含有BANCR的细胞外囊泡增强了乳腺癌的抵抗力
Xinming Song1, Shen Liu1, Ying Zeng1
1Department of Head and Neck Oncology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China.
The Journal of biological chemistry
|February 13, 2025
概括
乳腺癌细胞释放带有长非编码RNABANCR的细胞外囊泡 (EV),通过改变细胞通信通路来促进对trastuzumab的耐药性. 抑制BANCR可能会逆转这种抵抗,提供一个新的治疗点.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
背景情况:
- 细胞外囊泡 (EVs) 通过载荷转移调解细胞间通信,包括功能性RNA.
- 乳腺癌 (BC) 细胞可以对关键的向疗法trastuzumab产生耐药性.
- 长非编码RNAs (lncRNAs) 越来越多地被认为对癌症进展和耐药性的作用.
研究的目的:
- 为了研究 lncRNA BRAF 激活的非蛋白质编码RNA (BANCR) 在乳腺癌细胞衍生出来的 EV 中的作用.
- 为了确定受BANCR影响的下游标和分子通路,在耐特苏祖马布乳腺癌中.
主要方法:
- 产生抗逆祖祖马布的乳腺癌细胞 (SKBR-3TR) 并分离它们的EV (SKBR-3TR-EV).
- 在细胞和EV中对EV的表征和BANCR表达的分析.
- 在裸体小鼠中进行了包括细胞共同培养和体内异种移植模型在内的功能研究.
主要成果:
- 在SKBR-3TR细胞及其EV中,BANCR的调节显著上升,与特鲁祖马布耐药性相关.
- SKBR-3TR-EVs将BANCR转移到敏感的SKBR-3细胞中,诱导抵抗.
- 发现BANCR可以抑制miR-34a-5p,从而增加其目标高流动性A1组 (HMGA1) 的表达,并激活Wnt/β-catenin通路.
- 在体内研究表明,抑制BANCR延迟了瘤生长,并恢复了对trastuzumab的敏感性.
结论:
- 携带BANCR的乳腺癌细胞衍生的EVs通过调节miR-34a-5p/HMGA1/Wnt/β-catenin信号轴,有助于对trastuzumab的耐药性.
- 在EVs中的BANCR代表了克服乳腺癌中特鲁苏马布耐药性的潜在治疗标.
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