MiR-215-5p is a tumor suppressor in colorectal cancer targeting
EGFR ligand epiregulin and its transcriptional inducer HOXB9

J 2017

MiR-215-5p is a tumor suppressor in colorectal cancer targeting EGFR ligand epiregulin and its transcriptional inducer HOXB9

VYCHYTILOVÁ, Petra; Jana MERHAUTOVÁ; Táňa MACHÁČKOVÁ; Irene GUTIERREZ-GARCIA; José GARCIA-SOLANO et. al.

Základní údaje

Originální název

MiR-215-5p is a tumor suppressor in colorectal cancer targeting EGFR ligand epiregulin and its transcriptional inducer HOXB9

Autoři

Vydání

Oncogenesis, New York, USA, Nature publishing group, 2017, 2157-9024

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30200 3.2 Clinical medicine

Stát vydavatele

Spojené státy

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 4.722

Kód RIV

RIV/00216224:14740/17:00095449

Organizační jednotka

Středoevropský technologický institut

DOI

https://doi.org/10.1038/s41389-017-0006-6

UT WoS

000423913000003

EID Scopus

2-s2.0-85036659160

Klíčová slova česky

miR-215; kolorektální karcinom; EGFR; proliferace; nádorový supresor; HOXB9; epiregulin

Klíčová slova anglicky

miR-215; colorectal cancer; EGFR; proliferation; tumor suppressor; HOXB9; epiregulin

Štítky

OA, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 27. 1. 2021 14:47, Mgr. Tereza Miškechová

Anotace

V originále

Growing evidence suggests that microRNAs are involved in the development and progression of colorectal cancer (CRC). In the present study, deregulation and functioning of tumor-suppressive miR-215-5p was evaluated in CRC. In total, 448 tumor tissues and 325 paired adjacent healthy tissues collected from Czech and Spain cohorts of CRC patients have been used for miR-215-5p expression analyses. A series of in vitro experiments have been performed using transient transfection of miR-215-5p mimics into four CRC cell lines to identify specific cellular processes affected by miR-215-5p. Further, the effects of miR-215-5p on tumor growth were evaluated in vivo using NSG mice and stable cell line overexpressing miR-215-5p. Target mRNAs of miR-215-5p were tested using luciferase assay and western blot analyses. We found that miR-215-5p is significantly downregulated in tumor tissues compared with non-tumor adjacent tissues and its decreased levels correlate with the presence of lymph node metastases, tumor stage, and shorter overall survival in CRC patients. Overexpression of miR-215-5p significantly reduced proliferation, clonogenicity, and migration of CRC cells, lead to cell cycle arrest in G2/M phase and p53-dependent induction of apoptosis. The ability of miR-215-5p to inhibit tumor growth was confirmed in vivo. Finally, we confirmed epiregulin and HOXB9 to be the direct targets of miR-215-5p. As epiregulin is EGFR ligand and HOXB9 is its transcriptional inducer, we suggest that the main molecular link between miR-215-5p and CRC cells phenotypes presents the EGFR signaling pathway, which is one of the canonical pathogenic pathways in CRC.

Návaznosti

GA16-18257S, projekt VaV

Název: Studium mechanizmu spojeného s nádorově supresorovou funkcí miR-215 a substituce této miRNA jako nové lečebné strategie u kolorektálního karcinomu

Investor: Grantová agentura ČR, Studium mechanizmu spojeného s nádorově supresorovou funkcí miR-215 a substituce této miRNA jako nové lečebné strategie u kolorektálního karcinomu

LM2015090, projekt VaV

Název: Český národní uzel Evropské sítě infrastruktur klinického výzkumu (Akronym: CZECRIN)

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, CZECRIN - Český národní uzel Evropské sítě infrastruktur klinického výzkumu

LQ1601, projekt VaV

Název: CEITEC 2020 (Akronym: CEITEC2020)

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, CEITEC 2020

MUNI/A/1284/2015, interní kód MU

Název: Experimentální farmakologický vývoj v neuropsychiatrii a onkologii

Investor: Masarykova univerzita, Experimentální farmakologický vývoj v neuropsychiatrii a onkologii, DO R. 2020_Kategorie A - Specifický výzkum - Studentské výzkumné projekty

MUNI/11/InGA09/2014, interní kód MU

Název: Studium terapeuticky využitelných vlastností mikroRNA-215 v animálním modelu kolorektálního karcinomu (Akronym: miR-215 kolorektální karcinom)

Investor: Masarykova univerzita, Studium terapeuticky využitelných vlastností mikroRNA-215 v animálním modelu kolorektálního karcinomu

Citovat

VYCHYTILOVÁ, Petra; Jana MERHAUTOVÁ; Táňa MACHÁČKOVÁ; Irene GUTIERREZ-GARCIA; José GARCIA-SOLANO; Lenka RADOVÁ; Dominika BRCHNELOVÁ; Kateřina SLABÁ; Marek SVOBODA; Jana HALÁMKOVÁ; Regina DEMLOVÁ; Igor KISS; Rostislav VYZULA; Pablo CONESA-ZAMORA a Ondřej SLABÝ. MiR-215-5p is a tumor suppressor in colorectal cancer targeting EGFR ligand epiregulin and its transcriptional inducer HOXB9. Oncogenesis. New York, USA: Nature publishing group, 2017, roč. 6, č. 11, s. 399-412. ISSN 2157-9024. Dostupné z: https://doi.org/10.1038/s41389-017-0006-6.

