This study investigates the role of tiRNA-Val-CAC-2 in pancreatic cancer metastasis. The authors identified tiRNA-Val-CAC-2 as a highly expressed tsRNA in pancreatic cancer metastasis samples and serum from patients with metastatic disease. Overexpression of tiRNA-Val-CAC-2 promoted metastasis, while its knockdown inhibited it. Mechanistically, tiRNA-Val-CAC-2 interacts with FUBP1, enhancing FUBP1 protein stability and enrichment in the c-MYC promoter region, thereby increasing c-MYC transcription. Rescue experiments confirmed that tiRNA-Val-CAC-2 influences pancreatic cancer metastasis via FUBP1-mediated c-MYC transcription. These findings highlight tiRNA-Val-CAC-2 and FUBP1 as potential prognostic biomarkers and therapeutic targets for pancreatic cancer.This study investigates the role of tiRNA-Val-CAC-2 in pancreatic cancer metastasis. The authors identified tiRNA-Val-CAC-2 as a highly expressed tsRNA in pancreatic cancer metastasis samples and serum from patients with metastatic disease. Overexpression of tiRNA-Val-CAC-2 promoted metastasis, while its knockdown inhibited it. Mechanistically, tiRNA-Val-CAC-2 interacts with FUBP1, enhancing FUBP1 protein stability and enrichment in the c-MYC promoter region, thereby increasing c-MYC transcription. Rescue experiments confirmed that tiRNA-Val-CAC-2 influences pancreatic cancer metastasis via FUBP1-mediated c-MYC transcription. These findings highlight tiRNA-Val-CAC-2 and FUBP1 as potential prognostic biomarkers and therapeutic targets for pancreatic cancer.