Luan Na, Chen Yiquan, Li Qingsong, Mu Yali, Zhou Qin, Ye Xun, Deng Qun, Ling Limian, Wang Jian, Wang Jianwei
Department of Colorectal Surgery and Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine Jiefang Road 88th, Hangzhou 310016, China.
Department of Radiotherapy, The Second Affiliated Hospital of Zhejiang University School of Medicine Hangzhou 310009, China.
Am J Transl Res. 2021 Jan 15;13(1):124-142. eCollection 2021.
tRNA-derived fragments (tRFs) are derived from corresponding tRNAs and have been shown by several studies to be novel biological markers for tumour diagnosis and therapy. However, until now, the effects of tRFs on the progression of colorectal cancer (CRC) and especially on the epithelial-to-mesenchymal transition (EMT) have remained unknown. Our study aimed to assess CRC-related tRFs and examine the effects of key tRFs on CRC progression and related mechanisms. After hypoxic treatment, tRF sequencing and real-time PCR assays were performed to identify key tRFs. Then, functional tests were designed to verify the effects and evaluate the mechanism after cell transfection under normoxic conditions. A total of 14 tRFs were differentially expressed in the hypoxia and control groups. Based on the results of PCR assay verification and conditional selection, tRF-20-M0NK5Y93 could be a promising target for exploration, as its expression was significantly lower under hypoxic conditions than under control conditions. tRF-20-M0NK5Y93 inhibited CRC cell migration and invasion partly by targeting Claudin-1, an EMT-related molecule. The results of the present study suggest that tRF-20-M0NK5Y93 promotes CRC cell migration and invasion partly by regulating Claudin-1 during EMT.
转运RNA衍生片段(tRFs)来源于相应的转运RNA,多项研究表明其是肿瘤诊断和治疗的新型生物标志物。然而,迄今为止,tRFs对结直肠癌(CRC)进展的影响,尤其是对上皮-间质转化(EMT)的影响仍不清楚。我们的研究旨在评估与CRC相关的tRFs,并研究关键tRFs对CRC进展及相关机制的影响。经过缺氧处理后,进行tRF测序和实时PCR检测以鉴定关键tRFs。然后,设计功能测试以验证常氧条件下细胞转染后的作用并评估机制。缺氧组和对照组共有14种tRFs差异表达。基于PCR检测验证和条件筛选结果,tRF-20-M0NK5Y93有望成为探索的靶点,因为其在缺氧条件下的表达明显低于对照条件。tRF-20-M0NK5Y93通过靶向Claudin-1(一种与EMT相关的分子)部分抑制CRC细胞的迁移和侵袭。本研究结果表明,tRF-20-M0NK5Y93在EMT过程中通过调节Claudin-1部分促进CRC细胞的迁移和侵袭。