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

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.

Keywords: Breast cancer; Energy metabolism; LSM1; Single-cell RNA sequencing; Spatial transcriptomics.

MeSH terms

  • Breast Neoplasms* / genetics
  • Female
  • Humans
  • Precision Medicine
  • Proto-Oncogene Proteins / metabolism
  • RNA Cap-Binding Proteins / genetics
  • RNA Cap-Binding Proteins / metabolism
  • RNA, Messenger / metabolism
  • RNA-Binding Proteins / genetics
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae Proteins*
  • Tumor Microenvironment
  • Tumor-Associated Macrophages / metabolism

Substances

  • RNA-Binding Proteins
  • RNA Cap-Binding Proteins
  • Saccharomyces cerevisiae Proteins
  • RNA, Messenger
  • LSM1 protein, human
  • Proto-Oncogene Proteins