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LSM1 在乳腺癌中的作用:塑造代谢和肿瘤相关巨噬细胞浸润。

The role of LSM1 in breast cancer: Shaping metabolism and tumor-associated macrophage infiltration.

机构信息

Department of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung 813, Taiwan; Institute of Biomedical Sciences, National Sun Yat-sen University, Kaohsiung 804, Taiwan.

Department of Surgery, Kaohsiung Municipal Minsheng Hospital, Kaohsiung 802, Taiwan.

出版信息

Pharmacol Res. 2023 Dec;198:107008. doi: 10.1016/j.phrs.2023.107008. Epub 2023 Nov 22.

Abstract

LSM1 is part of the cytoplasmic protein complex Lsm1-7-Pat1 and is likely involved in pre-mRNA degradation by aiding U4/U6 snRNP formation. More research is needed to uncover LSM1's potential in breast cancer (BRCA) clinical pathology, the tumor immune microenvironment, and precision oncology. We discovered LSM1 as a diagnostic marker for advanced BRCA with poor survival, using a multi-omics approach. We studied LSM1 expression across BRCA regions and its link to immune cells through various methods, including spatial transcriptomics and single-cell RNA-sequencing. We also examined how silencing LSM1 affects mitochondrial function and energy metabolism in the tumor environment. These findings were confirmed using 54 BRCA patient biopsies and tissue microarrays. Immunofluorescence and bioinformatics assessed LSM1's connection to clinicopathological features and prognosis. This study uncovers gene patterns linked to breast cancer, with LSM1 linked to macrophage energy processes. Silencing LSM1 in breast cancer cells disrupts mitochondria and energy metabolism. Spatial analysis aligns with previous results, showing LSM1's connection to macrophages. Biopsies confirm LSM1 elevation in advanced breast cancer with increased macrophage presence. To summarize, LSM1 changes may drive BRCA progression, making it a potential diagnostic and prognostic marker. It also influences energy metabolism and the tumor's immune environment during metastasis, showing promise for precision medicine and drug screening in BRCA.

摘要

LSM1 是细胞质蛋白复合物 Lsm1-7-Pat1 的一部分,可能通过辅助 U4/U6 snRNP 的形成参与 pre-mRNA 的降解。需要进一步的研究来揭示 LSM1 在乳腺癌(BRCA)临床病理学、肿瘤免疫微环境和精准肿瘤学中的潜力。我们使用多组学方法发现 LSM1 是一种与生存不良的晚期 BRCA 相关的诊断标志物。我们研究了 LSM1 在 BRCA 区域的表达及其与免疫细胞的联系,包括空间转录组学和单细胞 RNA 测序。我们还研究了沉默 LSM1 如何影响肿瘤微环境中的线粒体功能和能量代谢。这些发现通过 54 个 BRCA 患者活检和组织微阵列得到了验证。免疫荧光和生物信息学评估了 LSM1 与临床病理特征和预后的关系。这项研究揭示了与乳腺癌相关的基因模式,其中 LSM1 与巨噬细胞的能量过程有关。沉默乳腺癌细胞中的 LSM1 会破坏线粒体和能量代谢。空间分析与之前的结果一致,表明 LSM1 与巨噬细胞有关。活检证实了晚期乳腺癌中 LSM1 的升高,伴随着巨噬细胞的增加。总之,LSM1 的变化可能会推动 BRCA 的进展,使其成为一种潜在的诊断和预后标志物。它还会影响转移过程中的能量代谢和肿瘤的免疫微环境,为 BRCA 的精准医学和药物筛选提供了希望。

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