tsRNAs sequencing reveals tRNA-Gly (GCC)-derived small RNAs as colorectal cancer biomarker

Colorectal cancer (CRC) is one of the most common gastrointestinal tumors and the second leading cause of malignancy-related death worldwide. Novel biomarkers with high sensitivity and specificity are necessary to improve the diagnosis of colorectal cancer (CRC) in terms of early diagnosis and prognosis. In this study, we obtained tsRNAs expression profiles from formalin-fixed and paraffin-embedded (FFPE) clinical tissue samples to identify novel tsRNAs with potential biomarker properties in colorectal cancer. The expression profiles of colorectal cancer tsRNAs were successfully constructed, 612 up-regulated and 439 down-regulated tsRNAs were identified in the tumor group. tRNA-Gly (GCC)-derived i-tRF-Gly-GCC and 5′-tRF-Gly-GCC were highly expressed in CRC tissues compared to the paraneoplastic tissues. The same results were found in serum from colorectal cancer patients compared to serum from healthy volunteers. Both tsRNAs were highly expressed in CRC tissues and the AUC in ROC analysis was greater than 0.7, which has clinical diagnostic value. WGCNA analysis showed that the target genes of the two tsRNAs were closely related to CRC, and the expression of the target genes was significantly decreased in the cancer groups of the COAD and READ datasets. We also performed validation experiments in HCT-116 cells, and the results confirmed that i-tRF-Gly-GCC and 5′-tRF-Gly-GCC significantly enhanced cell proliferation and migration. In conclusion, we identified and characterized two tsRNAs (i-tRF-Gly-GCC and 5′-tRF-Gly-GCC) as the biomarkers for the diagnosis of colorectal cancer.