Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Key Laboratory of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang Province, Hangzhou, China.
Cancer Sci. 2022 Oct;113(10):3476-3488. doi: 10.1111/cas.15505. Epub 2022 Aug 16.
Transfer RNA-derived fragments are a group of small noncoding single-stranded RNA that play essential roles in multiple diseases. However, their biological functions in carcinogenesis are not well understood. In this study, 5'tRF-Gly was found to have significantly high expression in hepatocellular carcinoma (HCC), and the upregulation of 5'tRF-Gly was positively correlated with tumor size and tumor metastasis. Overexpression of 5'tRF-Gly induced increased growth rate and metastasis in HCC cells in vitro and in nude mice, while knockdown showed the opposite effect. Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) was confirmed to be a direct target of 5'tRF-Gly in HCC. In addition, the cytological effect of CEACAM1 knockdown proved to be similar to the overexpression of 5'tRF-Gly. Moreover, attenuation of CEACAM1 expression rescued the 5'tRF-Gly-mediated promoting effects on HCC cells. These data show that 5'tRF-Gly is a new tumor-promoting factor and could be a potential diagnostic biomarker or new therapeutic target for HCC.
转移 RNA 衍生片段是一组小的非编码单链 RNA,在多种疾病中发挥着重要作用。然而,它们在致癌作用中的生物学功能尚不清楚。在这项研究中,发现 5'tRF-Gly 在肝细胞癌 (HCC) 中表达水平显著升高,并且 5'tRF-Gly 的上调与肿瘤大小和肿瘤转移呈正相关。5'tRF-Gly 的过表达在体外和裸鼠中诱导 HCC 细胞的生长速度和转移增加,而敲低则表现出相反的效果。癌胚抗原相关细胞黏附分子 1 (CEACAM1) 被确认为 HCC 中 5'tRF-Gly 的直接靶标。此外,CEACAM1 敲低的细胞学效应被证明与 5'tRF-Gly 的过表达相似。此外,降低 CEACAM1 的表达水平可以挽救 5'tRF-Gly 对 HCC 细胞的促进作用。这些数据表明,5'tRF-Gly 是一种新的肿瘤促进因子,可能成为 HCC 的潜在诊断生物标志物或新的治疗靶点。