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| Identification of a Novel TAR RNA-Binding Protein 2 Modulator with Potential Therapeutic Activity against Hepatocellular Carcinoma | |
Zhou,Zongyuan; Li,Yiming; Ma,Xiaofang; Cao,Biyun; Peng,Ting; Sheng,Yuwen; Peng,Huipan; Li,Runze; Cao,Yu; Xi,Ruiying; Li,Fu; Wang,Mengru; Sun,Handong ; Zhang,Guolin; Zhang,Hongbin; Hu,Kaifeng; Xiao,Weilie; Wang,Fei
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| 2021 | |
| Source Publication | JOURNAL OF MEDICINAL CHEMISTRY
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| ISSN | 0022-2623 |
| Volume | 64Issue:11Pages:7404-7421 |
| Abstract | Imbalance miRNAs contribute to tumor formation; therefore, the development of small-molecule compounds that regulate miRNA biogenesis is an important strategy in oncotherapy. Here, (-)-Gomisin M1 (GM) was found to modulate miRNA biogenesis to inhibit the proliferation, migration, and invasion of hepatocellular carcinoma (HCC) cells. GM modulated expression profiles of miRNA and protein in HCC cells and suppressed tumor growth in a mouse model. Mechanistically, GM affected miRNA maturation by targeting TAR RNA-binding protein 2 (TRBP), with an efficacy higher than that of enoxacin, and promoted the binding of TRBP with Dicer. Structural simplification and a preliminary structure-activity relationship study via the synthesis of 20 GM derivatives showed that compound 9 exhibited more potent inhibitory activity in HCC cell proliferation and affinity for TRBP than did GM. These results suggest that TRBP may be a novel potential therapeutic target in HCC and compound 9 may be a potential drug candidate for the treatment of HCC. |
| Keyword | GOMISIN-A DIBENZOCYCLOOCTADIENE LIGNANS SCHISANDRA-CHINENSIS MASS-SPECTROMETRY MIRNA EXPRESSION DOWN-REGULATION NONCODING RNA MICRORNA LIVER DICER |
| DOI | 10.1021/acs.jmedchem.1c00018 |
| WOS ID | WOS:000662187100020 |
| Citation statistics | |
| Document Type | 期刊论文 |
| Identifier | http://ir.kib.ac.cn/handle/151853/73264 |
| Collection | 中国科学院昆明植物研究所 |
| Affiliation | 1.Chinese Acad Sci, Ctr Nat Prod Res, Chengdu Inst Biol, Chengdu 610041, Peoples R China 2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 3.Yunnan Univ, Yunnan Res & Dev Ctr Nat Prod, Sch Chem Sci & Technol, Minist Educ,Key Lab Med Chem Nat Resource, Kunming 650091, Yunnan, Peoples R China 4.Chengdu Univ Tradit Chinese Med, Innovat Inst Chinese Med & Pharm, Chengdu 611137, Peoples R China 5.Chinese Acad Sci, Kunming Inst Bot, State Key Lab Phytochem & Plant Resources West Ch, Kunming 650201, Yunnan, Peoples R China 6.Chinese Acad Sci, Xiongan Inst Innovat, Baoding 071700, Hebei, Peoples R China |
| Recommended Citation GB/T 7714 | Zhou,Zongyuan,Li,Yiming,Ma,Xiaofang,et al. Identification of a Novel TAR RNA-Binding Protein 2 Modulator with Potential Therapeutic Activity against Hepatocellular Carcinoma[J]. JOURNAL OF MEDICINAL CHEMISTRY,2021,64(11):7404-7421. |
| APA | Zhou,Zongyuan.,Li,Yiming.,Ma,Xiaofang.,Cao,Biyun.,Peng,Ting.,...&Wang,Fei.(2021).Identification of a Novel TAR RNA-Binding Protein 2 Modulator with Potential Therapeutic Activity against Hepatocellular Carcinoma.JOURNAL OF MEDICINAL CHEMISTRY,64(11),7404-7421. |
| MLA | Zhou,Zongyuan,et al."Identification of a Novel TAR RNA-Binding Protein 2 Modulator with Potential Therapeutic Activity against Hepatocellular Carcinoma".JOURNAL OF MEDICINAL CHEMISTRY 64.11(2021):7404-7421. |
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