LncRNA NEAT1/miR-875-3p/PPARγ Axis Promotes Mesenchymal Stem Cell Adipogenic Differentiation

Objective: To investigate the effect of Lnc RNA NEAT1 on the adipogenic differentiation of mesenchymal stem cells（MSCs）,and to reveal the mechanism of the effect of NEAT1 on adipogenic differentiation from the perspective of Lnc RNA-mi RNAs-m RNA.The expression of NEAT1 in MSCs derived from patients with aplastic anemia（AA）was analyzed to find a new way to treat this disease.Methods: C57BL/6J mouse,NEAT1 knockout C57BL/6J mouse and human MSCs were isolated and cultured,and MSCs were induced to differentiate into adipocytes.Oil red O staining was performed on the 0d and 10 d of mouse-derived MSCs induced differentiation.The expression of NEAT1 and adipogenic-related markers were detected by q RT-PCR.At the same time,q RT-PCR was used to detect the expression of mi R-875-3p in MSCs derived from C57BL/6J mouse,NEAT1 knockout C57BL/6J mouse,human adipose and bone marrow-derived MSCs treated with sh NC and sh NEAT1.The correlation between the expression of NEAT1 and mi R-875-3p in MSCs from different sources was analyzed to explore the potential mechanism of NEAT1 affecting the adipogenic differentiation of MSCs.Meanwhile,q RT-PCR was used to detect the expressions of NEAT1 and mi R-875-3p in patients with AA and control group,so as to investigate the mechanism of NEAT1 in AA pathogenesis.Results: NEAT1 was upregulated in MSCs adipogenicity,and the adipogenic ability of MSCs was decreased after knockdown and interference of NEAT1 expression.Meanwhile,in MSCs from different sources,the expression of mi R-875-3p was opposite to that of NEAT1.Through the above correlation analysis of the expression of PPARγ,mi R-875-3p and NEAT1,we found significant negative correlation between mi R-875-3p and NEAT1,PPARγ and mi R-875-3p.Meanwhile,we found that NEAT1 expression was increased in AA patients,and mi R-875-3p expression was decreased.Conclusion: NEAT1 is upregulated during the induction and differentiation of mouse and human MSCs into adipocytes.After knocking out or interfering with NEAT1,the adipogenic capacity of MSCs is decreased.The NEAT1—mi R-875-3p axis is involved in the adipogenic differentiation of MSCs by affecting the expression of PPAR-γ.NEAT1 is a promising target for AA therapy.