Exploring Small Nucleolar RNA Host Gene 3 as a Therapeutic Target in Breast Cancer Through Metabolic Reprogramming

One of the main causes of death worldwide at the moment is cancer. Breast cancer (BC) is the most common type of cancer in women. Triple-negative breast cancer (TNBC) accounts for at least 14.6-20.6% of all incidences of BC. This study was conducted to provide evidence supporting the therapeutic use of combinatorial regimens of CDK4/6 inhibitors for TNBC patients. Exosomes were used to characterize cancer-associated fibroblasts (CAFs) from BC patients. The MD-MBA-453 and MCF7 cells were transfected using the labelled exosomes. Cell viability, extracellular acidification rate (ECAR), and OCR were determined. The expression levels of small nucleolar RNA host gene 3 (SNHG3), pyruvate kinase M1/M2 (PKM), and miR330-5p in the transfected cells were measured. Stable cell lines and a BC mouse model were generated to investigate test DNA and RNA sequences. The results showed that exosomes produced from CAFs were able to reprogram metabolic pathways following their absorption by tumor cells. PKM could be targeted by miR330-5p as well as SNHG3 in BC cells. By upregulating expression linked to miR330-5p and downregulating PKM in tumor cells, SNHG3 inhibited the growth of cells. Exosomes released by breast CAFs reduced the OCR of MD-MBA-453 and MCF-7 cells. Furthermore, it was observed that exosomes secreted by CAFs altered the metabolic pathways regarding BC cells and decreased mitochondrial activity. SNHG3 inhibited miR330 expression in vitro by acting like a molecular sponge. The findings of this study suggest that, when treating cancer, focusing on exosome-mediated communication between cancer and stromal cells may have therapeutic potential.