Long Non-Coding RNA PANTR1 is Associated with Poor Prognosis
and Influences Angiogenesis and Apoptosis in Clear-Cell Renal
Cell Cancer

J 2020

Long Non-Coding RNA PANTR1 is Associated with Poor Prognosis and Influences Angiogenesis and Apoptosis in Clear-Cell Renal Cell Cancer

SELES, M.; G. C. HUTTERER; J. FOSSELTEDER; Marek SVOBODA; M. RESEL et al.

Základní údaje

Originální název

Long Non-Coding RNA PANTR1 is Associated with Poor Prognosis and Influences Angiogenesis and Apoptosis in Clear-Cell Renal Cell Cancer

Autoři

SELES, M.; G. C. HUTTERER; J. FOSSELTEDER; Marek SVOBODA; M. RESEL; D. A. BARTH; R. PICHLER; T. BAUERNHOFER; R. E. ZIGEUNER; K. PUMMER; Ondřej SLABÝ; C. KLEC a M. PICHLER

Vydání

Cancers, BASEL, MDPI, 2020, 2072-6694

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30204 Oncology

Stát vydavatele

Švýcarsko

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 6.639

Označené pro přenos do RIV

Ano

Kód RIV

RIV/00216224:14740/20:00118647

Organizační jednotka

Středoevropský technologický institut

Klíčová slova anglicky

long intergenic non-coding RNA; PANTR1; Linc01158; Linc-POU3F3; siRNA; renal cell cancer; clear-cell renal cell carcinoma; oncogene

Štítky

14110513, podil, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 26. 4. 2021 13:47, Mgr. Tereza Miškechová

Anotace

V originále

POU3F3 adjacent non-coding transcript 1 (PANTR1) is an oncogenic long non-coding RNA with significant influence on numerous cellular features in different types of cancer. No characterization of its role in renal cell carcinoma (RCC) is yet available. In this study, PANTR1 expression was confined to human brain and kidney tissue and was found significantly up-regulated in clear-cell renal cell carcinoma tissue (ccRCC) compared to non-cancerous kidney tissue in two independent cohorts (p < 0.001 for both cohorts). In uni- and multivariate Cox regression analysis, ccRCC patients with higher levels of PANTR1 showed significantly poorer disease-free survival in our own respective cohort (n = 175, hazard ratio: 4.3, 95% confidence interval: 1.45-12.75, p = 0.008) in accordance with significantly poorer overall survival in a large The Cancer Genome Atlas database (TCGA) cohort (n = 530, hazard ratio: 2.19, 95% confidence interval: 1.59-3.03, p 0.001). To study the underlying cellular mechanisms mediated by varying levels of PANTR1 in kidney cancer cells, we applied siRNA-mediated knock-down experiments in three independent ccRCC cell lines (RCC-FG, RCC-MF, 769-P). A decrease in PANTR1 levels led to significantly reduced cellular growth through activation of apoptosis in all tested cell lines. Moreover, as angiogenesis is a critical driver in ccRCC pathogenesis, we identified that PANTR1 expression is critical for in vitro tube formation and endothelial cell migration (p < 0.05). On the molecular level, knock-down of PANTR1 led to a decrease in Vascular Endothelial growth factor A (VEGF-A) and cell adhesion molecule laminin subunit gamma-2 (LAMC2) expression, corroborated by a positive correlation in RCC tissue (for VEGF-A R = 0.19, p < 0.0001, for LAMC2 R = 0.13, p = 0.0028). In conclusion, this study provides first evidence that PANTR1 has a relevant role in human RCC by influencing apoptosis and angiogenesis.

Návaznosti

NV18-03-00554, projekt VaV

Název: Molekulární klasifikace renálního buněčného karcinomu založená na expresi dlouhých nekódujících RNA a její využití v diagnostice, předpovědi prognózy a terapii

Investor: Ministerstvo zdravotnictví ČR, Molecular classification of renal cell carcinoma based on long noncoding RNAs expression and its implication for diagnosis, prognosis and therapy

824036, interní kód MU

Název: Excellence in research and development of non-coding RNA DIAGnostics in ONcology (Akronym: RNADIAGON)

Investor: Evropská unie, Excellence in research and development of non-coding RNA DIAGnostics in ONcology, MSCA Marie Skłodowska-Curie Actions (Excellent Science)

90125, velká výzkumná infrastruktura

Název: BBMRI-CZ III

Přiložené soubory

cancers-12-01200-v2.pdf

Citovat

SELES, M.; G. C. HUTTERER; J. FOSSELTEDER; Marek SVOBODA; M. RESEL; D. A. BARTH; R. PICHLER; T. BAUERNHOFER; R. E. ZIGEUNER; K. PUMMER; Ondřej SLABÝ; C. KLEC a M. PICHLER. Long Non-Coding RNA PANTR1 is Associated with Poor Prognosis and Influences Angiogenesis and Apoptosis in Clear-Cell Renal Cell Cancer. Cancers. BASEL: MDPI, 2020, roč. 12, č. 5, s. 1-17. ISSN 2072-6694. Dostupné z: https://doi.org/10.3390/cancers12051200.

