التفاصيل البيبلوغرافية
العنوان:
AC1MMYR2, an inhibitor of dicer-mediated biogenesis of Oncomir miR-21, reverses epithelial-mesenchymal transition and suppresses tumor growth and progression
المؤلفون:
Kailiang Zhang , Xiaomin Qian , Luyue Chen , Peiyu Pu , Junxia Zhang , Chunsheng Kang , Ji-Long Liu , Ming Yang , Yu Ren , Anling Zhang , Lei Han , Zhendong Shi
المصدر:
Cancer research . 73(17)
سنة النشر:
2013
مصطلحات موضوعية:
Models, Molecular , Ribonuclease III , Cancer Research , Epithelial-Mesenchymal Transition , Blotting, Western , Fluorescent Antibody Technique , Mice, Nude , Antineoplastic Agents , Apoptosis , Breast Neoplasms , Real-Time Polymerase Chain Reaction , Terminal loop , DEAD-box RNA Helicases , Immunoenzyme Techniques , Small Molecule Libraries , Mice , Cell Movement , Stomach Neoplasms , microRNA , Tumor Cells, Cultured , PTEN , Animals , Humans , Neoplasm Invasiveness , Epithelial–mesenchymal transition , RNA, Messenger , In Situ Hybridization, Fluorescence , Cell Proliferation , Regulation of gene expression , Mice, Inbred BALB C , biology , Chemistry , Reverse Transcriptase Polymerase Chain Reaction , Oncomir , Cell biology , Gene Expression Regulation, Neoplastic , MicroRNAs , Pyrimidines , Oncology , Cancer cell , biology.protein , Disease Progression , Female , Glioblastoma , Dicer
الوصف:
The extensive involvement of miRNAs in cancer pathobiology has opened avenues for drug development based on oncomir inhibition. Dicer is the core enzyme in miRNA processing that cleaves the terminal loop of precursor microRNAs (pre-miRNAs) to generate mature miRNA duplexes. Using the three-dimensional structure of the Dicer binding site on the pre-miR-21 oncomir, we conducted an in silico high-throughput screen for small molecules that block miR-21 maturation. By this method, we identified a specific small-molecule inhibitor of miR-21, termed AC1MMYR2, which blocked the ability of Dicer to process pre-miR-21 to mature miR-21. AC1MMYR2 upregulated expression of PTEN, PDCD4, and RECK and reversed epithelial–mesenchymal transition via the induction of E-cadherin expression and the downregulation of mesenchymal markers, thereby suppressing proliferation, survival, and invasion in glioblastoma, breast cancer, and gastric cancer cells. As a single agent in vivo, AC1MMYR2 repressed tumor growth, invasiveness, and metastasis, increasing overall host survival with no observable tissue cytotoxicity in orthotopic models. Our results offer a novel, high-throughput method to screen for small-molecule inhibitors of miRNA maturation, presenting AC1MMYR2 as a broadly useful candidate antitumor drug. Cancer Res; 73(17); 5519–31. ©2013 AACR.
تدمد:
1538-7445
الوصول الحر:
https://explore.openaire.eu/search/publication?articleId=doi_dedup___::afb6b0c52e8e05801520938d525364e2Test https://pubmed.ncbi.nlm.nih.gov/23811941Test
رقم الانضمام:
edsair.doi.dedup.....afb6b0c52e8e05801520938d525364e2
قاعدة البيانات:
OpenAIRE
