Specific siRNA Targeting Receptor for Advanced Glycation End Products (RAGE) Decreases Proliferation in Human Breast Cancer Cell Lines

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.

Role of receptor for advanced glycation end products in the complication and progression of various types of cancers

“…In a similar study conducted by Radia et al, it was discovered that on treating breast cancer cell lines of MCF-7, SK-Br-3 and MDA-MB-231 with RAGE siRNA, the tumor cells failed to progress beyond G1 phase of cell cycle [35]. Another study conducted by Lata K et al involving the treatment of MCF-7 breast cancer cells with 17α-EE enhances the expression of estrogen receptor related receptor gamma (ERRγ, a member of nuclear hormone receptor superfamily) followed by enhanced level of oxidative stress and subsequent activation of the transcription factor, nuclear factor kappa-B (NF-кB) (Fig.…”

RAGE Mediates S100A7-Induced Breast Cancer Growth and Metastasis by Modulating the Tumor Microenvironment

“…We documented that RAGE is highly expressed in human TNBC and murine breast cancer cell lines and weakly expressed in low metastatic ER+ cells. However, there are some conflicting reports regarding the expression of RAGE in the MCF7 cell line (40-41). It could be due to the difference in the techniques which were employed.…”

“…Using a genetic approach, we showed that RAGE ablation significantly reduced PyMT cell-derived tumor growth while blocking RAGE with neutralizing antibodies inhibits breast cancer visceral metastasis in preclinical mouse models. It has been shown recently that RAGE knockdown by siRNA significantly inhibited tumorigenic potential of MDA-MB231 cell line (40). RAGE ablation in a triple transgenic model of spontaneous pancreatic cancer has also been shown to delay pancreatic cancer development (9,43).…”

Increased Expression of the Receptor for Advanced Glycation End-Products (RAGE) Is Associated with Advanced Breast Cancer Stage

“…Another study showed that the targeting of RAGE by specific small interfering RNAs (siRNAs) in different breast cancer cell lines decreased the proliferation of all subtypes of breast cancer [37]. …”