Targeting long non-coding RNA DANCR inhibits triple negative breast cancer progression

Abstract

Triple negative breast cancer (TNBC) is non-responsive to conventional anti-hormonal and Her2-targeted therapies, making it necessary to identify new molecular targets for therapy. Long non-coding RNA anti-differentiation ncRNA (lncRNA DANCR) was identified participating in carcinogenesis of hepatocellular carcinoma, but its expression and potential role in TNBC progression is still unclear. In the present study, our results showed that DANCR expression was increased in TNBC tissues compared with the adjacent normal tissues using quantitative real-time PCR (qRT-PCR) in 63 TNBC specimens. Patients with higher DANCR expression correlated with worse TNM stages as well as a shorter overall survival (OS) using Kaplan–Meier analysis. When the endogenous DANCR was knocked-down via specific siRNA, cell proliferation and invasion were decreased obviously in the MDA-MB-231 cells. In vivo xenograft experiments showed that knockdown of the DANCR in MDA-MB-231 cells reduced the tumor growth significantly. Furthermore, a compendium of TNBC cancer stem cell markers such as CD44, ABCG2 transporter and aldehyde dehydrogenase (ALDH1) were greatly downregulated in the MDA-MB-231 cells with DANCR knockdown. Molecular mechanistic studies revealed that knockdown of DANCR was associated with increased binding of EZH2 on the promoters of CD44 and ABCG2, and concomitant reduction of expression of these genes suggested that they may be DANCR targets in TNBC. Thus, our study demonstrated that targeting DANCR expression might be a viable therapeutic approach to treat triple negative breast cancer.

Keywords

• Triple negative breast cancers (TNBC)
• Long non-coding RNA
• DANCR
• Cancer stem cell