RNA结合蛋白LSM7对于RNA剪接至关重要，是剪接体复合物的关键组成部分；然而，其在乳腺癌（BC）中的具体作用尚未得到广泛研究。通过生物信息学分析和免疫组织化学评估了BC样本中LSM7的表达。使用 Transwell 和伤口愈合测定以及原位异种移植模型检查了 LSM7 对促进转移性肿瘤特征的影响。此外，通过 RNA 免疫沉淀和第三代测序探索了 LSM7 在 CD44 选择性剪接中的参与。使用荧光素酶报告基因检测和染色质免疫沉淀进一步阐明了 TCF3 在调节 LSM7 基因表达中的调节作用。我们的研究结果表明，LSM7 在转移性 BC 组织中显着过度表达，并且与 BC 患者的不良预后结果相关。 LSM7过表达显着增加了BC细胞的体外迁移和侵袭能力，并显着促进了体内自发性肺转移。此外，RIP-seq分析显示LSM7与CD44 RNA结合，增强其选择性剪接亚型CD44的表达，从而驱动BC转移和侵袭。此外，转录因子TCF3被发现通过直接结合LSM7的启动子来激活LSM7的转录。总之，本研究强调了LSM7在CD44s亚型的产生和促进乳腺癌转移中的关键作用。靶向 TCF3/LSM7/CD44s 轴可能为乳腺癌治疗提供一种有前景的治疗策略。版权所有 © 2024。由 Elsevier Inc. 出版。

The RNA-binding protein LSM7 is essential for RNA splicing, acting as a key component of the spliceosome complex; however, its specific role in breast cancer (BC) has not been extensively investigated.LSM7 expression in BC samples was evaluated through bioinformatics analysis and immunohistochemistry. The impact of LSM7 on promoting metastatic tumor characteristics was examined using transwell and wound healing assays, as well as an orthotopic xenograft model. Additionally, the involvement of LSM7 in alternative splicing of CD44 was explored via RNA immunoprecipitation and third-generation sequencing. The regulatory role of TCF3 in modulating LSM7 gene expression was further elucidated using luciferase reporter assays and chromatin immunoprecipitation.Our findings demonstrate that LSM7 was significantly overexpressed in metastatic BC tissues and was associated with poor prognostic outcomes in patients with BC. LSM7 overexpression markedly increased the migratory and invasive capabilities of BC cells in vitro and significantly promoted spontaneous lung metastasis in vivo. Furthermore, RIP-seq analysis revealed that LSM7 binded to CD44 RNA, enhancing the expression of its alternatively spliced isoform CD44s, thereby driving BC metastasis and invasion. Additionally, the transcription factor TCF3 was found to activate LSM7 transcription by directly binding to its promoter.In summary, this study highlights the pivotal role of LSM7 in the production of the CD44s isoform and the promotion of breast cancer metastasis. Targeting the TCF3/LSM7/CD44s axis may offer a promising therapeutic strategy for breast cancer treatment.Copyright © 2024. Published by Elsevier Inc.