Long non-coding RNA MALAT1 promotes odontogenic differentiation of human dental pulp stem cells by impairing microRNA-140-5p-dependent downregulation of GIT2.

Abstract

Accumulating research continues to highlight the notable role of microRNAs (miRs) and long non-coding RNAs (lncRNAs) as important regulators in the process of human dental pulp stem cell (hDPSCs) differentiation. The current study aimed to investigate the novel regulatory circuitry of lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1)/miR-140-5p/G protein-coupled receptor (GPCR)-kinase 2 interacting protein 2 (GIT2) on the odontogenic differentiation of hDPSCs. In hDPSCs, miR-140-5p was downregulated during the odontogenic differentiation, which was verified to directly target GIT2. RNA crosstalk determined by dual-luciferase reporter and RNA pull-down assays revealed that MALAT1 could bind to miR-140-5p to upregulate the expression of GIT2. After that, the levels of MALAT1, miR-140-5p, and GIT2 in hDPSCs were up- or downregulated by exogenous transfection or lentivirus infection in order to investigate their effects on the differentiation of hDPSCs. It was observed that elevation of miR-140-5p or knockdown of GIT2 resulted in inhibited alkaline phosphatase (ALP) activity, expression of dentin sialophosphoprotein (DSPP), dentin matrix-protein-1 (DMP-1), and distal-less homeobox 3 (DLX3) as well as positive expression of desmoplakin (DSP) protein. The promotive effects of MALAT1 on odontogenic differentiation were diminished by restoration of miR-140-5p or inhibition of GIT2. Taken together, this study provides valuable evidence suggesting MALAT1 as a potential contributor to the odontogenic differentiation of hDPSCs.