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MiR-7-5p inhibits thyroid cell proliferation by targeting the EGFR/MAPK and IRS2/PI3K signaling pathways

2021; Impact Journals LLC; Volume: 12; Issue: 16 Linguagem: Inglês

10.18632/oncotarget.28030

1949-2553

Alice Augenlicht, Manuel Saiselet, Myriam Decaussin‐Petrucci, Guy Andry, Jacques E. Dumont, Carine Maenhaut,

Cancer-related molecular mechanisms research

// Alice Augenlicht 1 , Manuel Saiselet 1 , Myriam Decaussin-Petrucci 2 , Guy Andry 3 , Jacques E. Dumont 1 and Carine Maenhaut 1 1 Institute of Interdisciplinary Research, Université libre de Bruxelles, Brussels, Belgium 2 Service d'Anatomie et Cytologie Pathologiques, Centre Hospitalier Lyon Sud, Université Lyon 1, Pierre Benite Cedex 69495, France 3 Surgery Department, J. Bordet Institute, Brussels 1000, Belgium Correspondence to: Carine Maenhaut, email: carine.maenhaut@ulb.be Keywords: miRNA; papillary thyroid carcinoma; IRS2; MAPK; PI3K Received: December 15, 2020 Accepted: July 13, 2021 Published: August 03, 2021 Copyright: © 2021 Augenlicht et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. ABSTRACT The aberrant expression of miRNAs is often correlated to tumor development. MiR-7-5p is a recently discovered downregulated miRNA in thyroid papillary carcinoma (PTC). The goal of this project was to characterize its functional role in thyroid tumorigenesis and to identify the targeted modulated pathways. MiR-7-5p overexpression following transfection in TPC1 and HT-ori3 cells decreased proliferation of the two thyroid cell lines. Analysis of global transcriptome modifications showed that miR-7-5p inhibits thyroid cell proliferation by modulating the MAPK and PI3K signaling pathways which are both necessary for normal thyroid proliferation and play central roles in PTC tumorigenesis. Several effectors of these pathways are indeed targets of miR-7-5p, among which EGFR and IRS2, two upstream activators. We confirmed the upregulation of IRS2 and EGFR in human PTC and showed the existence of a negative correlation between the decreased expression of miR-7-5p and the increased expression of IRS2 or EGFR. Our results thus support a tumor-suppressor activity of miR-7-5p. The decreased expression of miR-7-5p during PTC tumorigenesis might give the cells a proliferative advantage and delivery of miR-7-5p may represent an innovative approach for therapy.