title: One SNP in the 3'-UTR of HMGB1 gene affects the binding of target bta-miR-223 and is involved in mastitis in dairy cattle.
abstract: High-mobility group box protein 1 (HMGB1) gene has a universal sentinel function for nucleic acid-mediated innate immune responses and acts as a pathogenic mediator in the inflammatory disease. In an effort to identify the functional single-nucleotide polymorphism (SNP) in the 3'-untranslated region (UTR) of the bovine HMGB1 gene that affects the binding to its target microRNA, first, the expression of HMGB1 mRNA in different genotypes and its candidate bta-miR-223 was investigated. Quantitative real-time polymerase chain reaction results showed that the relative expression of HMGB1 mRNA in cows with the genotype GG is significantly higher than those in cows with the genotype AA (P < 0.05). The expression of bta-miR-223 was significantly upregulated by 1.95-fold (P < 0.05) in the bovine mastitis-infected mammary gland tissues compared with that in the healthy tissues. Subsequently, luciferase assay indicated that the HMGB1 expression was directly targeted by bta-miR-223 in human embryo kidney 293 T (HEK 293T) cells. One novel SNP (g. +2776 A > G) in the HMGB1 3'-UTR, altering the binding of HMGB1 and bta-miR-223, was found to be associated with somatic count scores in cows. Taken together, the g. +2776 A > G-GG was an advantageous genotype which can be used as a candidate functional marker for mastitis resistance breeding program.
authors.affiliation: Laboratory of Molecular Genetics and Breeding, Center of Dairy Cattle Research, Shandong Academy of Agricultural Sciences, Industry North Road 159, Jinan, Shandong 250131, People's Republic of China.
authors.forename: Liming
authors.initials: L
authors.lastname: Li
authors.forename: Jinming
authors.initials: J
authors.lastname: Huang
authors.forename: Xiaojian
authors.initials: X
authors.lastname: Zhang
authors.forename: Zhihua
authors.initials: Z
authors.lastname: Ju
authors.forename: Chao
authors.initials: C
authors.lastname: Qi
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Qiuling
authors.initials: Q
authors.lastname: Li
authors.forename: Changfa
authors.initials: C
authors.lastname: Wang
authors.forename: Weiran
authors.initials: W
authors.lastname: Miao
authors.forename: Jifeng
authors.initials: J
authors.lastname: Zhong
authors.forename: Minghai
authors.initials: M
authors.lastname: Hou
authors.forename: Suqin
authors.initials: S
authors.lastname: Hang
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D002417:Cattle; D002478:Cells, Cultured; D019295:Computational Biology; D005260:Female; D024243:HMGB1 Protein / Q000235:genetics*; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D008414:Mastitis, Bovine / Q000235:genetics*; D035683:MicroRNAs / Q000235:genetics*; D008969:Molecular Sequence Data; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012689:Sequence Homology, Nucleic Acid
chemical_list: D020413:3' Untranslated Regions; D024243:HMGB1 Protein; D035683:MicroRNAs; D012333:RNA, Messenger; D008156:Luciferases