Refereed journal article or data article (A1)

miR-22 and miR-205 Drive Tumor Aggressiveness of Mucoepidermoid Carcinomas of Salivary Glands




List of AuthorsNaakka Erika, Barros-Filho Mateus Camargo, Adnan-Awad Shady, Al-Samadi Ahmed, Marchi Fabio Albuquerque, Kuasne Hellen, Korelin Katja, Suleymanova Ilida, Brown Amy Louise, Scapulatempo-Neto Cristovam Lourenco, Silvia Vanessa, Castilho Rogerio Morae, Kowalski Luiz Paulo, Mäkitie Antti, Araujo Vera Cavalcanti, Leivo Ilmo, Rogatto Silvia Regina, Salo Tuula, Passador-Santos Fabricio

PublisherFRONTIERS MEDIA SA

PlaceBasel

Publication year2022

JournalFrontiers in Oncology

Journal name in sourceFRONTIERS IN ONCOLOGY

Journal acronymFRONT ONCOL

Article number 786150

Volume number11

Number of pages13

ISSN2234-943X

DOIhttp://dx.doi.org/10.3389/fonc.2021.786150

URL https://doi.org/10.3389/fonc.2021.786150

Self-archived copy’s web addresshttps://research.utu.fi/converis/portal/detail/Publication/174891845


Abstract
ObjectivesTo integrate mRNA and miRNA expression profiles of mucoepidermoid carcinomas (MECs) and normal salivary gland (NSGs) tissue samples and identify potential drivers. Material and MethodsGene and miRNA expression arrays were performed in 35 MECs and six NSGs. ResultsWe found 46 differentially expressed (DE) miRNAs and 3,162 DE mRNAs. Supervised hierarchical clustering analysis of the DE transcripts revealed two clusters in both miRNA and mRNA profiles, which distinguished MEC from NSG samples. The integrative miRNA-mRNA analysis revealed a network comprising 696 negatively correlated interactions (44 miRNAs and 444 mRNAs) involving cell signaling, cell cycle, and cancer-related pathways. Increased expression levels of miR-205-5p and miR-224-5p and decreased expression levels of miR-139-3p, miR-145-3p, miR-148a-3p, miR-186-5p, miR-338-3p, miR-363-3p, and miR-4324 were significantly related to worse overall survival in MEC patients. Two overexpressed miRNAs in MEC (miR-22 and miR-205) were selected for inhibition by the CRISPR-Cas9 method. Cell viability, migration, and invasion assays were performed using an intermediate grade MEC cell line. Knockout of miR-205 reduced cell viability and enhanced ZEB2 expression, while miR-22 knockout reduced cell migration and invasion and enhanced ESR1 expression. Our results indicate a distinct transcriptomic profile of MEC compared to NSG, and the integrative analysis highlighted miRNA-mRNA interactions involving cancer-related pathways, including PTEN and PI3K/AKT. ConclusionThe in vitro functional studies revealed that miR-22 and miR-205 deficiencies reduced the viability, migration, and invasion of the MEC cells suggesting they are potential oncogenic drivers in MEC.

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Last updated on 2022-19-05 at 16:49