INFORMAZIONI SU
BUBUIANU Ionela Codruta
 |
Supervisore:Prof.ssa Antoniali Proteomic and miRnomic investigations of senescence-derived exosomes to identify circuits modulating cancer chemoresistance and tumour microenvironment |
| Emerging evidence highlights the pivotal role of extracellular vesicles (EVs) in driving tumour progression and promoting chemoresistance through intercellular signalling and induction of paracrine senescence. While the secretome of senescent cells has been extensively studied, the alterations in EV secretion by therapy-induced senescent (TIS) cells have only recently earned significant research attention. The cellular model intended to be used is chemotherapy-induced senescent lung cancer cells A549 wild type and A549-RelA knock-down which have NF-kB expression inhibited. This cell model allows us to explore the role of NF-kB in regulating the Senescence-Associated Secretory Phenotype (SASP) and exosome dynamics and composition. The research project aims to investigate the proteomic and miRNomic content of senescence-associated exosomes during the early (6 days) and late (10 days) stages of senescence. This distinction is critical, as the senescence-associated secretory phenotype (SASP) exhibits dual roles: acting as a tumour suppressor during the early phases of tumorigenesis while transitioning to an immunosuppressive function that promotes tumour progression in the later stages. Through a combination of molecular and screening strategies, we aim to identify proteins involved in DNA damage response (DDR) signalling, in microenvironment inflammation and the role of DDR/SASP-related miRNAs secreted in senescence-associated exosomes in modulating chemoresistance. The protein content of senescence-associated exosomes will be characterized by high-resolution nLC-MS/MS base methods, while the most differentially expressed miRNAs (DE-miRNAs) will be identified to elucidate their role in promoting chemoresistance in receiving cells. |
|