Institute of Dermatology and Department of Dermatology, No. 1 Hospital, Anhui Medical University, Hefei, Anhui, China; Department of Dermatology and Venereology, Anhui Medical University, Hefei, Anhui, China; State Key Laboratory Incubation Base of Dermatology, Ministry of National Science and Technology, Hefei, Anhui, China.
Int J Biochem Cell Biol. 2013 Nov;45(11):2643-50. doi: 10.1016/j.biocel.2013.09.003. Epub 2013 Sep 11.
microRNA sponges antagonizing the oncogenic microRNAs are potential candidates for RNA-based cancer therapies. Although the constructed sponges so far are to some extent suitable for biological experiments, they can only express at relative low levels in cells, because they are sensitive to microRNA-mediated activation of deadenylation and subsequent exonucleolytic degradation. Since circular RNA molecules are resistant to exonuclease degradation, we report the production of circular microRNA sponges against miR-21 or miR-221 in cell lines using the self-splicing permuted intron-exon sequences derived from T4 bacteriophage gene td. The circularized microRNA sponges withstand enzymatic degradation and are completely resistant to microRNA-mediated degradation. They are more effective than typical linear microRNA sponges and microRNA inhibitors in derepressing microRNA targets. They also display superior anti-cancer activities compared to the linear sponges in malignant melanoma cell lines. We have provided an alternative method for circular microRNA sponge production and malignant melanoma treatment.
针对致癌 microRNA 的 microRNA 海绵拮抗物是基于 RNA 的癌症治疗的潜在候选物。尽管迄今为止构建的海绵在某种程度上适合于生物实验，但它们在细胞中的表达水平相对较低，因为它们易受到 microRNA 介导的去腺苷酸化和随后的外切核酸酶降解的激活。由于环状 RNA 分子不易被外切核酸酶降解，我们报告了使用源自 T4 噬菌体基因 td 的自我剪接置换内含子-外显子序列在细胞系中产生针对 miR-21 或 miR-221 的环状 microRNA 海绵。环化的 microRNA 海绵能够抵抗酶降解，并且完全不受 microRNA 介导的降解的影响。它们比典型的线性 microRNA 海绵和 microRNA 抑制剂在解除 microRNA 靶标抑制方面更有效。与恶性黑素瘤细胞系中的线性海绵相比，它们还显示出优异的抗癌活性。我们提供了一种用于环状 microRNA 海绵产生和恶性黑素瘤治疗的替代方法。
