miR-22 and miR-205 Drive Tumor Aggressiveness of Mucoepidermoid Carcinomas of Salivary Glands
Kuasne Hellen; Leivo Ilmo; Al-Samadi Ahmed; Kowalski Luiz Paulo; Silvia Vanessa; Naakka Erika; Marchi Fabio Albuquerque; Passador-Santos Fabricio; Rogatto Silvia Regina; Suleymanova Ilida; Barros-Filho Mateus Camargo; Brown Amy Louise; Araujo Vera Cavalcanti; Mäkitie Antti; Salo Tuula; Scapulatempo-Neto Cristovam Lourenco; Castilho Rogerio Morae; Korelin Katja; Adnan-Awad Shady
miR-22 and miR-205 Drive Tumor Aggressiveness of Mucoepidermoid Carcinomas of Salivary Glands
Kuasne Hellen
Leivo Ilmo
Al-Samadi Ahmed
Kowalski Luiz Paulo
Silvia Vanessa
Naakka Erika
Marchi Fabio Albuquerque
Passador-Santos Fabricio
Rogatto Silvia Regina
Suleymanova Ilida
Barros-Filho Mateus Camargo
Brown Amy Louise
Araujo Vera Cavalcanti
Mäkitie Antti
Salo Tuula
Scapulatempo-Neto Cristovam Lourenco
Castilho Rogerio Morae
Korelin Katja
Adnan-Awad Shady
FRONTIERS MEDIA SA
Julkaisun pysyvä osoite on:
https://urn.fi/URN:NBN:fi-fe2022081154059
https://urn.fi/URN:NBN:fi-fe2022081154059
Tiivistelmä
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.
Kokoelmat
- Rinnakkaistallenteet [19207]