title: Identification of serum microRNA biomarkers for tuberculosis using RNA-seq.
abstract: Tuberculosis (TB) remains a significant human health issue. More effective biomarkers for use in tuberculosis prevention, diagnosis, and treatment, including markers that can discriminate between healthy individuals and those with latent infection, are urgently needed. To identify a set of such markers, we used Solexa sequencing to examine microRNA expression in the serum of patients with active disease, healthy individuals with latent TB, and those with or without prior BCG inoculation. We identified 24 microRNAs that are up-regulated (2.85-1285.93 fold) and 6 microRNAs that are down-regulated (0.003-0.11 fold) (P<0.05) in patients with active TB relative to the three groups of healthy controls. In addition, 75 microRNAs were up-regulated (2.05-2454.58 fold) and 11 were down-regulated (0.001-0.42 fold) (P<0.05) in latent-TB infected individuals relative to BCG- inoculated individuals. Of interest, 134 microRNAs were differentially-expressed in BCG-inoculated relative to un-inoculated individuals (18 up-regulated 2.9-499.29 fold, 116 down-regulated 0.0002-0.5 fold), providing insights into the effects of BCG inoculation at the microRNA level. Target prediction of differentially-expressed microRNAs by microRNA-Gene Network analysis and analysis of pathways affected suggest that regulation of the host immune system by microRNAs is likely to be one of the main factors in the pathogenesis of tuberculosis. qRT-PCR validation indicated that hsa-miR-196b and hsa-miR-376c have potential as markers for active TB disease. The microRNA differential-expression profiles generated in this study provide a good foundation for the development of markers for TB diagnosis, and for investigations on the role of microRNAs in BCG-inoculated and latent-infected individuals.
authors.affiliation: Department of Space Radiobiology, Key Laboratory of Heavy Ion Radiation Biology and Medicine, Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, China ; Key Laboratory of Non-coding RNA, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China ; University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Hongtai
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Beijing Key Laboratory of Drug Resistance in Tuberculosis, Beijing Chest Hospital, Capital Medical University, Beijing, China.
authors.forename: Zhaogang
authors.initials: Z
authors.lastname: Sun
authors.affiliation: Key Laboratory of Non-coding RNA, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
authors.forename: Wenjing
authors.initials: W
authors.lastname: Wei
authors.affiliation: Huazhong Agriculture University, Hubei, China.
authors.forename: Zhonghui
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Key Laboratory of Non-coding RNA, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
authors.forename: Joy
authors.initials: J
authors.lastname: Fleming
authors.affiliation: Key Laboratory of Non-coding RNA, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Zhang
authors.affiliation: College of Life Sciences, Fujian Agriculture and Forestry University, Fuzhou, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Lin
authors.affiliation: Key Laboratory of Non-coding RNA, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Wang
authors.affiliation: Beijing Genomics Institute, Shenzhen 518083, China.
authors.forename: Maoshan
authors.initials: M
authors.lastname: Chen
authors.affiliation: Beijing Key Laboratory of Drug Resistance in Tuberculosis, Beijing Chest Hospital, Capital Medical University, Beijing, China.
authors.forename: Yuhui
authors.initials: Y
authors.lastname: Xu
authors.affiliation: The 4th Peoples' Hospital, Foshan City, Guangdong Province, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Beijing Chest Hospital, Capital Medical University, Beijing, China.
authors.forename: Chuanyou
authors.initials: C
authors.lastname: Li
authors.affiliation: Key Laboratory of Non-coding RNA, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
authors.forename: Lijun
authors.initials: L
authors.lastname: Bi
authors.affiliation: Department of Space Radiobiology, Key Laboratory of Heavy Ion Radiation Biology and Medicine, Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, China.
authors.forename: Guangming
authors.initials: G
authors.lastname: Zhou
mesh_terms: D001483:Base Sequence; D015415:Biomarkers / Q000097:blood*; D002681:China; D017931:DNA Primers / Q000235:genetics; D005786:Gene Expression Regulation / Q000235:genetics*; D006801:Humans; D035683:MicroRNAs / Q000097:blood*; D008969:Molecular Sequence Data; D060888:Real-Time Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D014376:Tuberculosis / Q000097:blood / Q000175:diagnosis*
chemical_list: D015415:Biomarkers; D017931:DNA Primers; C542543:MIRN196 microRNA, human; C573498:MIRN376C microRNA, human; D035683:MicroRNAs