Low miR-143/miR-145 Cluster Levels Induce Activin A Overexpression in Oral Squamous Cell Carcinomas, Which Contributes to Poor Prognosis

Autor(es):Mostrar menos -

Bufalino, Andreia ^[1] ; Cervigne, Nilva K. ^[1] ; de Oliveira, Carine Ervolino ^[1] ; Fonseca, Felipe Paiva ^[1] ; Rodrigues, Priscila Campioni ^[1] ; Soares Macedo, Carolina Carneiro ^[1] ; Sobral, Lays Martin ^[1] ; Miguel, Marcia Costa ^{[2, 1]} ; Lopes, Marcio Ajudarte ^[1] ; Paes Leme, Adriana Franco ^[3] ; Lambert, Daniel W. ^{[4, 5]} ; Salo, Tuula A. ^{[6, 7, 8, 9, 1]} ; Kowalski, Luiz Paulo ^[10] ; Graner, Edgard ^[1] ; Coletta, Ricardo D. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Estadual Campinas, Sch Dent, Dept Oral Diag, Piracicaba, SP - Brazil

^[2] Univ Fed Rio Grande do Norte, Dept Dent, BR-59072970 Natal, RN - Brazil

^[3] CNPEM, Brazilian Biociences Natl Lab, Campinas, SP - Brazil

^[4] Univ Sheffield, Sch Clin Dent, Integrated Biosci, Sheffield, S Yorkshire - England

^[5] Univ Sheffield, Sheffield Canc Ctr, Sheffield, S Yorkshire - England

^[6] Univ Oulu, Oulu Univ Hosp, Oulu - Finland

^[7] Univ Oulu, Med Res Ctr, Oulu - Finland

^[8] Univ Helsinki, Inst Dent, Helsinki - Finland

^[9] Univ Oulu, Inst Dent, Dept Diagnost & Oral Med, Oulu - Finland

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

• Tipo de documento: Artigo Científico
• Fonte: PLoS One; v. 10, n. 8 AUG 28 2015.
• Citações Web of Science: 20

Resumo

Deregulated expression of activin A is reported in several tumors, but its biological functions in oral squamous cell carcinoma (OSCC) are unknown. Here, we investigate whether activin A can play a causal role in OSCCs. Activin A expression was assessed by qPCR and immunohistochemistry in OSCC tissues. Low activin A-expressing cells were treated with recombinant activin A and assessed for apoptosis, proliferation, adhesion, migration, invasion and epithelial-mesenchymal transition (EMT). Those phenotypes were also evaluated in high activin A-expressing cells treated with follistatin (an activin A antagonist) or stably expressing shRNA targeting activin A. Transfections of microRNA mimics were performed to determine whether the overexpression of activin A is regulated by miR-143/miR-145 cluster. Activin A was overexpressed in OSCCs in comparison with normal oral mucosa, and high activin A levels were significantly associated with lymph node metastasis, tumor differentiation and poor survival. High activin A levels promoted multiple properties associated with malignant transformation, including decreased apoptosis and increased proliferation, migration, invasion and EMT. Both miR-143 and miR-145 were markedly downregulated in OSCC cell lines and in clinical specimens, and inversely correlated to activin A levels. Forced expression of miR-143 and miR-145 in OSCC cells significantly decreased the expression of activin A. Overexpression of activin A in OSCCs, which is controlled by downregulation of miR-143/miR-145 cluster, regulates apoptosis, proliferation and invasiveness, and it is clinically correlated with lymph node metastasis and poor survival. (AU)

• Processo FAPESP: 13/01607-6 - Avaliação do papel biológico das proteínas EEF1D, fascina e plectina em carcinomas espinocelulares orais
• Beneficiário: Ricardo Della Coletta
• Modalidade de apoio: Auxílio à Pesquisa - Regular