Targeting Cell Cycle Proteins in Breast Cancer Cells with siRNA by Using Lipid-Substituted Polyethylenimines

Frontiers in Bioengineering and Biotechnology
Manoj B ParmarHasan Uludag

Abstract

The cell cycle proteins are key regulators of cell cycle progression whose deregulation is one of the causes of breast cancer. RNA interference (RNAi) is an endogenous mechanism to regulate gene expression and it could serve as the basis of regulating aberrant proteins including cell cycle proteins. Since the delivery of small interfering RNA (siRNA) is a main barrier for implementation of RNAi therapy, we explored the potential of a non-viral delivery system, 2.0 kDa polyethylenimines substituted with linoleic acid and caprylic acid, for this purpose. Using a library of siRNAs against cell cycle proteins, we identified cell division cycle protein 20 (CDC20), a recombinase RAD51, and serine-threonine protein kinase CHEK1 as effective targets for breast cancer therapy, and demonstrated their therapeutic potential in breast cancer MDA-MB-435, MDA-MB-231, and MCF7 cells with respect to another well-studied cell cycle protein, kinesin spindle protein. We also explored the efficacy of dicer-substrate siRNA (DsiRNA) against CDC20, RAD51, and CHEK1, where a particular DsiRNA against CDC20 showed an exceptionally high inhibition of cell growth in vitro. There was no apparent effect of silencing selected cell cycle proteins on the poten...Continue Reading

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Citations

Sep 30, 2017·International Journal of Cancer. Journal International Du Cancer·Bindu ThapaHasan Uludağ
Feb 6, 2017·Macromolecular Bioscience·Daniel Nisakar Meenakshi SundaramHasan Uludağ
Jul 2, 2021·International Journal of Pharmaceutics·Rahul ChadarPrashant Kesharwani

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Methods Mentioned

BETA
transfection
flow cytometry
PCR
xenograft
confocal microscopy
flow
Assay
xenografts

Software Mentioned

ZEN
Imaris
QuantaSoft

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