Long noncoding RNA SNHG16 targets miR-146a-5p/CCL5 to regulate LPS-induced WI-38 cell apoptosis and inflammation in acute pneumonia.

AIMS

Aberrant expression of the lncRNA small nucleolar RNA host gene 16 (SNHG16) has been researched in multiple cancers and inflammatory diseases. This study was intended to investigate the effect of SNHG16 in vitro model of pneumonia and explore the potential mechanism.

MAIN METHODS

The LPS-induced pulmonary injury model was established in WI-38 human lung fibroblasts cells. SNHG16 and miR-146a-5p expression levels were altered by transfection assay and were evaluated by qRT-PCR. Cell viability and apoptosis were respectively assessed by CCK-8 assay and flow cytometry analysis. The combination of miR-146a-5p and SNHG16 were demonstrated by luciferase reporter assay, RNA immunoprecipitation (RIP) assay and RNA pull-down assay. Associated inflammatory factors expression levels and productions were determined by qRT-PCR, western blotting and Enzyme-linked immunosorbent (ELISA) assay, respectively. Main proteins related apoptosis, c-Jun N-terminal kinase (JNK) pathway and nuclear factor (NF)-κB pathway were also analyzed by western blotting.

KEY FINDINGS

SNHG16 was highly expressed in serum of acute stage pneumonia patients. SNHG16 was up-regulated in LPS-treated WI-38 cell model and SNHG16 knockdown obviously mitigated LPS-induced cell injury by promoting viability, restraining apoptosis and production of inflammatory cytokines. SNHG16 functioned as a competitive endogenous RNA (ceRNA) by efficaciously binding to miR-146a-5p and then restoring CC motif chemokine ligand 5 (CCL5) expression. Besides, miR-146a-5p inhibitor abolished the function of SNHG16 knockdown on cell injury, JNK and NF-κB pathways.

SIGNIFICANCE

SNHG16 regulated LPS-induced inflammation injury in WI-38 cells through competitively binding miR-146a-5p with CCL5 further mediating JNK and NF-κB pathways, which sheds novel light on diagnostics and therapeutics in pneumonia.