Raman spectroscopy reveals a novel mechanism by which cyclin Y promotes breast cancer progression by regulating lipid metabolism.

Raman spectroscopy is a technique for disease diagnosis and treatment evaluation through directly measuring the molecular features of cellular metabolites at the single-cell level. Nevertheless, the application of Raman spectroscopy in studying the mechanisms of breast cancer remains limited. Cyclins are critical regulators of cell proliferative activity that are often dysregulated in cancer. Although cyclin Y (CCNY), as a key cyclin, is increasingly recognized as an oncogene in various cancers, including lung, renal, hepatocellular, ovarian and laryngeal cancers, CCNY, which is essential for the progression of breast cancer, remains elusive. Here, we investigate the function of CCNY in breast cancer progression, focusing on the regulation of nucleic acid levels and lipid metabolism activity. We find that deletion of CCNY dramatically inhibits DNA synthesis and spindle formation coupled with reduced proliferation and arrested cell cycle of breast cancer cells in vitro. Loss of CCNY significantly suppresses breast cancer progression and metastasis in murine and patient-derived xenograft models. Mechanistically, single-cell Raman spectroscopy and RNA-seq reveal that CCNY mediates the progression of breast cancer by regulating key cell cycle regulators, nucleic acid production and metabolic reprogramming. Moreover, high CCNY expression is associated with poor prognosis in breast cancer. Our findings uncover a critical role of CCNY in regulating tumor progression of breast cancer through regulating nucleic acid levels and lipid metabolism activity, which suggests that exploring CCNY-targeted therapies could be a potential future direction for breast cancer treatment.