通过METTL3介导的m6pri-miRNA-31的修改促进了缩性痕进展
Qirui Wang1, Jialin Hou1, Siyi Zeng1
1Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China.
Acta biochimica et biophysica Sinica
|March 20, 2025
概括
在高变性痕 (HS) 中,METTL3和m6A甲基化升高. 通过调节miR-31-5p和ZBTB20的方法,METTL3 knockdown抑制了HS纤维细胞纤维化,这表明HS的治疗标.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 皮肤病学 皮肤病学
背景情况:
- 过度缩性痕 (HS) 标志着皮肤过度纤维化.
- 异常的N6-甲基氨酸 (m6A) 修饰模式与HS有关,但甲基转移酶METTL3的作用尚不清楚.
研究的目的:
- 调查METTL3在HS病变发生过程中的作用和分子机制.
- 为了确定HS的潜在治疗点.
主要方法:
- 西部涂抹测试用于评估METTL3蛋白水平.
- 在HS衍生纤维细胞 (HSFBs) 中,shRNA介导的METTL3的淘汰.
- MeRIP-seq用于识别m6A修改位点.
- 传染的miR-31-5p模仿和ZBTB20的淘汰.
主要成果:
- 在HS中,METTL3蛋白和m6A水平受到上调.
- 在HSFB中,METTL3的抑制降低了原和α-SMA的表达,抑制了增殖和迁移,并诱导了G1细胞周期停止.
- 在pri-miR-31上发现了m6A修饰,METTL3的淘汰增加了pri-miR-31并减少了成熟的miR-31-5p.
- miR-31-5p模仿部分逆转了m6A抑制剂的作用.
- ZBTB20被确定为miR-31-5p的下游标,其敲击抑制了纤维细胞纤维化.
结论:
- METTL3/m6A pri-miR-31/ZBTB20通路的表观遗传调节有助于HS纤维化.
- 这一途径代表了治疗缩性痕的潜在治疗标.
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