An integrative virtual screening model (natural products) for targeting miRNA-mRNA interaction to block translation repression of mRNA: an experimental validation
Refereed conference paper presented and published in conference proceedings


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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, Zongkang Zhang, Baoting Zhang
會議名稱2019 Oligonucleotide and Precision Therapeutics Congress
會議開始日26.03.2019
會議完結日28.03.2019
會議地點Boston
會議國家/地區美國
出版年份2019
語言英式英語

上次更新時間 2020-14-05 於 15:23