Yuan Xiwei, Li Wei, Li Jingjing, Zhang Wujun, Xiong Yue, Tang Han, Lan Baozhen, Huang Jinye, Chen Ye, Liu Wei, Zhou Chuanyi
Department of OncologyII, Yueyang People's Hospital, Yueyang Hospital affiliated to Hunan Normal University, Yueyang 414014, China.
Pathology Department, Yueyang People's Hospital, Yueyang Hospital affiliated to Hunan Normal University, Yueyang 414014, China.
Cell Signal. 2025 Aug;132:111813. doi: 10.1016/j.cellsig.2025.111813. Epub 2025 Apr 21.
Tumor incidence, progression, and metastasis may be linked to the aberrant levels of novel non-coding RNA tRNA-derived fragments (tRFs). Uncertainty surrounds the role and possible mechanism of tRF-3019 A in causing colon cancer to proceed malignantly.
By using qRT-PCR, transcription levels of tRF-3019 A were found in colon cancer cell lines and clinical samples. Locked nucleic acid (LNA)-tRF-3019 A or small molecule mimic was utilized to control the levels of tRF-3019 A in cells, and the CCK8 test was employed to assess the cells' capacity for proliferation. The rate of cell migration and invasiveness were assessed using the Transwell Assay. GFP-LC3B formation was seen using fluorescence microscopy, and autophagy-related protein expression was found using western blot analysis. The interactions between STAU1 and BECN1 and between tRF-3019 A and STAU1 were confirmed by RNA pull-down assay and RNA immunoprecipitation analyses. The mRNA and protein expression of STAU1 and BECN1 were found using qRT-PCR and western blot (WB). A xenograft tumor model was constructed to observe the growth of mouse tumors. qRT-PCR was used to detect the transcription levels of tRF-3019 A, STAU1, and BECN1, while WB was used to detect the expression of STAU1, BECN1, autophagy-related proteins, and epithelial-mesenchymal transition (EMT) -related proteins in tumor tissues.
In colon cancer tissues and cells, tRF-3019 A was overexpressed, and by triggering autophagy, it may encourage cell division, migration, and invasion. From a mechanistic perspective, tRF-3019 A competitively bound to the STAU1 protein with BECN1 mRNA, thereby enhancing the stable expression of the autophagy-related protein BECN1. In the model of xenograft tumor mice with knockdown of STAU1, blocking tRF-3019 A led to a substantial decrease in the pace of tumor development, a reduction in the expression of EMT-related proteins and autophagy, and an inhibition of autophagy.
tRF-3019A activated tumor cell autophagy and promoted the malignant progression of colon cancer by competitively binding to the STAU1 protein with BECN1 mRNA.
肿瘤的发生、发展和转移可能与新型非编码RNA tRNA衍生片段（tRFs）的异常水平有关。tRF-3019 A在结肠癌恶性进展中的作用及可能机制尚不清楚。
采用qRT-PCR检测结肠癌细胞系和临床样本中tRF-3019 A的转录水平。利用锁核酸（LNA）-tRF-3019 A或小分子模拟物控制细胞中tRF-3019 A的水平，并采用CCK8试验评估细胞的增殖能力。使用Transwell试验评估细胞迁移率和侵袭性。通过荧光显微镜观察GFP-LC3B的形成，并使用蛋白质印迹分析检测自噬相关蛋白的表达。通过RNA下拉试验和RNA免疫沉淀分析证实了STAU1与BECN1之间以及tRF-3019 A与STAU1之间的相互作用。使用qRT-PCR和蛋白质印迹（WB）检测STAU1和BECN1的mRNA和蛋白表达。构建异种移植肿瘤模型以观察小鼠肿瘤的生长。使用qRT-PCR检测tRF-3019 A、STAU1和BECN1的转录水平，同时使用WB检测肿瘤组织中STAU1、BECN1、自噬相关蛋白和上皮-间质转化（EMT）相关蛋白的表达。
在结肠癌组织和细胞中，tRF-3019 A过表达，并且通过触发自噬，它可能促进细胞分裂、迁移和侵袭。从机制角度来看，tRF-3019 A与BECN1 mRNA竞争性结合STAU1蛋白，从而增强自噬相关蛋白BECN1的稳定表达。在敲低STAU1的异种移植肿瘤小鼠模型中，阻断tRF-3019 A导致肿瘤发展速度大幅降低，EMT相关蛋白表达和自噬减少，并抑制自噬。
tRF-3019A通过与BECN1 mRNA竞争性结合STAU1蛋白激活肿瘤细胞自噬并促进结肠癌的恶性进展。
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