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

Show full item record



Permalink

http://hdl.handle.net/10138/160529

Citation

Bufalino , A , Cervigne , N K , de Oliveira , C E , Fonseca , F P , Rodrigues , P C , Soares Macedo , C C , Sobral , L M , Miguel , M C , Lopes , M A , Paes Leme , A F , Lambert , D W , Salo , T A , Kowalski , L P , Graner , E & Coletta , R D 2015 , ' Low miR-143/miR-145 Cluster Levels Induce Activin A Overexpression in Oral Squamous Cell Carcinomas, Which Contributes to Poor Prognosis ' PLoS One , vol. 10 , no. 8 , 0136599 . DOI: 10.1371/journal.pone.0136599

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.
Contributor: University of Helsinki, Department of Oral and Maxillofacial Diseases
Date: 2015-08-28
Language: eng
Number of pages: 22
Belongs to series: PLoS One
ISSN: 1932-6203
URI: http://hdl.handle.net/10138/160529
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
TGF-BETA
MESENCHYMAL TRANSITION
PROLIFERATION
EXPRESSION
GROWTH
METASTASIS
APOPTOSIS
INVASION
313 Dentistry
3111 Biomedicine
Rights:


Files in this item

Total number of downloads: Loading...

Files Size Format View
journal.pone.0136599.PDF 4.255Mb PDF View/Open

This item appears in the following Collection(s)

Show full item record