Yingmin Wu1, Xiangling Yang2,3, Guanmin Jiang4, Haisheng Zhang1, Lichen Ge5, Feng Chen1, Jiexin Li6, Huanliang Liu7,8, Hongsheng Wang9. 1. Guangdong Key Laboratory of Chiral Molecule and Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, Guangdong, China. 2. Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510655, Guangdong, China. 3. Department of Clinical Laboratory, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510655, Guangdong, China. 4. Department of Clinical Laboratory, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, 519000, Guangdong, China. 5. Department of Clinical Laboratory, Jinling Hospital, Medical School of Nanjing University, Nanjing, 210002, China. 6. Guangdong Key Laboratory of Chiral Molecule and Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, Guangdong, China. lijiexin3@mail.sysu.edu.cn. 7. Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510655, Guangdong, China. liuhuanl@mail.sysu.edu.cn. 8. Department of Clinical Laboratory, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510655, Guangdong, China. liuhuanl@mail.sysu.edu.cn. 9. Guangdong Key Laboratory of Chiral Molecule and Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, Guangdong, China. whongsh@mail.sysu.edu.cn.
Abstract
BACKGROUND: tRNA-derived small RNAs (tDRs), which are widely distributed in human tissues including blood and urine, play an important role in the progression of cancer. However, the expression of tDRs in colorectal cancer (CRC) plasma and their potential diagnostic values have not been systematically explored. METHODS: The expression profiles of tDRs in plasma of CRC and health controls (HCs) are investigated by small RNA sequencing. The level and diagnostic value of 5'-tRF-GlyGCC are evaluated by quantitative PCR in plasma samples from 105 CRC patients and 90 HCs. The mechanisms responsible for biogenesis of 5'-tRF-GlyGCC are checked by in vitro and in vivo models. RESULTS: 5'-tRF-GlyGCC is dramatically increased in plasma of CRC patients compared to that of HCs. The area under curve (AUC) for 5'-tRF-GlyGCC in CRC group is 0.882. The combination of carcinoembryonic antigen (CEA) and carbohydrate antigen 199 (CA199) with 5'-tRF-GlyGCC improves the AUC to 0.926. Consistently, the expression levels of 5'-tRF-GlyGCC in CRC cells and xenograft tissues are significantly greater than that in their corresponding controls. Blood cells co-cultured with CRC cells or mice xenografted with CRC tumors show increased levels of 5'-tRF-GlyGCC. In addition, we find that the increased expression of 5'-tRF-GlyGCC is dependent on the upregulation of AlkB homolog 3 (ALKBH3), a tRNA demethylase which can promote tRNA cleaving to generate tDRs. CONCLUSIONS: The level of 5'-tRF-GlyGCC in plasma is a promising diagnostic biomarker for CRC diagnosis.
BACKGROUND: tRNA-derived small RNAs (tDRs), which are widely distributed in human tissues including blood and urine, play an important role in the progression of cancer. However, the expression of tDRs in colorectal cancer (CRC) plasma and their potential diagnostic values have not been systematically explored. METHODS: The expression profiles of tDRs in plasma of CRC and health controls (HCs) are investigated by small RNA sequencing. The level and diagnostic value of 5'-tRF-GlyGCC are evaluated by quantitative PCR in plasma samples from 105 CRC patients and 90 HCs. The mechanisms responsible for biogenesis of 5'-tRF-GlyGCC are checked by in vitro and in vivo models. RESULTS: 5'-tRF-GlyGCC is dramatically increased in plasma of CRC patients compared to that of HCs. The area under curve (AUC) for 5'-tRF-GlyGCC in CRC group is 0.882. The combination of carcinoembryonic antigen (CEA) and carbohydrate antigen 199 (CA199) with 5'-tRF-GlyGCC improves the AUC to 0.926. Consistently, the expression levels of 5'-tRF-GlyGCC in CRC cells and xenograft tissues are significantly greater than that in their corresponding controls. Blood cells co-cultured with CRC cells or mice xenografted with CRC tumors show increased levels of 5'-tRF-GlyGCC. In addition, we find that the increased expression of 5'-tRF-GlyGCC is dependent on the upregulation of AlkB homolog 3 (ALKBH3), a tRNA demethylase which can promote tRNA cleaving to generate tDRs. CONCLUSIONS: The level of 5'-tRF-GlyGCC in plasma is a promising diagnostic biomarker for CRC diagnosis.
Entities:
Keywords:
5′-tRF-GlyGCC; ALKBH3; CRC; Plasma; tRNA-derived small RNAs
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