肿瘤抑制性微小核糖核酸（miRNA）在癌症发展过程中通常下调。因此，应用合成的miRNA分子恢复被抑制的miRNA，在未来抗癌治疗方面具有创新意义。然而，RNA分子的不稳定性限制了其潜在应用。本篇证明性研究评估了使用合成的化学修饰miRNA分子作为抗癌药物的潜力。含有在3'末端不同位置引入的两种2'-O-RNA修饰，2'-O-甲基和2'-氟衍生物的化学合成miR-1分子被转染到前列腺癌（PC）细胞（LNCaP，PC-3）中。通过定量RT-PCR测量检测性。通过转染的PC细胞的细胞生长动力学研究，探究了miR-1的生长抑制活性与修饰的影响。所有合成修改的miR-1的变异体都可以被转染到PC细胞，并且可以通过RT-PCR检测到。根据化学修饰，尤其是修饰的位置，与合成未修饰的miR-1相比，合成修饰的miR-1的生长抑制活性有所增强。通过化学修饰C2'-OH基团，可以提高合成的miR-1的生物活性。这取决于化学取代基，取代核苷酸的位置和数目。肿瘤抑制性miRNA如miR-1的分子微调可能代表了一种有前途的方法，用于开发多目标靶向的核酸类药物用于癌症治疗。版权所有 © 2023 International Institute of Anticancer Research（Dr. George J. Delinasios）。

Tumor suppressive microRNAs (miR) are frequently down-regulated during cancer development. The application of synthetic miR molecules restoring suppressed miR, therefore, opens up innovative possibilities in future anticancer therapy. The potential application, however, is limited by the instability of RNA molecules. The presented proof-of-principle study evaluates the potential of using synthetic chemically modified miR molecules as anticancer drugs.Chemically synthesized miR-1 molecules containing two 2'-O-RNA modifications, 2'-O-methyl- and 2'-fluoro-derivatives, introduced at different positions of the 3'-terminus, were transfected into prostate cancer (PC) cells (LNCaP, PC-3). Detectability was measured by quantitative RT-PCR. The effect of modifications regarding the growth inhibitory activity of miR-1 was investigated by cell growth kinetics with transfected PC cells.All variants of synthetic modified miR-1 could be transfected into PC cells and were detectable by RT-PCR. Depending on the chemical modification, but especially on the position of the modification, the growth inhibitory activity of synthetic modified miR-1 was increased compared to synthetic unmodified miR-1.Synthetic miR-1 can be enhanced in its biological activity by modification of the C2'-OH group. This depends on the chemical substituent, the position and number of substituted nucleotides. The molecular fine-tuning of tumor suppressive miR like miR-1 may represent a promising approach for the development of multi-targeting nucleic acid-based drugs for cancer therapy.Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.