在lncRNA MALAT1和DNMT1之间的反循环促进三阴性乳腺癌干和瘤发生
Yu Hu1,2, Yuqiong He1,2, Na Luo1,2
1Department of General Surgery, Xiangya Hospital, Central South University, Changsha, Hunan Province, P.R. China.
Cancer biology & therapy
|August 7, 2023
概括
长非编码RNAMALAT1通过通过miR-137/BCL11A通路降低DNMT1的调节,促进三阴性乳腺癌 (TNBC) 的干性. DNMT1和MALAT1之间的正反循环维持了TNBC的进展.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- 三阴性乳腺癌 (TNBC) 是一种具有有限治疗选择的侵袭性亚型.
- 癌症干细胞 (CSCs) 驱动TNBC瘤发生和治疗耐药性.
- 像MALAT1这样的长非编码RNAs (lncRNAs) 在TNBC干性中的作用正在研究中.
研究的目的:
- 阐明 lncRNA MALAT1 在调节 TNBC 干和瘤发生中的作用.
- 调查MALAT1在TNBC中的作用背后的分子机制.
主要方法:
- 球体和殖民地形成测试以评估茎状性.
- 用于CD44和ALDH表达分析的流细胞计.
- 双硫酸盐测序PCR (BSP) 用于DNA甲基化.
- 在活体中,瘤异种移植模型.
- 双 luciferase 报告员和 RIP 测试以确认RNA 相互作用.
主要成果:
- 在TNBC中,MALAT1和BCL11A被上调,而miR-137和DNMT1被下调.
- 通过向miR-137.1,MALAT1对BCL11A进行了积极调节.
- 马拉特1抑制了DNMT1的表达,增强了TNBC的干和瘤发生.
- 高MALAT1表达与DNMT1介导的低甲基化相关.
- 过度表达DNMT1抑制了TNBC干,这种效应被MALAT1.1逆转.
结论:
- MALAT1通过通过miR-137/BCL11A通路降低DNMT1的调节来增强TNBC干和瘤发生.
- DNMT1和MALAT1之间的积极反循环促进了TNBC的进展.
- 针对MALAT1/DNMT1轴可能为TNBC提供治疗策略.
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