Long non-coding RNA GAS5 protects against Mycoplasma pneumoniaepneumonia by regulating the microRNA-222-3p/TIMP3 axis

Abstract

Mycoplasma pneumoniae pneumonia (MPP) is a type of pneumonia induced by M. pneumoniae (MP) infection. The present study investigated the effect of long non-coding RNA growth arrest-specific 5 (GAS5) in MPP and the underlying molecular mechanism of this. The expression of GAS5, microRNA-222-3p, (miR-222-3p) and tissue inhibitor of metalloproteinases-3 (TIMP3) in MPP was investigated using reverse transcription-quantitative PCR. Lipid-associated membrane protein (LAMP)-induced THP-1 cells were used to model MPP. The viability of LAMP-induced THP-1 cells was analyzed using an MTT assay. Expression levels of interleukin (IL)-1β, IL-6 and tumor necrosis factor-α (TNF-α) pro-inflammatory cytokines, and the anti-inflammatory cytokine heme oxygenase-1 (HO-1) in LAMP-induced THP-1 cells were measured by ELISA. A dual-luciferase reporter assay assessed the associations among GAS5, miR-222-3p and TIMP3. The expression of GAS5 and TIMP3 was downregulated in MPP. Expression of miR-222-3p was upregulated. GAS5-overexpression increased the viability of LAMP-induced THP-1 cells. GAS5 upregulation decreased the levels of IL-1β, IL-6, TNF-α and HO-1 levels in LAMP-induced THP-1 cells. GAS5 directly interacted with miR-222-3p. TIMP3 was a target of miR-222-3p. miR-222-3p upregulation or TIMP3-knockdown reversed the promotion effect on cell viability as well as the inhibitory effect on inflammation caused by GAS5-overexpression in LAMP-induced THP-1 cells. GAS5-overexpression increased the viability and decreased the inflammation of LAMP-induced THP-1 cells by regulating the miR-222-3p/TIMP3 axis. These results demonstrated a potential therapeutic target for MPP treatment.