口腔粘膜下纤维化（OSF）是一种以炎症和过度胶原沉积为特征的疾病，已被确定为潜在的恶性疾病。最近，一些 microRNA (miRNA) 已被证明与多种与纤维化相关的疾病有关。然而，人们对这些 miRNA 如何调节 OSF 发育知之甚少。因此，本研究旨在鉴定有助于OSF进展的特定miRNA，并探讨其促进纤维化的分子机制。 RNA 测序和 qRT-PCR。采用荧光素酶报告基因活性测定、miRNA模拟物或抑制剂以及短发夹RNA沉默来阐明miRNA的分子机制。采用 Transwell 迁移、胶原收缩和活性氧 (ROS) 生成检测来研究该机制对肌成纤维细胞表型和细胞促纤维化能力的影响。本研究表明 miR-190a 在纤维化的颊粘膜成纤维细胞中过表达。 fBMF）。用 miR-190a 抑制剂转染 fBMF 可减少细胞迁移、胶原凝胶收缩、ROS 生成和纤维化标志物的表达。此外，miR-190a 通过直接结合其靶标 Krüppel 样因子 15 (KLF15) 来发挥这种促纤维化特性。结果还表明，miR-190a的异常上调反过来下调了KLF15的表达，从而导致肌成纤维细胞的激活。我们的研究结果表明，miR-190a参与了肌成纤维细胞的激活，这表明靶向miR-190a /KLF15 轴可能是治疗 OSF 的可行方法。© 2024 中华民国牙科科学协会。 Elsevier B.V. 的出版服务

Oral submucous fibrosis (OSF) is a condition characterized by inflammation and excessive collagen deposition, which has been identified as a potentially malignant disorder. Recently, several microRNAs (miRNAs) have been shown to be implicated in various disorders associated with fibrosis. However, how these miRNAs modulate OSF development is poorly understood. Therefore, the study aimed to identify the specific miRNAs that contribute to the progression of OSF and to investigate their molecular mechanisms in promoting fibrosis.The expression and clinical significance of potential pro-fibrosis miRNA in the OSF cohort and primary buccal mucosal fibroblasts were confirmed through RNA sequencing and qRT-PCR. Luciferase reporter activity assay, miRNA mimic or inhibitor, and short-hairpin RNA silencing were used to elucidate the molecular mechanism of miRNA. Transwell migration, collagen contraction, and reactive oxygen species (ROS) generation detection were used to investigate the effects of this mechanism on the myofibroblast phenotype and cellular pro-fibrosis capacity.This study demonstrated that miR-190a was overexpressed in fibrotic buccal mucosal fibroblasts (fBMFs). Transfecting fBMFs with miR-190a inhibitor resulted in reduced cell migration, collagen gel contraction, ROS generation, and expression of fibrotic markers. Furthermore, miR-190a exerted this pro-fibrosis property by direct binding to its target, Krüppel-like factor 15 (KLF15). The results also indicated that the aberrant upregulation of miR-190a, in turn, downregulated the expression of KLF15, which resulted in the activation of myofibroblast.Our findings demonstrated that miR-190a was involved in myofibroblast activation, suggesting that targeting the miR-190a/KLF15 axis may be a feasible approach in the therapy of OSF.© 2024 Association for Dental Sciences of the Republic of China. Publishing services by Elsevier B.V.