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

Author(s):Show less -

Naakka, Erika ^{[1, 2]} ; Barros-Filho, Mateus Camargo ^[3] ; Adnan-Awad, Shady ^{[2, 4]} ; Al-Samadi, Ahmed ^{[1, 2]} ; Marchi, Fabio Albuquerque ^[3] ; Kuasne, Hellen ^[3] ; Korelin, Katja ^{[1, 2]} ; Suleymanova, Ilida ^{[1, 2]} ; Brown, Amy Louise ^[5] ; Scapulatempo-Neto, Cristovam ^[6] ; Lourenco, Silvia Vanessa ^{[7, 8]} ; Castilho, Rogerio Moraes ^[9] ; Kowalski, Luiz Paulo ^{[10, 11]} ; Maekitie, Antti ^{[12, 13, 14, 15, 16]} ; Araujo, Vera Cavalcanti ^[5] ; Leivo, Ilmo ^{[17, 18]} ; Rogatto, Silvia Regina ^{[19, 20]} ; Salo, Tuula ^{[21, 1, 22, 2, 23]} ; Passador-Santos, Fabricio ^[5]

Affiliation:Show less -

^[1] Univ Helsinki, Dept Oral & Maxillofacial Dis, Helsinki - Finland

^[2] Univ Helsinki, Translat Immunol Res Program TRIMM, Helsinki - Finland

^[3] AC Camargo Canc Ctr, Ctr Int Pesquisa CIPE, Sao Paulo - Brazil

^[4] Univ Helsinki, Hematol Res Unit, Dept Clin Chem & Hematol, Helsinki Univ Hosp, Comprehens Canc Ctr, Helsinki - Finland

^[5] Fac Sao Leopoldo Mandic, Dept Oral Pathol, Campinas - Brazil

^[6] Mol Oncol Res Ctr Barretos & Diagnost Amer DASA, Barueri - Brazil

^[7] AC Camargo Canc Ctr, Dept Pathol, Sao Paulo - Brazil

^[8] Univ Sao Paulo, Dent Sch, Dept Gen Pathol, Sao Paulo - Brazil

^[9] Univ Michigan, Sch Dent, Dept Periodont & Oral Med, Ann Arbor, MI 48109 - USA

^[10] AC Camargo Canc Ctr, Dept Head & Neck Surg & Otorhinolaryngol, Sao Paulo - Brazil

^[11] Univ Sao Paulo, Dept Head & Neck Surg, Sch Med, Sao Paulo - Brazil

^[12] Helsinki Univ Hosp, Helsinki - Finland

^[13] Univ Helsinki, Dept Otorhinolaryngol Head & Neck Surg, Helsinki - Finland

^[14] Univ Helsinki, Res Program Syst Oncol, Fac Med, Helsinki - Finland

^[15] Karolinska Inst, Div Ear Nose & Throat Dis, Dept Clin Sci Intervent & Technol, Stockholm - Sweden

^[16] Karolinska Hosp, Stockholm - Sweden

^[17] Turku Univ Hosp, Turku - Finland

^[18] Univ Turku, Inst Biomed, Pathol, Turku - Finland

^[19] Univ Southern Denmark, Inst Reg Hlth Res, Odense - Denmark

^[20] Univ Hosp Southern Denmark, Dept Clin Genet, Vejle - Denmark

^[21] Oulu Univ Hosp, Med Res Ctr, Oulu - Finland

^[22] Univ Oulu, Canc & Translat Med Res Unit, Oulu - Finland

^[23] Helsinki Univ Hosp, Dept Pathol, Helsinki - Finland

• Document type: Journal article
• Source: FRONTIERS IN ONCOLOGY; v. 11, FEB 9 2022.
• Web of Science Citations: 0

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. (AU)

• FAPESP's process: 12/10382-5 - MicroRNA and gene expression integrated study on mucoepidermoid carcinomas of salivary glands
• Grantee: Fabricio Passador-Santos
• Support Opportunities: Regular Research Grants
• FAPESP's process: 13/04045-9 - Integrated study of gene expression and microRNA in mucoepidermoid carcinoma of the salivary glands
• Grantee: Amy Louise Brown
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)