Xu Weiguo, Zhou Bin, Wang Juan, Tang Li, Hu Qing, Wang Jian, Chen Huanhuan, Zheng Junyu, Yan Feng, Chen Huanqiu
Department of General Surgery, Jiangsu Cancer Hospital & The Affiliated Cancer Hospital of Nanjing Medical University & Jiangsu Institute of Cancer Research, Nanjing, China.
Department of Oncology, Jiangsu Cancer Hospital & The Affiliated Cancer Hospital of Nanjing Medical University & Jiangsu Institute of Cancer Research, Nanjing, China.
Front Oncol. 2021 Aug 23;11:733763. doi: 10.3389/fonc.2021.733763. eCollection 2021.
Transfer RNA-derived RNA fragments (tRFs) belong to non-coding RNAs (ncRNAs) discovered in most carcinomas. Although some articles have demonstrated the characteristics of tRFs in gastric carcinoma (GC), the underlying mechanisms still need to be elucidated. Meanwhile, it was reported that the MAPK pathway was momentous in GC progression. Thus we focused on investigating whether tRF-Glu-TTC-027 could act as a key role in the progression of GC with the regulation of the MAPK pathway. We collected the data of the tRNA-derived fragments expression profile from six paired clinical GC tissues and corresponding adjacent normal samples in this study. Then we screened tRF-Glu-TTC-027 for analysis by using RT-PCR. We transfected GC cell lines with tRF-Glu-TTC-027 mimics or mimics control. Then the proliferation, migration, and invasion assays were performed to assess the influence of tRF-Glu-TTC-027 on GC cell lines. Fluorescence hybridization assay was conducted to confirm the cell distribution of tRF-Glu-TTC-027. We confirmed the mechanism that tRF-Glu-TTC-027 influenced the MAPK signaling pathway and observed a strong downregulation of tRF-Glu-TTC-027 in clinical GC samples. Overexpression of tRF-Glu-TTC-027 suppressed the malignant activities of GC and . MAPK signaling pathway was confirmed to be a target pathway of tRF-Glu-TTC-027 in GC by western blot. This is the first study to show that tRF-Glu-TTC-027 was a new tumor-suppressor and could be a potential object for molecular targeted therapy in GC.
转移RNA衍生的RNA片段(tRFs)属于在大多数癌症中发现的非编码RNA(ncRNAs)。尽管一些文章已经阐述了tRFs在胃癌(GC)中的特征,但其潜在机制仍有待阐明。同时,有报道称丝裂原活化蛋白激酶(MAPK)通路在GC进展中至关重要。因此,我们聚焦于研究tRF-Glu-TTC-027是否通过调控MAPK通路在GC进展中发挥关键作用。在本研究中,我们收集了6对临床GC组织及其相应癌旁正常样本的tRNA衍生片段表达谱数据。然后我们通过逆转录聚合酶链反应(RT-PCR)筛选tRF-Glu-TTC-027进行分析。我们用tRF-Glu-TTC-027模拟物或模拟物对照转染GC细胞系。然后进行增殖、迁移和侵袭实验,以评估tRF-Glu-TTC-027对GC细胞系的影响。进行荧光杂交实验以确认tRF-Glu-TTC-027的细胞分布。我们证实了tRF-Glu-TTC-027影响MAPK信号通路的机制,并观察到临床GC样本中tRF-Glu-TTC-027强烈下调。tRF-Glu-TTC-027的过表达抑制了GC的恶性活性。通过蛋白质免疫印迹法证实MAPK信号通路是GC中tRF-Glu-TTC-027的靶标通路。这是第一项表明tRF-Glu-TTC-027是一种新的肿瘤抑制因子且可能成为GC分子靶向治疗潜在靶点的研究。