Department of Gastroenterology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Department of Clinical Laboratory, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, Zhejiang, China.
Cell Death Dis. 2021 Jan 18;12(1):94. doi: 10.1038/s41419-020-03334-8.
Circular RNAs (circRNAs) is one type of important non-coding RNAs that participate in tumorigenesis and cancer progression. In our previous study, we performed a microarray analysis of circRNAs between the tumor tissues and the adjacent normal tissues of hepatocellular carcinoma (HCC) patients, and found that the circRNA hsa_circ_0007456 is significantly downregulated in the tumor tissues and correlated with the prognosis of HCC. We further investigated the relationship between the expression levels of hsa_circ_0007456 in HCC and the susceptibility of NK cells, and found that the expression levels of hsa_circ_0007456 in HCC cell lines significantly influenced their susceptibility to NK cells. Through a series of screening and validation, we found that hsa_circ_0007456 mainly functioned through sponging miR-6852-3p and regulating the expression of intercellular adhesion molecule-1 (ICAM-1) in HCC. The miR-6852-3p/ICAM-1 axis is essential for the NK cytotoxicity toward HCC mediated by hsa_circ_0007456. In conclusion, we identify here hsa_circ_0007456 as a promising biomarker of HCC, and highlight hsa_circ_0007456/miR-6852-3p/ICAM-1 axis as an important signaling pathway in the process of tumor immune evasion and the tumorigenesis of HCC.
环状 RNA（circRNAs）是一种重要的非编码 RNA，参与肿瘤发生和癌症进展。在我们之前的研究中，我们对肝癌（HCC）患者肿瘤组织和相邻正常组织中的 circRNAs 进行了微阵列分析，发现 circRNA hsa_circ_0007456 在肿瘤组织中显著下调，与 HCC 的预后相关。我们进一步研究了 hsa_circ_0007456 在 HCC 中的表达水平与 NK 细胞易感性之间的关系，发现 HCC 细胞系中 hsa_circ_0007456 的表达水平显著影响其对 NK 细胞的敏感性。通过一系列筛选和验证，我们发现 hsa_circ_0007456 主要通过海绵吸附 miR-6852-3p 并调节 HCC 中细胞间黏附分子-1（ICAM-1）的表达来发挥作用。miR-6852-3p/ICAM-1 轴是 hsa_circ_0007456 介导的 NK 细胞对 HCC 细胞毒性所必需的。总之，我们在这里确定 hsa_circ_0007456 是 HCC 的有前途的生物标志物，并强调 hsa_circ_0007456/miR-6852-3p/ICAM-1 轴是肿瘤免疫逃逸和 HCC 发生过程中的重要信号通路。
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