tRNA衍生的小RNA（tsRNA）是新发现的非编码RNA，由tRNA产生，据报道参与疾病，特别是癌症的多种生物过程；然而，tsRNA参与结直肠癌（CRC）和5-氟尿嘧啶（5-FU）的机制仍不清楚。通过RNA测序来鉴定CRC组织中tsRNA的差异表达。 CCK8、集落形成、transwell 测定和肿瘤球测定用于研究 tsRNA-GlyGCC 在 CRC 5-FU 耐药中的作用。 TargetScan和miRanda用于鉴定tsRNA-GlyGCC的靶基因。使用生物素 Pull-down、RNA Pull-down、荧光素酶测定、ChIP 和蛋白质印迹来探索 tsRNA-GlyGCC 作用的潜在分子机制。 MeRIP 检测用于研究 tsRNA-GlyGCC 的 N(7)-甲基鸟苷 RNA 修饰。在这项研究中，我们揭示了人类结直肠癌组织中 tsRNA 的特征，并确认了一个特定的 5' half tRNA，5'tiRNA-Gly- GCC (tsRNA-GlyGCC)，在 CRC 组织中上调，并通过 METTL1 介导的 N(7)-甲基鸟苷 tRNA 修饰进行调节。体外和体内实验揭示了 tsRNA-GlyGCC 在 CRC 5-FU 耐药性中的致癌作用。值得注意的是，我们的结果表明 tsRNA-GlyGCC 通过靶向 SPIB 调节 JAK1/STAT6 信号通路。合成聚(β-氨基酯)来辅助递送5-FU和tsRNA-GlyGCC抑制剂，有效抑制肿瘤生长并增强CRC对5-FU的敏感性，且对皮下肿瘤没有明显的副作用。我们的研究揭示了一种特定的tsRNA -CRC进展中GlyGCC参与途径。靶向 tsRNA-GlyGCC 与 5-FU 组合可能为治疗 5-FU 耐药性 CRC 提供一种有前途的纳米治疗策略。© 2024。作者。

tRNA-derived small RNAs (tsRNAs) are newly discovered non-coding RNA, which are generated from tRNAs and are reported to participate in several biological processes in diseases, especially cancer; however, the mechanism of tsRNA involvement in colorectal cancer (CRC) and 5-fluorouracil (5-FU) is still unclear.RNA sequencing was performed to identify differential expression of tsRNAs in CRC tissues. CCK8, colony formation, transwell assays, and tumor sphere assays were used to investigate the role of tsRNA-GlyGCC in 5-FU resistance in CRC. TargetScan and miRanda were used to identify the target genes of tsRNA-GlyGCC. Biotin pull-down, RNA pull-down, luciferase assay, ChIP, and western blotting were used to explore the underlying molecular mechanisms of action of tsRNA-GlyGCC. The MeRIP assay was used to investigate the N(7)-methylguanosine RNA modification of tsRNA-GlyGCC.In this study, we uncovered the feature of tsRNAs in human CRC tissues and confirmed a specific 5' half tRNA, 5'tiRNA-Gly-GCC (tsRNA-GlyGCC), which is upregulated in CRC tissues and modulated by METTL1-mediated N(7)-methylguanosine tRNA modification. In vitro and in vivo experiments revealed the oncogenic role of tsRNA-GlyGCC in 5-FU drug resistance in CRC. Remarkably, our results showed that tsRNA-GlyGCC modulated the JAK1/STAT6 signaling pathway by targeting SPIB. Poly (β-amino esters) were synthesized to assist the delivery of 5-FU and tsRNA-GlyGCC inhibitor, which effectively inhibited tumor growth and enhanced CRC sensitive to 5-FU without obvious adverse effects in subcutaneous tumor.Our study revealed a specific tsRNA-GlyGCC-engaged pathway in CRC progression. Targeting tsRNA-GlyGCC in combination with 5-FU may provide a promising nanotherapeutic strategy for the treatment of 5-FU-resistance CRC.© 2024. The Author(s).