Programmed cell death 4 loss increases tumor cell invasion and is regulated by miR-21 in oral squamous cell carcinoma

Molecular Cancer

Research

Melania Pintilie¹  Igor Jurisica²  Patrick J Gullane³  Ralph W Gilbert³  Jonathan C Irish³  Reidar Grénman⁴  Bayardo Perez-Ordonez⁵  Mahadeo A Sukhai⁶  Nilva K Cervigne⁷  Patricia P Reis⁷  Jerry Machado⁸  Miranda Tomenson⁹  Suzanne Kamel-Reid^1,10 

[1] Dalla Lana School of Public Health Sciences, University of Toronto, Toronto, Ontario, Canada;Department of Biostatistics, Princess Margaret Hospital, University Health Network, Toronto, Ontario, Canada;Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada;Department of Computer Science, University of Toronto, Toronto, Ontario, Canada;Ontario Cancer Institute and the Campbell Family Institute for Cancer Research, University Health Network, Toronto, Ontario, Canada;Department of Otolaryngology/Surgical Oncology, Princess Margaret Hospital, Ontario Cancer Institute and The University Health Network, Toronto, Ontario, Canada;Department of Otorhinolaryngology/Head and Neck Surgery, Turku University Central Hospital, Turku, Finland;Department of Biochemistry, Turku University Central Hospital, Turku, Finland;Department of Pathology, Toronto General Hospital, Ontario Cancer Institute, University Health Network, Toronto, Ontario, Canada;Division Of Cancer Genomics and Proteomics, Ontario Cancer Institute, University Health Network, Toronto, Ontario, Canada;Division of Applied Molecular Oncology, Princess Margaret Hospital, Ontario Cancer Institute, University Health Network, Toronto, Ontario, Canada;Division of Applied Molecular Oncology, Princess Margaret Hospital, Ontario Cancer Institute, University Health Network, Toronto, Ontario, Canada;Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada;Division of Applied Molecular Oncology, Princess Margaret Hospital, Ontario Cancer Institute, University Health Network, Toronto, Ontario, Canada;Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada;Division of Applied Molecular Oncology, Princess Margaret Hospital, Ontario Cancer Institute, University Health Network, Toronto, Ontario, Canada;Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada;Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada;Department of Pathology, Toronto General Hospital, Ontario Cancer Institute, University Health Network, Toronto, Ontario, Canada;

关键词: Oral Squamous Cell Carcinoma;    Oral Squamous Cell Carcinoma;    Oral Squamous Cell Carcinoma Patient;    Oral Squamous Cell Carcinoma Cell Line;    PDCD4 Expression;   

DOI  :  10.1186/1476-4598-9-238

 received in 2010-05-05, accepted in 2010-09-10,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundThe tumor suppressor Programmed Cell Death 4 (PDCD4) has been found to be under-expressed in several cancers and associated with disease progression and metastasis. There are no current studies characterizing PDCD4 expression and its clinical relevance in Oral Squamous Cell Carcinoma (OSCC). Since nodal metastasis is a major prognostic factor in OSCC, we focused on determining whether PDCD4 under-expression was associated with patient nodal status and had functional relevance in OSCC invasion. We also examined PDCD4 regulation by microRNA 21 (miR-21) in OSCC.ResultsPDCD4 mRNA expression levels were assessed in 50 OSCCs and 25 normal oral tissues. PDCD4 was under-expressed in 43/50 (86%) OSCCs, with significantly reduced mRNA levels in patients with nodal metastasis (p = 0.0027), and marginally associated with T3-T4 tumor stage (p = 0.054). PDCD4 protein expression was assessed, by immunohistochemistry (IHC), in 28/50 OSCCs and adjacent normal tissues; PDCD4 protein was absent/under-expressed in 25/28 (89%) OSCCs, and marginally associated with nodal metastasis (p = 0.059). A matrigel invasion assay showed that PDCD4 expression suppressed invasion, and siRNA-mediated PDCD4 loss was associated with increased invasive potential of oral carcinoma cells. Furthermore, we showed that miR-21 levels were increased in PDCD4-negative tumors, and that PDCD4 expression may be down-regulated in OSCC by direct binding of miR-21 to the 3'UTR PDCD4 mRNA.ConclusionsOur data show an association between the loss of PDCD4 expression, tumorigenesis and invasion in OSCC, and also identify a mechanism of PDCD4 down-regulation by microRNA-21 in oral carcinoma. PDCD4 association with nodal metastasis and invasion suggests that PDCD4 may be a clinically relevant biomarker with prognostic value in OSCC.

【 授权许可】

Unknown   
© Reis et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.