Dr. Yujie Ma - Best of the Best in Pediatric Surgery 2025

All right. So, um, we're going to go on to the next heat. Um, and uh, so now we're going to be having uh, Paps and Caps, uh, going head to head here. Um, so the first presentation, uh, is Dr. Yuli Ma, uh, and it's Cam K2G promotes neuronal differentiation and inhibits migration in neuroblastoma. And uh, Yuli comes from Children's Hospital of Fudan University in China. Thank you for very kind introduction. I'd like to take this opportunity to present our work of CAMK2G promotes neuronal differentiation and inhibits migration in neuroblastoma. Neuroblastoma is the most common extracranial solid tumor of childhood arising from abert differentiation of sympatho adreno cells in neural crest. Retinoid acid is used to induce differentiation in treatment of high risk neuroblastoma. However, its efficacy varied in patients due to the highly heterogeneity of this disease. Therefore, identifying a novel differentiation mechanism is of great importance to develop effective therapy. Our previous publication in Cancer Cell has identified PCP4 as one of the differentiation markers of neuroblastoma tumor cells. So, in this study, we aim to explore the underlying mechanism in order to find better treatment options for patients. Functionally, PCP4 modulate the rate of calcium binding to calmodulin, which is a critical step in activating calmodulin dependent kinase. Here, we verified in neuroblastoma the binding of PCP4 with calmodulin by co-immunoprecipitation and using mass spectrometry, we identified a target kindness of calmodulin, CAMK2G. CAMK2G is a member of the Serine 30in protein kinase family. It plays an important role in neuronal development and synaptic plasticity, which is similar to that of PCP4. But its function in neuroblastoma has been largely uncharacterized. When it is activated by calmodulin, it gets autophosphorylated at the site of 30in 287. Here, we show that PCP4 overexpression upregulated the 30in 287 phosphor relation of CAMK2G in neuroblastoma cells. These results lead us to hypothesize that PCP4 may affect neuroblastoma differentiation by activating CAMK2G. So next, we investigate the clinical relevance of CAMK2G expression with the help of our two platform. We found that low CAMK2G MRNA expression was associated with worst overall and event free survival. advance ISS stages and unfavorable histology as well as MC amplifies status, high risk and tumor progression. These results indicated the tumor suppressive role of CAMK2G in neuroblastoma tumor Genesis. To explore the function of CAMK2G in neuroblastoma, we knocked down CAMK2G in SKNSH cells and we observed inhibited neuro right outgrowth even under the induction of retinoic acid. And the expression of neuronal differentiation markers were also downregulated following CAMK2G knockdown. These changes were further verified transcriptionally by RNA sequencing. GO enrichment analysis conducted in the downregulated genes show that enriched terms were related to neuronal differentiation, such as synaptic signaling, plasma membrane and iron channel activity. Ye down of CAMK2G also promote migration and invasion of neuroblastoma cells as shown by trans well essays. And KEGG analysis in upregulated genes identified enriched pathways, mainly associated with tumor migration and invasion, such as extracellular matrix receptor interaction, focal adhesion and regulation of acting cyto skeleton. So, in conclusion, in this study, we found CAMK2G expression is associated with favorable clinical features. We highlighted the essential role of CAMK2G in promoting neuronal differentiation and inhibiting migration in neuroblastoma. Future studies are needed to look for uncle proteins, which are upregulated, activated or blocked from degradation in CAMK2G low expressed neuroblastoma tumors, so that we can put up with novel therapeutic strategies. Thank you for your attention. I'd like to take any questions. Perfect. Thank you so much for the paper and, um, thanks for joining us. Uh, and I don't know, what time is it there right now? It's in the evening, 10 o'clock. Thank you. Um, so, um, Mira, do you want to introduce Dr. Brown? Yeah, so we're excited to have Dr. Aaron Brown join us. She's an associate professor of surgery at UC Davis and does both clinical and, uh, research focused on neuroblastoma. Hi everybody. How are you? Great presentation, Dr. Ma. Thank you. Um, my question for you is how universal is this downregulation of CAM CAMK2G across neuroblastoma cells? As you mentioned, it's really heterogene genius. And so that's a problem when developing these targeted therapies. So how, how are you seeing this across different neuroblastoma cell lines? Oh, well, we test the expression of CAMK2G in multiple neuroblastoma cell lines and uh, it's really it's expressed low in SKNSH cells. That's why we overexpress PCP4. Sorry, over express CAMK2G in this cell line and in other cell lines such as BE2, SKNS, it's it is highly expressed. Uh, but the in this cell lines were MYCN amplified cell lines and uh, during the study we found the CAMK2G, its function is not that strong to uh, overcome the gene function of make N. Uh, CAMK2G uh, didn't regulate the neuronal differentiation in this cell lines. So, um, so I think uh, this sorry. That's okay. to go finish. Sorry, it's hard to speak English. Um, uh, so uh, I think uh, this mechanism is not universal for all the neuroblastoma cellular and patients. Uh, it can only be explained in make a non-amplified cell lines and the corresponding patients. Thank you. Thank you so much. Very well presented. Thank you. Beautiful paper, beautiful presentation. I see why they chose your paper. So, thanks for the presentation. Just stick around and, um, if there's any questions, uh, we'll send them to you.