LncRNA SNHG16 reverses the effects of miR-15a/16 on LPS-induced inflammatory pathway

• Published in: Biomedicine & pharmacotherapy Vol. 106; pp. 1661 - 1667
• Main Authors: Wang, Wenying, Lou, Chunyan, Gao, Jie, Zhang, Xiaomin, Du, Yaowu
• Format: Journal Article
• Language: English
• Published: France Elsevier Masson SAS 01.10.2018
• Subjects: Animals; Case-Control Studies; Down-Regulation; HEK293 Cells; Humans; Infant, Newborn; Lipopolysaccharides - pharmacology; Macrophages - drug effects; Macrophages - metabolism; Mice; MicroRNAs - genetics; MicroRNAs - metabolism; miR-15a/16; Neonatal sepsis; Neonatal Sepsis - blood; Neonatal Sepsis - diagnosis; Neonatal Sepsis - genetics; RAW 264.7 Cells; RNA, Long Noncoding - blood; RNA, Long Noncoding - genetics; RNA, Long Noncoding - metabolism; Signal Transduction - drug effects; SNHG16; TLR4; Toll-Like Receptor 4 - genetics; Toll-Like Receptor 4 - metabolism; SNHG16; miR-15a/16; TLR4; Neonatal sepsis
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2018.07.105

[Display omitted] •LncRNA SNHG16 can downregulate the expression levels of miR-15a/16.•TLR4 is a target gene of miR-15a/16.•SNHG16 regulate TLR4 by binding with miR-15a/16 in RAW264.7 cells.•SNHG16 reverses the effects of miR-15a/16 overexpression on the LPS-promoted TLR-4 signal. Nowadays, neonatal sepsis has gradually become a global problem for its high incidence and increasing mortality. Previous studies have reported that miR-15a and miR-16 are two important modulators in neonatal sepsis. However, the upstream molecular mechanism of miR-15a/16 cluster is still mysterious. This study aims to explore a lncRNA can bind with miR-15a/16 in neonatal sepsis. Microarray analysis helped us found top ten lncRNAs which were downregulated in neonatal sepsis serum. Among these ten lncRNAs, SNHG16 was uncovered to significantly downregulated both miR-15a and miR-16. According to the result of subcellular fractionation assay, SNHG16 was mainly located in the cytoplasm of RAW264.7 cell, indicating the potential ceRNA role of SNHG16. Mechanism investigations revealed that SNHG16 could act as a ceRNA to upregulate TLR4 which is the target mRNA of miR-15a/16 cluster. At last, rescue assays demonstrated that SNHG16 reversed the effects of miR-15a/16 on LPS-induced inflammatory pathway. In summary, SNHG16 can act as a ceRNA to modulate miR-15a/16 cluster, thereby affecting LSP-induced inflammatory pathway which was downregulated by miR-15a/16 cluster.