title: Tigecycline Inhibits Glioma Growth by Regulating miRNA-199b-5p-HES1-AKT Pathway.
abstract: Tigecycline is a broad-spectrum, first-in-class glycylcycline antibiotic currently used to treat complicated skin infections and community-acquired pneumonia. However, there is accumulating evidence showing that tigecycline has anticancer properties. In this study, we found tigecycline could inhibit cell proliferation by inducing cell-cycle arrest, but not apoptosis in glioma. To find the underlying mechanism of how tigecycline inhibits cell proliferation, the expression of miRNAs, which were related to regulating cell-cycle progression, was detected with miRNA assay. We found that miR-199b-5p expression was significantly increased after tigecycline treatment, and miR-199b-5p target gene HES1 was downregulated. In addition, the PI3K/AKT pathway was inhibited and p21 expression was increased. When treated with tigecycline and miR-199b-5p antagomir simultaneously in glioma cells, we found that miR-199b-5p antagomir could partly block the effects induced by tigecycline. Tigecycline effectively upregulated miR-199b-5p expression and inhibited tumor growth in the xenograft tumor model of U87 glioma cells. These results suggest that tigecycline may induce cell-cycle arrest and inhibit glioma growth by regulating miRNA-199b-5p-HES1-AKT pathway. Thus, tigecycline is a promising agent in the treatment of malignant gliomas.
authors.affiliation: State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Yi
authors.affiliation: State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Dong
authors.affiliation: Department of Neurosurgery, Daping Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Ouyang
authors.affiliation: Department of Neurosurgery, Daping Hospital, Third Military Medical University, Chongqing, China. Department of Neurosurgery, Second Artillery General Hospital, Chinese People's Liberation Army, Beijing, China.
authors.forename: Ji
authors.initials: J
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Pang
authors.affiliation: State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing, China.
authors.forename: Yanan
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Neurosurgery, Daping Hospital, Third Military Medical University, Chongqing, China. hcui@swu.edu.cn xuliu559@163.com.
authors.forename: Lunshan
authors.initials: L
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing, China. hcui@swu.edu.cn xuliu559@163.com.
authors.forename: Hongjuan
authors.initials: H
authors.lastname: Cui
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D059447:Cell Cycle Checkpoints / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D005910:Glioma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008911:Minocycline / Q000031:analogs & derivatives* / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D034622:RNA Interference; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects*; D000078304:Tigecycline; D000072056:Transcription Factor HES-1 / Q000235:genetics* / Q000378:metabolism; D047368:Tumor Burden
chemical_list: D000970:Antineoplastic Agents; D035683:MicroRNAs; D000072056:Transcription Factor HES-1; C531408:mirn199 microRNA, human; C078493:HES1 protein, human; D000078304:Tigecycline; D051057:Proto-Oncogene Proteins c-akt; D008911:Minocycline