title: Burkholderia pseudomallei survival in lung epithelial cells benefits from miRNA-mediated suppression of ATG10.
abstract: Burkholderia pseudomallei is the causative agent of melioidosis, a disease with high mortality, which is prevalent in tropical regions of the world. A recent study shows that B. pseudomallei can survive inside mammalian cells because of its ability to actively evade cell autophagy. However, the underlying mechanisms remain unclear. In the present study, based on microarray screening, we found that ATG10 was downregulated following B. pseudomallei infection in A549 human lung epithelial cells. Forced expression of ATG10 accelerated the elimination of intracellular B. pseudomallei by enhancing the process of autophagy. Moreover, MIR4458, MIR4667-5p, and MIR4668-5p were found, by microarray screening, to be upregulated in response to B. pseudomallei infection. These 3 novel miRNAs, MIR4458, MIR4667-5p, and MIR4668-5p, targeted to the 3'-untranslated region of ATG10 in different time-course and spatial manners. Upregulation of these miRNAs reduced the level of ATG10 and inhibited autophagy, leading to increasing survival rate of intracellular B. pseudomallei. Furthermore, the increase of these miRNAs was correlated with the reduced promoter methylation status in A549 cells in response to B. pseudomallei infection. Our results reveal that 3 novel miRNAs regulate autophagy-mediated elimination of B. pseudomallei by targeting ATG10, and provide potential targets for clinical treatment.
authors.affiliation: a Department of Clinical Microbiology and Immunology ; Southwest Hospital & College of Medical Laboratory Science; Third Military Medical University ; Chongqing , China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Li
authors.forename: Yao
authors.initials: Y
authors.lastname: Fang
authors.forename: Pan
authors.initials: P
authors.lastname: Zhu
authors.forename: Chun-Yan
authors.initials: CY
authors.lastname: Ren
authors.forename: Hai
authors.initials: H
authors.lastname: Chen
authors.forename: Jiang
authors.initials: J
authors.lastname: Gu
authors.forename: Yin-Ping
authors.initials: YP
authors.lastname: Jia
authors.forename: Kun
authors.initials: K
authors.lastname: Wang
authors.forename: Wen-de
authors.initials: WD
authors.lastname: Tong
authors.forename: Wei-Jun
authors.initials: WJ
authors.lastname: Zhang
authors.forename: Jing
authors.initials: J
authors.lastname: Pan
authors.forename: Dong-Shui
authors.initials: DS
authors.lastname: Lu
authors.forename: Bin
authors.initials: B
authors.lastname: Tang
authors.forename: Xu-Hu
authors.initials: XH
authors.lastname: Mao
mesh_terms: D020413:3' Untranslated Regions; D000071183:Autophagy-Related Proteins; D001483:Base Sequence; D016957:Burkholderia pseudomallei / Q000472:pathogenicity*; D002460:Cell Line; D045744:Cell Line, Tumor; D002470:Cell Survival; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000378:metabolism; D019175:DNA Methylation; D004847:Epithelial Cells / Q000166:cytology* / Q000382:microbiology; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D008168:Lung / Q000166:cytology / Q000382:microbiology* / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D018613:Microscopy, Confocal; D046529:Microscopy, Electron, Transmission; D008969:Molecular Sequence Data; D020411:Oligonucleotide Array Sequence Analysis; D010957:Plasmids / Q000378:metabolism; D011401:Promoter Regions, Genetic; D015854:Up-Regulation; D033921:Vesicular Transport Proteins / Q000378:metabolism*
chemical_list: D020413:3' Untranslated Regions; D000071183:Autophagy-Related Proteins; C000607096:MIRN-4458 microRNA, human; C000608360:MIRN4667 microRNA, human; C000608361:MIRN4668 microRNA, human; D035683:MicroRNAs; D033921:Vesicular Transport Proteins; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; C581901:ATG10 protein, human
keywords: ATG10; Burkholderia pseudomallei; DNA methylation; MIR4458; MIR4667-5p; MIR4668-5p; autophagy