Alternative polyadenylation of single cells delineates cell types and serves as a prognostic marker in early stage breast cancer.

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  • Additional Information
    • Source:
      Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: eCollection Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE
    • Publication Information:
      Original Publication: San Francisco, CA : Public Library of Science
    • Subject Terms:
      Gene Expression Regulation, Neoplastic* ; Polyadenylation*; 3' Untranslated Regions/*genetics ; Breast Neoplasms/*diagnosis ; Kidney Neoplasms/*diagnosis ; MicroRNAs/*genetics ; RNA, Messenger/*metabolism ; Single-Cell Analysis/*methods; Biomarkers, Tumor/analysis ; Breast Neoplasms/genetics ; Cell Proliferation ; Female ; Gene Expression Profiling ; Humans ; Kidney Neoplasms/genetics ; Prognosis ; RNA, Messenger/genetics ; Sequence Analysis, RNA ; Tumor Microenvironment
    • Abstract:
      Alternative polyadenylation (APA) in 3' untranslated regions (3' UTR) plays an important role in regulating transcript abundance, localization, and interaction with microRNAs. Length-variation of 3'UTRs by APA contributes to efficient proliferation of cancer cells. In this study, we investigated APA in single cancer cells and tumor microenvironment cells to understand the physiological implication of APA in different cell types. We analyzed APA patterns and the expression level of genes from the 515 single-cell RNA sequencing (scRNA-seq) dataset from 11 breast cancer patients. Although the overall 3'UTR length of individual genes was distributed equally in tumor and non-tumor cells, we found a differential pattern of polyadenylation in gene sets between tumor and non-tumor cells. In addition, we found a differential pattern of APA across tumor types using scRNA-seq data from 3 glioblastoma patients and 1 renal cell carcinoma patients. In detail, 1,176 gene sets and 53 genes showed the distinct pattern of 3'UTR shortening and over-expression as signatures for five cell types including B lymphocytes, T lymphocytes, myeloid cells, stromal cells, and breast cancer cells. Functional categories of gene sets for cellular proliferation demonstrated concordant regulation of APA and gene expression specific to cell types. The expression of APA genes in breast cancer was significantly correlated with the clinical outcome of earlier stage breast cancer patients. We identified cell type-specific APA in single cells, which allows the identification of cell types based on 3'UTR length variation in combination with gene expression. Specifically, an immune-specific APA signature in breast cancer could be utilized as a prognostic marker of early stage breast cancer.
      Competing Interests: W.P. is employed by a commercial company, GENINUS Inc. This does not alter our adherence to PLOS ONE policies on sharing data and materials.
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    • Accession Number:
      0 (3' Untranslated Regions)
      0 (Biomarkers, Tumor)
      0 (MicroRNAs)
      0 (RNA, Messenger)
    • Publication Date:
      Date Created: 20190518 Date Completed: 20200129 Latest Revision: 20200309
    • Publication Date:
      20240104
    • Accession Number:
      PMC6524824
    • Accession Number:
      10.1371/journal.pone.0217196
    • Accession Number:
      31100099