An integrative virtual screening model for targeting miRNA-mRNA interaction to block translation of mRNA
Refereed conference paper presented and published in conference proceedings


摘要Few attempts have been made to develop strategies for screening small molecule therapeutics targeting mature miRNAs. To address the issue, we constructed an integrative virtual screening model (natural products) for targeting the loop motifs in miRNA-mRNA interaction. Recently, we have found that miR-214 could target mRNA of ATF4 to inhibit osteoblastic bone formation. By using our model to screen the specific candidates targeting miR-214-ATF4 mRNA interaction, a list of potential candidates was selected. Among them, the small molecule #4 (isolated from Epimedium Herb) with the highest score, could bind to miR-214-ATF4 loop, as evidenced by the LC-MS data. The small molecule #4 promoted ATF4 protein expression and osteogenic potential. The docking data predicted that the 5-hydroxy group of the small molecule #4 could form hydrogen bonds with both A10 and U14 of the loop. Further, the LC-MS data demonstrated that the mutation of A10 and U14 could reduce the binding between the small molecule #4 and the mutated loop. Moreover, the osteogenic potential of the small molecule #4 was inhibited after the transfection of the loop, whereas no significant change was found after the transfection of the mutated loop. Meanwhile, the destruction of the 5-hydroxy group of the small molecule #4 could reduce the binding between the modified small molecule #4 and the loop, but also inhibit the osteogenic potential. Thus, the small molecule #4 could target miRNA-214-ATF4 mRNA interaction to block repression inhibition of ATF4 and promote bone formation. Our current model could provide a potential strategy in discovering small molecules (especially natural products) specifically targeting miRNA-mRNA with accuracy for clinical translation in specific diseases.
著者Zhenjian Zhuo, Zong-Kang Zhang, Daogang Guan, Chao Liang, Aiping Lu, Ge Zhang, Bao-Ting Zhang
會議名稱2018 Chinese Medical Graduates Tournament

上次更新時間 2020-28-04 於 16:39