5'-tRF-GlyGCC：一种新型的 tRNA 衍生的小 RNA 作为结直肠癌诊断的新型生物标志物。
5'-tRF-GlyGCC: a tRNA-derived small RNA as a novel biomarker for colorectal cancer diagnosis.
机构信息
Guangdong Key Laboratory of Chiral Molecule and Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, Guangdong, China.
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.
出版信息
Genome Med. 2021 Feb 9;13(1):20. doi: 10.1186/s13073-021-00833-x.
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.
背景
tRNA 衍生的小 RNA（tDRs）广泛分布于人体组织中，包括血液和尿液，在癌症的进展中发挥重要作用。然而，CRC 血浆中 tDRs 的表达及其潜在的诊断价值尚未得到系统研究。
方法
通过小 RNA 测序研究 CRC 患者和健康对照者（HCs）血浆中 tDRs 的表达谱。通过定量 PCR 检测 105 例 CRC 患者和 90 例 HCs 血浆样本中 5'-tRF-GlyGCC 的水平和诊断价值。通过体外和体内模型检查 5'-tRF-GlyGCC 生物发生的机制。
结果
与 HCs 相比，CRC 患者血浆中的 5'-tRF-GlyGCC 明显增加。5'-tRF-GlyGCC 在 CRC 组的 AUC 为 0.882。CEA 和 CA199 与 5'-tRF-GlyGCC 的联合可将 AUC 提高至 0.926。同样，CRC 细胞及其相应对照物中的 5'-tRF-GlyGCC 表达水平显著更高。与 CRC 细胞共培养的血细胞或移植有 CRC 肿瘤的小鼠显示出 5'-tRF-GlyGCC 水平增加。此外，我们发现 5'-tRF-GlyGCC 的表达增加依赖于 tRNA 去甲基酶 AlkB 同源物 3（ALKBH3）的上调，ALKBH3 可促进 tRNA 切割以产生 tDRs。
结论
血浆中 5'-tRF-GlyGCC 的水平是 CRC 诊断的有前途的诊断生物标志物。
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