{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nCircTLCD4‐RWDD3 is a newly discovered circular RNA that is markedly upregulated in extracellular vesicles secreted by lymph node metastatic non‐small cell lung cancer (NSCLC) cells. High levels of EV-packaged circTLCD4-RWDD3 correlate with poorer overall and disease-free survival in patients. Importantly, downregulation of circTLCD4-RWDD3 in vitro and in vivo has been shown to inhibit lymphangiogenesis and subsequent lymph node metastasis, highlighting its contribution to the progression of NSCLC."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}, {"type": "p", "children": [{"type": "t", "text": "\nMechanistic studies revealed that circTLCD4-RWDD3 physically interacts with the RNA-binding protein hnRNPA2B1 and facilitates its SUMO2 modification at the K108 residue via upregulation of UBC9. This SUMOylated hnRNPA2B1 is then recognized by the SUMO interaction motif of ALIX, leading to its activation and subsequent recruitment of ESCRT-III proteins that mediate the efficient sorting of circTLCD4-RWDD3 into NSCLC-derived EVs. Once released and internalized by lymphatic endothelial cells, circTLCD4-RWDD3 activates the transcription of PROX1, thereby triggering lymphangiogenesis and promoting lymph node metastasis. These findings not only elucidate the functional role of circTLCD4-RWDD3 in NSCLC progression but also underscore its potential as a therapeutic target to prevent metastasis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}]}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Xiayao Diao, Chao Guo, Hanhao Zheng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SUMOylation-triggered ALIX activation modulates extracellular vesicles circTLCD4-RWDD3 to promote lymphatic metastasis of non-small cell lung cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Signal Transduct Target Ther (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41392-023-01685-0"}], "href": "https://doi.org/10.1038/s41392-023-01685-0"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37925421"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37925421"}]}]}]}