RNA-Seq of NSCLC cells with overexpression of AS-tDR-008272

tRNA-derived fragments (tRFs) have been found to play regulatory roles in human cancers. However, the biogenesis, precise functions, and underlying mechanisms of tRFs in non-small-cell lung cancer (NSCLC) remain largely unexplored. Here, we identified a novel tRF, AS-tDR-008272, which was upregulated in NSCLC tumor tissues, plasma, and in NSCLC cells. Further analysis revealed that the biogenesis of AS-tDR-008272 was induced by angiogenin (ANG) under hypoxic conditions. Functional assays indicated that AS-tDR-008272 promoted the proliferation, migration, and glycolysis metabolism of NSCLC cells. While inhibition of AS-tDR-008272 suppressed NSCLC cell growth in vitro and in vivo. Clinically, higher expression of AS-tDR-008272 in NSCLC tumor tissues was associated with advanced TNM stage, poorer survival, and SUVmax of 18F-FDG PET/CT scan in NSCLC patients. Mechanistically, AS-tDR-008272 regulated NSCLC cell malignancy by interacting with HJURP in two ways: binding to the coding sequence (CDS) of HJURP mRNA to regulate its transcription and enhancing the abundance of HJURP mRNA in polysomes to promote its translation. Our findings reveal a previously unrecognized mechanism of tRF-mediated glycolysis reprogramming in NSCLC tumorigenesis. AS-tDR-008272 may represent a promising prognostic marker and therapeutic target for NSCLC.