kyungpook National University Daegu South Korea
Citace poskytuje Crossref.org
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