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

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Publikace nespadá pod Lékařskou fakultu, ale pod Středoevropský technologický institut. Oficiální stránka publikace je na webu muni.cz.

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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

Rok publikování 2017
Druh Článek v odborném periodiku
Časopis / Zdroj Oncogenesis
Fakulta / Pracoviště MU

Středoevropský technologický institut

Citace
www https://www.nature.com/articles/s41389-017-0006-6
Doi http://dx.doi.org/10.1038/s41389-017-0006-6
Obor Onkologie a hematologie
Klíčová slova miR-215; colorectal cancer; EGFR; proliferation; tumor suppressor; HOXB9; epiregulin
Popis 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.
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