@article{1744865,
   author = {Seles, M. and Hutterer, G. C. and Fosselteder, J. and Svoboda, Marek and Resel, M. and Barth, D. A. and Pichler, R. and Bauernhofer, T. and Zigeuner, R. E. and Pummer, K. and Slabý, Ondřej and Klec, C. and Pichler, M.},
   article_location = {BASEL},
   article_number = {5},
   doi = {https://doi.org/10.3390/cancers12051200},
   keywords = {long intergenic non-coding RNA; PANTR1; Linc01158; Linc-POU3F3; siRNA; renal cell cancer; clear-cell renal cell carcinoma; oncogene},
   language = {eng},
   issn = {2072-6694},
   journal = {Cancers},
   title = {Long Non-Coding RNA PANTR1 is Associated with Poor Prognosis and Influences Angiogenesis and Apoptosis in Clear-Cell Renal Cell Cancer},
   url = {https://www.mdpi.com/2072-6694/12/5/1200},
   volume = {12},
   year = {2020}
}

TY  - JOUR
ID  - 1744865
AU  - Seles, M. - Hutterer, G. C. - Fosselteder, J. - Svoboda, Marek - Resel, M. - Barth, D. A. - Pichler, R. - Bauernhofer, T. - Zigeuner, R. E. - Pummer, K. - Slabý, Ondřej - Klec, C. - Pichler, M.
PY  - 2020
TI  - Long Non-Coding RNA PANTR1 is Associated with Poor Prognosis and Influences Angiogenesis and Apoptosis in Clear-Cell Renal Cell Cancer
JF  - Cancers
VL  - 12
IS  - 5
SP  - 1-17
EP  - 1-17
PB  - MDPI
SN  - 20726694
KW  - long intergenic non-coding RNA
KW  - PANTR1
KW  - Linc01158
KW  - Linc-POU3F3
KW  - siRNA
KW  - renal cell cancer
KW  - clear-cell renal cell carcinoma
KW  - oncogene
UR  - https://www.mdpi.com/2072-6694/12/5/1200
N2  - POU3F3 adjacent non-coding transcript 1 (PANTR1) is an oncogenic long non-coding RNA with significant influence on numerous cellular features in different types of cancer. No characterization of its role in renal cell carcinoma (RCC) is yet available. In this study, PANTR1 expression was confined to human brain and kidney tissue and was found significantly up-regulated in clear-cell renal cell carcinoma tissue (ccRCC) compared to non-cancerous kidney tissue in two independent cohorts (p < 0.001 for both cohorts). In uni- and multivariate Cox regression analysis, ccRCC patients with higher levels of PANTR1 showed significantly poorer disease-free survival in our own respective cohort (n = 175, hazard ratio: 4.3, 95% confidence interval: 1.45-12.75, p = 0.008) in accordance with significantly poorer overall survival in a large The Cancer Genome Atlas database (TCGA) cohort (n = 530, hazard ratio: 2.19, 95% confidence interval: 1.59-3.03, p 0.001). To study the underlying cellular mechanisms mediated by varying levels of PANTR1 in kidney cancer cells, we applied siRNA-mediated knock-down experiments in three independent ccRCC cell lines (RCC-FG, RCC-MF, 769-P). A decrease in PANTR1 levels led to significantly reduced cellular growth through activation of apoptosis in all tested cell lines. Moreover, as angiogenesis is a critical driver in ccRCC pathogenesis, we identified that PANTR1 expression is critical for in vitro tube formation and endothelial cell migration (p < 0.05). On the molecular level, knock-down of PANTR1 led to a decrease in Vascular Endothelial growth factor A (VEGF-A) and cell adhesion molecule laminin subunit gamma-2 (LAMC2) expression, corroborated by a positive correlation in RCC tissue (for VEGF-A R = 0.19, p < 0.0001, for LAMC2 R = 0.13, p = 0.0028). In conclusion, this study provides first evidence that PANTR1 has a relevant role in human RCC by influencing apoptosis and angiogenesis.
ER  -

SELES, M.; G. C. HUTTERER; J. FOSSELTEDER; Marek SVOBODA; M. RESEL; D. A. BARTH; R. PICHLER; T. BAUERNHOFER; R. E. ZIGEUNER; K. PUMMER; Ondřej SLABÝ; C. KLEC a M. PICHLER. Long Non-Coding RNA PANTR1 is Associated with Poor Prognosis and Influences Angiogenesis and Apoptosis in Clear-Cell Renal Cell Cancer. \textit{Cancers}. BASEL: MDPI, 2020, roč.~12, č.~5, s.~1-17. ISSN~2072-6694. Dostupné z: https://doi.org/10.3390/cancers12051200.

Přehled o publikaci