Role of N6-Methyladenosine (m6A) mRNA Modification Pathway in Neuroblastoma
Neuroblastoma is the most common type of cancer in infants, and the fourth most common type of all cancers diagnosed in children. It's a disease of high mortality rate with more than 50% diagnosed patients belong to the high-risk group. The high-risk neuroblastoma is highly aggressive, commonly disseminating to bone marrow, bone, liver, skin and other organs, resulting in bad outcomes in patients. Despite the recent research and therapeutic advances, the survival rate for children with high-risk neuroblastoma remains disappointingly low. Therefore the identification of novel oncogenic pathways and new therapeutic targets in neuroblastoma is an urgent unmet need in this aggressive cancer.
Our lab has recently identified a novel oncogenic m6A mRNA modification pathway that is essential for growth, survival, and invasion of lung cancers. Interestingly, our preliminary analysis uncovered that the m6A modification enzymes are misregulated in neuroblastoma. Importantly, the higher expression of m6A enzymes (METTL3, METTL14) significantly correlates with poorer neuroblastoma patient survival, while higher expression of m6A demethylases (remove m6A modification) FTO and ALKBH5 significantly correlates with better patient survival. These data suggest critical functions of m6A modification pathway in regulation of neuroblastoma.
The goal of this proposal is to profile neuroblastoma specific m6A modifications and investigate the molecular functions and physiological relevance of m6A modification pathway in neuroblastoma. Completion of this proposed study will uncover novel neuroblastoma molecular markers and therapeutic targets and will facilitate the long-term objectives to develop new diagnostic markers and cancer therapeutic drugs for the treatment of neuroblastoma