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微小 RNA 转录物 1(MIAT)通过海绵吸附 miR-342-3p/性别决定区 Y 框蛋白 6(SOX6)轴促进口腔黏膜下纤维性变中成纤维细胞的肌成纤维细胞活性和转化。

MIAT promotes myofibroblastic activities and transformation in oral submucous fibrosis through sponging the miR-342-3p/SOX6 axis.

机构信息

School of Dentistry, Chung Shan Medical University, Taichung, Taiwan.

Department of Dentistry, Chung Shan Medical University Hospital, Taichung, Taiwan.

出版信息

Aging (Albany NY). 2024 Oct 7;16(19):12909-12927. doi: 10.18632/aging.206121.

Abstract

Oral submucous fibrosis (OSF) is an oral potentially malignant disorder that is closely related to the habit of areca nut chewing. Long non-coding RNA (lncRNA) myocardial infarction-associated transcript () has been identified as an essential regulator in the fibrosis progression. However, the role of in the development of OSF remains unknown. The transcriptomic profile showed that is significantly overexpressed in the OSF cohort, with a positive correlation to fibrotic markers. The silencing of expression in primary buccal mucosal fibroblasts (BMFs) markedly inhibited arecoline-induced myofibroblast transformation. Mechanistically, functioned as a sponge and suppressed the inhibitory effect of on mRNA, thereby reinstating expression. Subsequent RNA expression rescue experiments confirmed that enhanced resistance to apoptosis and facilitated myofibroblastic properties such as cell mobility and collagen gel contraction by regulating the axis. Taken together, these results suggest that the abnormal upregulation of is important in contributing persistent activation of myofibroblasts in fibrotic tissue, which may result from prolonged exposure to the constituents of areca nut. Furthermore, our findings demonstrated that therapeutic avenues that target the axis may be a promising approach for OSF treatments.

摘要

口腔黏膜下纤维性变(OSF)是一种与槟榔咀嚼习惯密切相关的口腔潜在恶性疾病。长链非编码 RNA(lncRNA)心肌梗塞相关转录物()已被确定为纤维化进展的重要调节因子。然而,在 OSF 的发展中,的作用尚不清楚。转录组谱显示,在 OSF 队列中显著过表达,与纤维化标志物呈正相关。在原代颊黏膜成纤维细胞(BMFs)中沉默表达可显著抑制槟榔碱诱导的肌成纤维细胞转化。机制上,作为海绵吸附并抑制对 mRNA 的抑制作用,从而恢复表达。随后的 RNA 表达挽救实验证实,通过调节轴,增强了对细胞凋亡的抵抗能力,并促进了细胞迁移和胶原凝胶收缩等成肌纤维特性。总之,这些结果表明,的异常上调在纤维化组织中持续激活肌成纤维细胞中起重要作用,这可能是由于长期暴露于槟榔的成分。此外,我们的研究结果表明,针对轴的治疗方法可能是治疗 OSF 的一种有前途的方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1bf7/11501384/87c8d7f41a51/aging-16-206121-g001.jpg

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