ArticleFrontiers in immunology2023
Pro-inflammatory polarization and colorectal cancer modulate alternative and intronic polyadenylation in primary human macrophages.
Article in Frontiers in immunology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 15 citations in OpenAlex.
- CFIm25-dependent alternative polyadenylation in AKT2 mRNA programs macrophage polarization.iScience · 2026Article
- Gut microbiota-metabolism axis in digestive tumors: Emerging targets for novel therapies (Review).Experimental and therapeutic medicine · 2026Review
- SRSF12 is a primate-specific splicing factor that induces a tissue-specific gene expression program.Molecular biology of the cell · 2025Article
- APAtizer: a tool for alternative polyadenylation analysis of RNA-Seq data.Bioinformatics (Oxford, England) · 2024Article
- Exploring the complexity of systemic sclerosis etiology by trio whole genome sequencing.Human molecular genetics · 2024Article
- Modulation of diverse biological processes by CPSF, the master regulator of mRNA 3' ends.RNA (New York, N.Y.) · 2024Review
- Integrated Blood Transcriptome and Multi-Tissue Trace Mineral Analyses of Healthy Stocker Cattle Fed Complexed or Inorganic Trace Mineral Supplement.Animals : an open access journal from MDPI · 2024Article
- Non-canonical isoforms of the mRNA polyadenylation factor WDR33 regulate STING-mediated immune responses.Cell reports · 2024Article
- Downregulation of CPSF6 leads to global mRNA 3' UTR shortening and enhanced antiviral immune responses.PLoS pathogens · 2024Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
Introduction: Macrophages are essential cells of the immune system that alter their inflammatory profile depending on their microenvironment. Alternative polyadenylation in the 3'UTR (3'UTR-APA) and intronic polyadenylation (IPA) are mechanisms that modulate gene expression, particularly in cancer and activated immune cells. Yet, how polarization and colorectal cancer (CRC) cells affect 3'UTR-APA and IPA in primary human macrophages was unclear. Methods: In this study, we isolated primary human monocytes from healthy donors, differentiated and polarized them into a pro-inflammatory state and performed indirect co-cultures with CRC cells. ChrRNA-Seq and 3'RNA-Seq was performed to quantify gene expression and characterize new 3'UTR-APA and IPA mRNA isoforms. Results: Our results show that polarization of human macrophages from naïve to a pro-inflammatory state causes a marked increase of proximal polyA site selection in the 3'UTR and IPA events in genes relevant to macrophage functions. Additionally, we found a negative correlation between differential gene expression and IPA during pro-inflammatory polarization of primary human macrophages. As macrophages are abundant immune cells in the CRC microenvironment that either promote or abrogate cancer progression, we investigated how indirect exposure to CRC cells affects macrophage gene expression and 3'UTR-APA and IPA events. Co-culture with CRC cells alters the inflammatory phenotype of macrophages, increases the expression of pro-tumoral genes and induces 3'UTR-APA alterations. Notably, some of these gene expression differences were also found in tumor-associated macrophages of CRC patients, indicating that they are physiologically relevant. Upon macrophage pro-inflammatory polarization, Discussion: Our results reveal new 3'UTR-APA and IPA mRNA isoforms produced during pro-inflammatory polarization of primary human macrophages and CRC co-culture that may be used in the future as diagnostic or therapeutic tools. Furthermore, our results highlight a function for
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