alexa Identification of Critical Biomarkers Responsive to Ant
ISSN: 1948-593X

Journal of Bioanalysis & Biomedicine
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Research Article

Identification of Critical Biomarkers Responsive to Anti-Autophagy Therapies for Pancreatic Ductal Adenocarcinoma through a Performance Analysis of miRNA Platforms

Sylvia H Sardi1*#, Brian J Glassner2#, J Robert Chang1, Sun Hee Yim3
1Laboratory for Innovative and Translational Technologies, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA
2WaferGen Biosystems Inc., 7400 Paseo Padre Parkway, Fremont, CA 94555, USA
3Division of Genetics, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA
#These authors contributed equally to the manuscript
Corresponding Author : Sylvia H Sardi
Harvard Catalyst-Laboratory for Innovative and Translational Technologies
Harvard Medical School, 77 Avenue Louis Pasteur
Boston, Massachusetts 02115, USA
Tel: 617-244-2964
E-mail: [email protected]
Received September 18, 2014; AcceptedOctober 30, 2014; Published November 01, 2014
Citation: Sardi SH, Glassner BJ, Chang JR, Yim SH (2014) Identification of Critical Biomarkers Responsive to Anti-Autophagy Therapies for Pancreatic Ductal Adenocarcinoma through a Performance Analysis of miRNA Platforms. J Bioanal Biomed S10:001. doi:10.4172/1948-593X.S10-001
Copyright: © 2014 Sardi SH, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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Abstract

Background: Autophagy is a fundamental catabolic pathway that involves the degradation of unnecessary or dysfunctional cellular components through the lysosomal machinery. The role of autophagy in cancer is complex, exhibiting tumor suppressive or tumor proliferative effects depending on the cancer type. Pancreatic ductal adenocarcinoma has constitutively activated autophagy that results in the selective proliferation of its tumor cells. Understanding the mechanisms by which the inhibition of autophagy occurs could shape our current therapeutic strategies for pancreatic cancer. Recent research has implicated microRNAs as important regulators of autophagy, but how miRNAs influence this inhibition is largely unexplored. Results: It is known that there exists inter-platform variability across miRNA platforms and therefore in order to identify bona fide miRNAs that are involved with the inhibition of autophagy we carried out a performance analysis of miRNA arrays from three vendors. In this paper we report our findings from this cross-platform analysis of miRNA arrays and the identity of several critical biomarkers of response to anti-autophagy therapies in the immortalized human pancreatic ductal adenocarcinoma cells 8988T as compared to normal human pancreatic ductal epithelial cells. Our cross-platform analysis of three different miRNA arrays revealed that RT-PCR-based technologies provide higher inter-platform reproducibility than hybridization-based technologies, a greater sensitivity indicated by larger dynamic ranges and reduced processing time. We also discovered two miRNAs, miRNA 720 and miRNA 29b to play a role in the inhibition of autophagy in 8988T cells and found miRNA 30a to be involved with the inhibition of autophagy in normal human pancreatic ductal epithelial cells. Conclusion: This cross-platform analysis of miRNA arrays contributed significant information about miRNA expression systems and led to the first report of miRNAs implicated in the inhibition of autophagy in pancreatic ductal adenocarcinoma. Our findings should provide new insights for developing therapeutic solutions for this extremely intractable disease.

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