MiR-155 inhibits TP53INP1 expression leading to enhanced glycolysis of psoriatic mesenchymal stem cells

Background: Psoriasis is a systemic disease with multiple associated comorbidities, including metabolic syndrome. Studies suggest that chronic inflammation is a central link between psoriasis and metabolic abnormalities. MiR-155 is a well-known microRNA that plays an important regulatory role in inflammation. Studies from our group and others have demonstrated an upregulation of miR-155 in psoriasis.

Objectives: Here, we investigated whether miR-155 regulates glycolysis of psoriasis and the underlying mechanisms.

Methods: Human dermal-derived mesenchymal stem cells (MSC) were treated with miR-155 mimic or inhibitor, followed by assessments of cells proliferation, metabolism and inflammatory response. Target gene prediction and GO/Pathway analysis were used to screen the putative targets involved in the pathways of metabolism, and verified by dual-luciferase reporter assay. To determine whether TP53INP1/p53 signaling pathway is involved in miR-155-mediated regulation of glycolysis, changes in glycolysis were assessed in psoriatic MSC (PM) with either overexpression or knockdown of TP53INP1, or activation/inhibition of p53 signaling pathway.

Results: Our results showed that miR-155 promoted proliferation, migration, inflammatory response and metabolite levels of MSC, while inhibiting apoptosis. In comparison to the MSC from normal subjects, the glycolysis levels were increased in PM. GO and KEGG analyses indicated that TP53INP1 was miR-155 target gene with negative regulation of cellular metabolic process. Moreover, miR-155 promoted glycolysis of PM by negative regulation of TP53INP1/p53 signaling pathway.

Conclusions: MiR-155 could promote glycolysis via targeting of TP53INP1 in PM. These findings suggest a pathogenic role of miR-155 in metabolic abnormalities in psoriasis.