Department of Orthodontics, School and Hospital of Stomatology, Shandong University & Shandong Provincial Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Jinan, China.
J Cell Mol Med. 2021 May;25(9):4501-4515. doi: 10.1111/jcmm.16541. Epub 2021 Apr 9.
CDR1as is a well-identified circular RNA with regulatory roles in a variety of physiological processes. However, the effects of CDR1as on stemness of periodontal ligament stem cells (PDLSCs) and the underlying mechanisms remain unclear. In this study, we detect CDR1as in human PDLSCs, and subsequently demonstrate that CDR1as maintains PDLSC stemness. Knockdown of CDR1as decreases the expression levels of stemness-related genes and impairs the cell's multi-differentiation and cell migration abilities, while overexpression of CDR1as increases the expression levels of stemness-related genes and enhances these abilities. Furthermore, our results indicate that the RNA-binding protein hnRNPM directly interacts with CDR1as and regulates its expression in PDLSCs. In addition, we show that CDR1as promotes the expression of stemness-related genes in PDLSCs by inhibiting miR-7-mediated suppression of KLF4 expression. Collectively, our results demonstrate that CDR1as participates in the molecular circuitry that regulates PDLSC stemness.
CDR1as 是一种被充分鉴定的环状 RNA,在多种生理过程中具有调节作用。然而,CDR1as 对牙周膜干细胞(PDLSCs)干性的影响及其潜在机制尚不清楚。在本研究中,我们在人牙周膜干细胞中检测到 CDR1as,并进一步证实 CDR1as 维持 PDLSC 的干性。CDR1as 的敲低降低了干性相关基因的表达水平,并损害了细胞的多向分化和细胞迁移能力,而过表达 CDR1as 则增加了干性相关基因的表达水平并增强了这些能力。此外,我们的结果表明,RNA 结合蛋白 hnRNPM 直接与 CDR1as 相互作用,并调节其在 PDLSCs 中的表达。此外,我们表明 CDR1as 通过抑制 miR-7 介导的 KLF4 表达抑制来促进 PDLSCs 中干性相关基因的表达。总之,我们的研究结果表明,CDR1as 参与了调控 PDLSC 干性的分子机制。