Department of Clinical Laboratory, Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research &The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, 210009, China.
Department of B-Ultrasound Room, Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research &The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, 210009, China.
Cancer Lett. 2019 Aug 10;457:60-73. doi: 10.1016/j.canlet.2019.05.007. Epub 2019 May 9.
tRNA-derived fragments offer a recently identified group of non-coding single-stranded RNAs that are often as abundant as microRNAs in cancer cells and play important roles in carcinogenesis. However, the biological functions of them in breast cancer are still unclear. Hence, we focused on investigating whether tiRNAs could play a key role in the progression of breast cancer. We have identified 5'-tiRNA with significantly low expression in breast cancer tissues. The down-regulation of serum 5'-tiRNA was positively correlated with stage progression and lymph node metastasis. Overexpression of 5'-tiRNA suppressed cells malignant activities. FZD3 was confirmed to be a direct target of 5'-tiRNA in breast cancer. In addition, FZD3, β-Catenin, c-myc and cyclinD1 levels in 5'-tiRNA overexpressing cells were downregulated while APC was inversely upregulated. Moreover, 5'-tiRNA inhibited the FZD3-mediated Wnt/β-Catenin signaling pathway in breast cancer cells. Finally, 5'-tiRNA levels differentiated breast cancer from healthy controls with a sensitivity of 90.0% and specificity of 62.7%. This is the first study to show that 5'-tiRNA as a new tumor-suppressor through inhibition of FZD3/Wnt/β-Catenin signaling pathway, which could be as a potential diagnostic biomarker for breast cancer.
tRNA 衍生片段提供了一组最近被识别的非编码单链 RNA，它们在癌细胞中的丰度通常与 microRNAs 相当，在致癌作用中发挥重要作用。然而，它们在乳腺癌中的生物学功能尚不清楚。因此，我们专注于研究 tiRNA 是否在乳腺癌的进展中发挥关键作用。我们已经鉴定出在乳腺癌组织中表达明显降低的 5'-tiRNA。血清 5'-tiRNA 的下调与肿瘤分期进展和淋巴结转移呈正相关。5'-tiRNA 的过表达抑制了细胞的恶性活动。FZD3 被证实是乳腺癌中 5'-tiRNA 的直接靶标。此外，在 5'-tiRNA 过表达的细胞中，FZD3、β-连环蛋白、c-myc 和 cyclinD1 水平下调，而 APC 则相反上调。此外，5'-tiRNA 抑制了乳腺癌细胞中 FZD3 介导的 Wnt/β-连环蛋白信号通路。最后，5'-tiRNA 水平能够以 90.0%的灵敏度和 62.7%的特异性区分乳腺癌和健康对照者。这是第一项表明 5'-tiRNA 通过抑制 FZD3/Wnt/β-连环蛋白信号通路作为新的肿瘤抑制因子的研究，它可能成为乳腺癌的潜在诊断生物标志物。
