The Role of Extracellular Vesicle-Mediated snoRNA Transfer in Breast Cancer Progression

Breast cancer (BC) is one of the most common types of cancer in women, and in order to effectively treat and control it, a better understanding of its molecular mechanisms is essential. Extracellular vesicles (EVs) are small particles enclosed with phospholipid bilayer that can contain RNA, DNA, proteins, lipids and other molecules, and serve as a crucial mechanism for intercellular communication. In previous studies, we have demonstrated that EVs derived from breast and prostate cancer patients contain snoRNAs and snoRNA-derived small RNAs (sdRNAs), while in plasma EVs from healthy controls the level of these molecules was much lower. Additionally, the levels of 23 snoRNAs decreased after surgery, suggesting they originated from tumor-associated cells, and 13 snoRNAs were linked to poor responses to neoadjuvant chemotherapy. The goal of this project is to explore the functions of selected snoRNAs/sdRNAs in BC development and progression. This will be achieved by investigating the significance of these snoRNAs in breast cancer cell lines through snoRNA knockdown or overexpression, and the effects will be analyzed by long-read and direct RNA sequencing. Furthermore, we will assess the transfer of EV-encapsulated snoRNAs to the tumor microenvironment and their impact on the cells within this environment. Gaining such insights could open new possibilities for targeted drug therapies and provide potential biomarkers to aid in both early tumor diagnosis and prognosis.