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.

中文翻译：

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长链非编码 RNA MALAT1 通过削弱 GIT2 的 microRNA-140-5p 依赖性下调促进人牙髓干细胞的牙源性分化

越来越多的研究继续强调 microRNAs (miRs) 和长链非编码 RNAs (lncRNAs) 作为重要调节因子在人牙髓干细胞 (hDPSCs) 分化过程中的显着作用。目前的研究旨在研究 lncRNA 转移相关肺腺癌转录物 1 (MALAT1)/miR-140-5p/G 蛋白偶联受体 (GPCR)-激酶 2 相互作用蛋白 2 (GIT2) 对牙源性分化的新型调控回路hDPSCs。在 hDPSCs 中，miR-140-5p 在牙源性分化过程中被下调，这被证实直接靶向 GIT2。通过双荧光素酶报告基因和 RNA 下拉测定确定的 RNA 串扰显示 MALAT1 可以与 miR-140-5p 结合以上调 GIT2 的表达。之后，MALAT1、miR-140-5p、hDPSCs 中的 GIT2 和 GIT2 被外源性转染或慢病毒感染上调或下调，以研究它们对 hDPSCs 分化的影响。观察到 miR-140-5p 的升高或 GIT2 的敲低导致碱性磷酸酶 (ALP) 活性、牙本质唾液酸磷蛋白 (DSPP)、牙本质基质蛋白 1 (DMP-1) 和远端无同源框的表达受到抑制3 (DLX3) 以及桥粒蛋白 (DSP) 蛋白的阳性表达。MALAT1 对牙源性分化的促进作用因 miR-140-5p 的恢复或 GIT2 的抑制而减弱。总之，这项研究提供了有价值的证据，表明 MALAT1 是 hDPSCs 牙源性分化的潜在贡献者。