Analysis of cellular and exosomal RNAs in AC16 cells regulated by hypertrophic cardiomyocyte [MDA-MB-231]

Cardiovascular diseases (CVDs) and cancer are among the most serious life-threatening diseases with very high morbidity and mortality rates. An increasing number of clinical studies have shown that cardiovascular disease is strongly associated with an increased risk of cancer and can contribute to cancer development, but the mechanisms associated with this need to be further explored in depth. Exosomes play an important role in promoting the development of cancer, and breast cancer is the most prevalent cancer among women. In the present study, we showed by in vivo experiments that exosomes from hypertrophic cardiomyocytes significantly promote breast cancer progression. In order to explore the mechanism by which hypertrophic cardiomyocytes promote the progression of breast cancer, we conducted whole transcriptome sequencing of exosomes and cells from normal cardiomyocytes and hypertrophic cardiomyocytes. Interestingly, the majority of miRNAs were downregulated in the exosomes of hypertrophic cardiomyocytes. In the downregulated miRNAs within the exosomes of hypertrophic cardiomyocytes, a consistent sequence GGCXGAGG was identified. We found that hnRNPQ regulates exosomal sorting of miR-10400-3p and several other miRNAs. Based on this, we validated the expression levels of plasma exosomal miRNAs in patients with myocardial hypertrophy using clinical data and patient samples, providing predictive markers for cancer progression in myocardial hypertrophy patients. Our findings suggest that hypertrophic cardiomyocytes regulate the expression of the RNA-binding protein hnRNPQ, which affects the levels of exosomal miRNAs and plays a key role in promoting the development of breast cancer.