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Molecular Cancer
Published in: Molecular Cancer 1/2014

Open Access 01-12-2014 | Research

Identification and characterization of Dicer1e, a Dicer1 protein variant, in oral cancer cells

Authors: Liliana P Cantini, Lourdes M Andino, Christopher C Attaway, Betsy Butler, Anca Dumitriu, Aaron Blackshaw, Andrew Jakymiw

Published in: Molecular Cancer | Issue 1/2014

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Abstract

Background

The human dicer1 gene has been predicted to produce several mRNA variants that encode truncated Dicer1 proteins of varying lengths. One of these Dicer1 variants, Dicer1e, was recently found to be differentially expressed in breast cancer cells. Because the expression and function of the Dicer1e protein variant has not been well characterized and the underlying molecular mechanisms for the development of oral squamous cell carcinomas (OSCCs) are poorly understood, the present study sought to characterize the biological role of Dicer1e and determine its relationship, if any, to OSCC pathogenesis.

Methods

Western blot analyses were used to examine Dicer1e expression levels in a panel of oral cancer cells/tissues and during epithelial-mesenchymal transition (EMT), followed by 5′/3′-RACE analyses to obtain the full-length Dicer1e transcript. Biochemical fractionation and indirect immunofluorescent studies were performed to determine the cellular localization of Dicer1e and the effects of Dicer1e silencing on cancer cell proliferation, clonogenicity, and drug sensitivity were also assessed.

Results

Dicer1e protein levels were found to be overexpressed in OSCC cell lines of epithelial phenotype and in OSCC tissues with its levels downregulated during EMT. Moreover, the Dicer1e protein was observed to predominantly localize in the nucleus. 5′/3′-RACE analyses confirmed the presence of the Dicer1e transcript and silencing of Dicer1e impaired both cancer cell proliferation and clonogenicity by inducing either apoptosis and/or G2/M cell cycle arrest. Lastly, Dicer1e knockdown enhanced the chemosensitivity of oral cancer cells to cisplatin.

Conclusion

The expression levels of Dicer1e influence the pathogenesis of oral cancer cells and alter their response to chemosensitivity, thus supporting the importance of Dicer1e as a therapeutic target for OSCCs.
Appendix
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Metadata
Title
Identification and characterization of Dicer1e, a Dicer1 protein variant, in oral cancer cells
Authors
Liliana P Cantini
Lourdes M Andino
Christopher C Attaway
Betsy Butler
Anca Dumitriu
Aaron Blackshaw
Andrew Jakymiw
Publication date
01-12-2014
Publisher
BioMed Central
Published in
Molecular Cancer / Issue 1/2014
Electronic ISSN: 1476-4598
DOI
https://doi.org/10.1186/1476-4598-13-190

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