Multiple suppressing small interfering RNA for cancer treatment—Application to triple‐negative breast cancer

Abstract

AbstractCertain cancers, such as triple‐negative breast cancer (TNBC), pose a challenging prognosis due to the absence of identifiable hormone‐related receptors and effective targeted therapies. Consequently, novel therapeutics are required for these cancers, offering minimal side effects and reduced drug resistance. Unexpectedly, siRNA‐7, initially employed as a control, exhibited significant efficacy in inhibiting cell viability in MDA‐MB‐231 cells. Through a genome‐wide search of seed sequences, the targets of siRNA‐7 were identified as cancer‐related genes, namely PRKCE, RBPJ, ZNF737, and CDC7 in MDA‐MB‐231 cells. The mRNA repression analysis confirmed the simultaneous suppression by siRNA‐7. Combinatorial administration of single‐targeting siRNAs demonstrated a comparable reduction in viability to that achieved by siRNA‐7. Importantly, siRNA‐7 selectively inhibited cell viability in MDA‐MB‐231 cells, while normal HDF‐n cells remained unaffected. Furthermore, in a xenograft mouse model, siRNA‐7 exhibited a remarkable 76% reduction in tumor volume without any loss in body weight. These findings position siRNA‐7 as a promising candidate for a novel, safe, specific, and potent TNBC cancer therapeutic. Moreover, the strategy of multiple suppressing small interfering RNA holds potential for the treatment of various diseases associated with gene overexpression.