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Nuclear localization signal-enhanced RNA interference of EZH2 and Oct4 in the eradication of head and neck squamous Cell carcinoma-derived cancer stem cells

Paper ID Volume ID Publish Year Pages File Format Full-Text
6948 525 2012 17 PDF Available
Title
Nuclear localization signal-enhanced RNA interference of EZH2 and Oct4 in the eradication of head and neck squamous Cell carcinoma-derived cancer stem cells
Abstract

Metastasis is the major cause of high mortality in head and neck squamous cell carcinoma (HNSCC), in which HNSCC-derived cancer stem cells (CSCs) may be involved. Several reports have coupled non-viral gene delivery with RNA interference (RNAi) to target specific genes in cancer cells. However, the delivery efficiency of RNAi is limited and remained to be improved. Moreover, the therapeutic effect of non-viral gene delivery approaches on HNSCC-derived CSCs is still uncertain. In this study, we found that EZH2 and Oct4 are upregulated in HNSCC-derived ALDH1+/CD44+ CSC-like cells. Polyurethane-short branch PEI (PU-PEI)-based administration of double-stranded DNA (dsDNA) encoding small interfering RNA (siRNA) against EZH2 and Oct4 (siEZH2/siOct4) led to partial anti-cancer capacity and mild suppression of CSC-like properties. By pre-conjugation of nuclear localization signal (NLS) to siRNA-expressing dsDNA, the anti-cancer efficacy was enhanced due to elevated nuclear delivery. Notably, the NLS-preconjugated siEZH2/siOct4 constructs remarkably repressed epithelial-mesenchymal transdifferentiation (EMT) and radioresistance in ALDH1+/CD44+ CSC-like cells, in which Wnt5A and CyclinD1 may be involved respectively. We furthermore demonstrated that this improved method was capable of reducing tumor growth and metastasis in vivo. Our findings may provide a feasible non-viral gene delivery method to eradicate HNSCC-derived CSCs and improve HNSCC therapy.

Keywords
Small interfering RNA; Head and neck squamous cell carcinoma; EZH2; Oct4; Nuclear localization signal
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Nuclear localization signal-enhanced RNA interference of EZH2 and Oct4 in the eradication of head and neck squamous Cell carcinoma-derived cancer stem cells
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 33, Issue 14, May 2012, Pages 3693–3709
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us