@article{1405392,
   author = {Vychytilová, Petra and Merhautová, Jana and Macháčková, Táňa and GutierrezandGarcia, Irene and GarciaandSolano, José and Radová, Lenka and Brchnelová, Dominika and Slabá, Kateřina and Svoboda, Marek and Halámková, Jana and Demlová, Regina and Kiss, Igor and Vyzula, Rostislav and ConesaandZamora, Pablo and Slabý, Ondřej},
   article_location = {New York, USA},
   article_number = {11},
   doi = {https://doi.org/10.1038/s41389-017-0006-6},
   keywords = {miR-215; colorectal cancer; EGFR; proliferation; tumor suppressor; HOXB9; epiregulin},
   language = {eng},
   issn = {2157-9024},
   journal = {Oncogenesis},
   title = {MiR-215-5p is a tumor suppressor in colorectal cancer targeting EGFR ligand epiregulin and its transcriptional inducer HOXB9},
   url = {https://www.nature.com/articles/s41389-017-0006-6},
   volume = {6},
   year = {2017}
}

TY  - JOUR
ID  - 1405392
AU  - Vychytilová, Petra - Merhautová, Jana - Macháčková, Táňa - Gutierrez-Garcia, Irene - Garcia-Solano, José - Radová, Lenka - Brchnelová, Dominika - Slabá, Kateřina - Svoboda, Marek - Halámková, Jana - Demlová, Regina - Kiss, Igor - Vyzula, Rostislav - Conesa-Zamora, Pablo - Slabý, Ondřej
PY  - 2017
TI  - MiR-215-5p is a tumor suppressor in colorectal cancer targeting EGFR ligand epiregulin and its transcriptional inducer HOXB9
JF  - Oncogenesis
VL  - 6
IS  - 11
SP  - 399-412
EP  - 399-412
PB  - Nature publishing group
SN  - 21579024
KW  - miR-215
KW  - colorectal cancer
KW  - EGFR
KW  - proliferation
KW  - tumor suppressor
KW  - HOXB9
KW  - epiregulin
UR  - https://www.nature.com/articles/s41389-017-0006-6
L2  - https://www.nature.com/articles/s41389-017-0006-6
N2  - Growing evidence suggests that microRNAs are involved in the development and progression of colorectal cancer (CRC). In the present study, deregulation and functioning of tumor-suppressive miR-215-5p was evaluated in CRC. In total, 448 tumor tissues and 325 paired adjacent healthy tissues collected from Czech and Spain cohorts of CRC patients have been used for miR-215-5p expression analyses. A series of in vitro experiments have been performed using transient transfection of miR-215-5p mimics into four CRC cell lines to identify specific cellular processes affected by miR-215-5p. Further, the effects of miR-215-5p on tumor growth were evaluated in vivo using NSG mice and stable cell line overexpressing miR-215-5p. Target mRNAs of miR-215-5p were tested using luciferase assay and western blot analyses. We found that miR-215-5p is significantly downregulated in tumor tissues compared with non-tumor adjacent tissues and its decreased levels correlate with the presence of lymph node metastases, tumor stage, and shorter overall survival in CRC patients. Overexpression of miR-215-5p significantly reduced proliferation, clonogenicity, and migration of CRC cells, lead to cell cycle arrest in G2/M phase and p53-dependent induction of apoptosis. The ability of miR-215-5p to inhibit tumor growth was confirmed in vivo. Finally, we confirmed epiregulin and HOXB9 to be the direct targets of miR-215-5p. As epiregulin is EGFR ligand and HOXB9 is its transcriptional inducer, we suggest that the main molecular link between miR-215-5p and CRC cells phenotypes presents the EGFR signaling pathway, which is one of the canonical pathogenic pathways in CRC.
ER  -

VYCHYTILOVÁ, Petra; Jana MERHAUTOVÁ; Táňa MACHÁČKOVÁ; Irene GUTIERREZ-GARCIA; José GARCIA-SOLANO; Lenka RADOVÁ; Dominika BRCHNELOVÁ; Kateřina SLABÁ; Marek SVOBODA; Jana HALÁMKOVÁ; Regina DEMLOVÁ; Igor KISS; Rostislav VYZULA; Pablo CONESA-ZAMORA a Ondřej SLABÝ. MiR-215-5p is a tumor suppressor in colorectal cancer targeting EGFR ligand epiregulin and its transcriptional inducer HOXB9. \textit{Oncogenesis}. New York, USA: Nature publishing group, 2017, roč.~6, č.~11, s.~399-412. ISSN~2157-9024. Dostupné z: https://doi.org/10.1038/s41389-017-0006-6.

Přehled o publikaci