mRNA-Targeting Antisense Oligonucleotide Blocks Cell Proliferation and Induces Apoptosis in Breast Cancer Cell Lines.

The luminal B molecular subtype of breast cancers (BC) accounts for more than a third of BCs and is associated with aggressive clinical behavior and poor prognosis. The use of endocrine therapy in BC treatment has significantly contributed to the decrease in the number of deaths in recent years. However, most BC patients with prolonged exposure to estrogen receptor (ER) selective modulators such as tamoxifen develop resistance and become non-responsive over time. Recent studies have implicated overexpression of the gene in BC resistance to endocrine drugs, thereby highlighting inhibition as an attractive modality in BC treatment, especially luminal B BCs. However, there is no known inhibitor of due to its nuclear association and non-enzymatic activity. Here, we have developed an antisense oligonucleotide (ASO) against mRNA and shown that it downregulates protein expression. inhibition decreased cell proliferation and induced apoptosis. Combined with cisplatin, the anti-cancer effects of -ASO9 were improved. Moreover, our work shows that ASO technology may be used to increase the number of targetable cancer genes.