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

Certain 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.