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 in participating carcinogenesis of hepatocellular carcinoma, but its expression and potential role in TNBC progression is still unclear.
In the present study, Researchers from Peking University Health Science Center 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 knockdown 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 suggesting that they may be DANCR targets in TNBC. Thus, this study demonstrated that targeting DANCR expression might be a viable therapeutic approach to treat triple negative breast cancer.
DANCR repressed TNBC cancer stem cell markers expression
(A) Immunofluorescence assay was used to detect the protein level of CD44 and CD24 in MDA-MB-231 cells transfected with Scramble or siDANCR. (B) Shown is real time PCR assay data for the expression of CD44 gene in xenograft tissues generated from MDA-MD-231 cells infected with non-target control (shNC) or shDANCR (shDANCR). #, p<0.01. (C) Immunohistochemistry assay was used to detect the CD44 protein level in MDA-MB-231 cells infected with shNC or shDANCR. Representative images (200) were given in the graph. (D) Western blot assay and (E) real time PCR assay were used to detect the protein level and mRNA of ABCG2 and ALDH1 in MDAMB-231 cells transfected with Scramble or siDANCR, respectively. #, p<0.01.