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

Investor logo

Warning

This publication doesn't include Faculty of Arts. It includes Central European Institute of Technology. Official publication website can be found on muni.cz.
Authors

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

Year of publication 2017
Type Article in Periodical
Magazine / Source Oncogenesis
MU Faculty or unit

Central European Institute of Technology

Citation
Web https://www.nature.com/articles/s41389-017-0006-6
Doi http://dx.doi.org/10.1038/s41389-017-0006-6
Field Oncology and hematology
Keywords miR-215; colorectal cancer; EGFR; proliferation; tumor suppressor; HOXB9; epiregulin
Description 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.
Related projects:

You are running an old browser version. We recommend updating your browser to its latest version.