Hypoxia-induced tRF-3

Hypoxia is one of the major characteristics of the tumor microenvironment, and it promotes mitochondrial energy metabolic remodeling for hepatocellular carcinoma (HCC) progression. It is believed that under dual control of the mitochondrial genome (mtDNA) and the nuclear genome (nDNA) mitochondria coordinate multiple signals to alter energy metabolism under hypoxic stress. Currently, it has been found that hypoxia promotes tRNA cleavage to produce tRFs (tRNA-derived fragment), which have attracted attention as potential biomarkers and therapeutic targets. In this study, we found that hypoxic stress could drive HCC cell invasion and migration. Furthermore, the expression of core oxidative phosphorylation (OXPHOS) proteins encoded by nDNA and mtDNA were uncoordinated under hypoxia. Therefore, the human mitochondrial peptide deformylase (HsPDF) which was essential for mtDNA-encoded protein translation and respiratory chain maintenance has been brought into focus. We found that hypoxic stress significantly suppressed HsPDF which was responsible for mtDNA-encoded protein inhibition. To further explore the possible mechanism, high-throughput sequencing was used to map tRF expression patterns in HCC cells under hypoxia. We found that hypoxic stress altered their subtype distributions and that the high expression of tRF-3