Long noncoding RNA MALAT1 modulates sepsis-induced cardiac inflammation through the miR-150-5p/NF-κB axis

Accumulating evidence shows that long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) are involved in the sepsis inflammatory response. However, the involvement of lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1)/miR-150-5p axis in sepsis has not been reported.

Lipopolysaccharide (LPS)-treated H9c2 cells were used to establish a sepsis cell model in vitro. The expressions of MALAT1 and miR-150-5p were monitored using a quantitative reverse transcription polymerase chain reaction (qRT-PCR). An ELISA assay was perfor med to detect the levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). The protein expression of NF-κB was determined by western blot. A luciferase reporter assay was introduced to verify the relationship between MALAT1/miR-150-5p. An RNA immunoprecipitation (RIP) assay and an RNA pull-down assay were carried out to detect the abundance of MALAT1.

MALAT1 was highly expressed, but miR-150-5p was downregulated in LPS-mediated H9c2 cells. Meanwhile, LPS significantly promoted the expressions of IL-6, TNF-α, and NF-κB. MALAT1 depletion attenuated the effect of LPS on the expressions of the inflammatory factors and the NF-κB signaling pathway, which was consistent with that of miR-150-5p overexpression. MALAT1 interacted with miR-150-5p. In addition, the rescue-of-function experiments also indicated that the loss of miR-150-5p undermined the effect of MALAT1 downregulation on H9c2 cells with LPS treatment.

We first demonstrated that MALAT1 depletion is responsible for the sepsis inflammatory response by inhibiting the expressions of IL-6 and TNF-α and the NF-κB signaling pathway by upregulating miR-150-5p.