Specific siRNA targeting receptor for advanced glycation end products (RAGE) decreases proliferation in human breast cancer cell lines

Al-Madhagi Radia; Al-Madhagi Yaser; Xiaoqian Ma; Juan Zhang; Cejun Yang; Qiong Dong; Pengfei Rong; Bin Ye; Sheng Liu; Wei Wang

doi:10.3390/ijms14047959

Specific siRNA targeting receptor for advanced glycation end products (RAGE) decreases proliferation in human breast cancer cell lines

Int J Mol Sci. 2013 Apr 11;14(4):7959-78. doi: 10.3390/ijms14047959.

Authors

Al-Madhagi Radia¹, Al-Madhagi Yaser, Xiaoqian Ma, Juan Zhang, Cejun Yang, Qiong Dong, Pengfei Rong, Bin Ye, Sheng Liu, Wei Wang

Affiliation

¹ Cell Transplantation and Gene Therapy Institute, Department of Radiology, the Third Xiang Ya Hospital of Central South University, Changsha 410013, China. wawe01cn@yahoo.com.cn.

Abstract

Receptor for Advanced Glycation End Products (RAGE) is an oncogenic trans-membranous receptor overexpressed in various human cancers. However, the role of RAGE in breast cancer development and proliferation is still unclear. In this study, we demonstrated that RAGE expression levels are correlated to the degree of severity of breast cancer. Furthermore, there is a decrease in the proliferation of all sub-types of breast cancer, MCF-7, SK-Br-3 and MDA-MB-231, as a result of the effect of RAGE siRNA. RAGE siRNA arrested cells in the G1 phase and inhibited DNA synthesis (p < 0.05). Moreover, qRT-PCR and Western Blot results demonstrated that RAGE siRNA decreases the expression of transcriptional factor NF-κB p65 as well as the expression of cell proliferation markers PCNA and cyclinD1. RAGE and RAGE ligands can thus be considered as possible targets for breast cancer management and therapy.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Apoptosis
Breast Neoplasms / genetics*
Breast Neoplasms / metabolism
Breast Neoplasms / pathology*
Cell Line, Tumor
Cell Proliferation
Cell Survival
Cyclin D1 / genetics
DNA, Neoplasm / biosynthesis
Female
G1 Phase Cell Cycle Checkpoints
Gene Expression
Gene Knockdown Techniques
Humans
MCF-7 Cells
Proliferating Cell Nuclear Antigen / genetics
RNA, Messenger / genetics
RNA, Messenger / metabolism
RNA, Neoplasm / genetics
RNA, Neoplasm / metabolism
RNA, Small Interfering / genetics*
RNA, Small Interfering / therapeutic use
Receptor for Advanced Glycation End Products
Receptors, Immunologic / antagonists & inhibitors*
Receptors, Immunologic / genetics*
Receptors, Immunologic / metabolism
Transcription Factor RelA / genetics
Triple Negative Breast Neoplasms / genetics
Triple Negative Breast Neoplasms / metabolism
Triple Negative Breast Neoplasms / pathology

Substances

CCND1 protein, human
DNA, Neoplasm
Proliferating Cell Nuclear Antigen
RELA protein, human
RNA, Messenger
RNA, Neoplasm
RNA, Small Interfering
Receptor for Advanced Glycation End Products
Receptors, Immunologic
Transcription Factor RelA
Cyclin D1