Zheng Hongrui, Wang Juan, Zhang Wenjie, He Bin, Wang Yunhua, Zhang Xiaotong, Mao Hui, Fan Lei
Department of Orthopedics, The Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, China.
Department of Ultrasonic Diagnosis, The Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, China.
J Biomed Nanotechnol. 2022 Feb 1;18(2):453-462. doi: 10.1166/jbn.2022.3256.
Bioactive nanomaterial circular RNA (circRNA) is an important non-coding RNA with a strong specificity, stable structure and high expression abundance. It can affect many diseases and physiological processes and may become a new way of disease diagnosis and targeted therapy. Recent studies have shown that Staphylococcal Nuclease Domain-Containing Protein 1 (SND1) can recognize N6-methyladenine (M6A) modified mRNA and regulate target mRNA stability. It can then control the expression of a series of downstream genes. However, whether SND1 can directly combine with circRNA and regulate its stability and function are new issues to be discussed. Results showed bioactive nanomaterial circ0024831 could directly bind to the Tudor domain of SND1 in the cytoplasm to block the recognition of SND1 to M6A modified RNA thus reducing the stability of downstream target gene mRNA and inhibiting the expression of downstream regulatory proteins. The down-regulation of circ0024831 expression in osteosarcoma cells relieved inhibition of SND1 which lead to change of tumor-related gene expression profile, promoting the occurrence and development of osteosarcoma.
生物活性纳米材料环状RNA（circRNA）是一种重要的非编码RNA，具有很强的特异性、稳定的结构和高表达丰度。它可以影响多种疾病和生理过程，可能成为疾病诊断和靶向治疗的新途径。最近的研究表明，含葡萄球菌核酸酶结构域蛋白1（SND1）可以识别N6-甲基腺嘌呤（M6A）修饰的mRNA并调节靶mRNA的稳定性。进而控制一系列下游基因的表达。然而，SND1是否能直接与circRNA结合并调节其稳定性和功能是有待探讨的新问题。结果表明，生物活性纳米材料circ0024831可以在细胞质中直接与SND1的Tudor结构域结合，阻断SND1对M6A修饰RNA的识别，从而降低下游靶基因mRNA的稳定性并抑制下游调节蛋白的表达。骨肉瘤细胞中circ0024831表达的下调减轻了对SND1的抑制，导致肿瘤相关基因表达谱的改变，促进骨肉瘤的发生和发展。
