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Type: Artigo de periódico
Title: Low Mir-143/mir-145 Cluster Levels Induce Activin A Overexpression In Oral Squamous Cell Carcinomas, Which Contributes To Poor Prognosis
Author: Bufalino
Andreia; Cervigne
Nilva K.; de Oliveira
Carine Ervolino; Fonseca
Felipe Paiva; Rodrigues
Priscila Campioni; Soares Macedo
Carolina Carneiro; Sobral
Lays Martin; Miguel
Marcia Costa; Lopes
Marcio Ajudarte; Paes Leme
Adriana Franco; Lambert
Daniel W.; Salo
Tuula A.; Kowalski
Luiz Paulo; Graner
Edgard; Coletta
Ricardo D.
Abstract: 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.
Subject: Prostate-cancer Progression
Human Breast
Mesenchymal Transition
Citation: Low Mir-143/mir-145 Cluster Levels Induce Activin A Overexpression In Oral Squamous Cell Carcinomas, Which Contributes To Poor Prognosis. Public Library Science, v. 10, p. AUG-2015.
Rights: aberto
Identifier DOI: 10.1371/journal.pone.0136599
Date Issue: 2015
Appears in Collections:Unicamp - Artigos e Outros Documentos

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