长链非编码RNA（lncRNA）在癌症转移中起着重要作用。探索与转移相关的lncRNA，并开发有效的靶向调控lncRNA功能的策略在转移性癌症的治疗中至关重要，然而这仍然是一个巨大的挑战。在此，我们鉴定出一种新的功能性lncRNA（命名为lncBCMA），通过对抗其泛素化来稳定真核翻译延伸因子1A1（eEF1A1）的表达，促进三阴性乳腺癌（TNBC）的生长和转移。基于这种调控机制，我们构建了一种内体pH响应型纳米颗粒（NP）平台，用于系统输送lncBCMA siRNA（siBCMA）。这种纳米颗粒介导的siBCMA输送能够有效沉默lncBCMA的表达，并促进eEF1A1的泛素化，从而显著抑制TNBC肿瘤的生长和转移。这些发现表明，lncBCMA可以作为预测TNBC患者预后的潜在生物标志物，而纳米颗粒介导的lncBCMA沉默可以成为治疗转移性TNBC的有效策略。 © 2023 中国药学会和中国医学科学院药物研究所。Elsevier B.V.制作和托管。

Long non-coding RNAs (lncRNAs) play an important role in cancer metastasis. Exploring metastasis-associated lncRNAs and developing effective strategy for targeted regulation of lncRNA function in vivo are of utmost importance for the treatment of metastatic cancer, which however remains a big challenge. Herein, we identified a new functional lncRNA (denoted lncBCMA), which could stabilize the expression of eukaryotic translation elongation factor 1A1 (eEF1A1) via antagonizing its ubiquitination to promote triple-negative breast cancer (TNBC) growth and metastasis. Based on this regulatory mechanism, an endosomal pH-responsive nanoparticle (NP) platform was engineered for systemic lncBCMA siRNA (siBCMA) delivery. This NPs-mediated siBCMA delivery could effectively silence lncBCMA expression and promote eEF1A1 ubiquitination, thereby leading to a significant inhibition of TNBC tumor growth and metastasis. These findings show that lncBCMA could be used as a potential biomarker to predict the prognosis of TNBC patients and NPs-mediated lncBCMA silencing could be an effective strategy for metastatic TNBC treatment.© 2023 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.