Disruption of cellular plasticity by repeat RNAs in human pancreatic cancer Journal Article
| Authors: | You, E.; Danaher, P.; Lu, C.; Sun, S.; Zou, L.; Phillips, I. E.; Rojas, A. S.; Ho, N. I.; Song, Y.; Raabe, M. J.; Xu, K. H.; Richieri, P. M.; Li, H.; Aston, N.; Porter, R. L.; Patel, B. K.; Nieman, L. T.; Schurman, N.; Hudson, B. M.; North, K.; Church, S. E.; Deshpande, V.; Liss, A. S.; Kim, T. K.; Cui, Y.; Kim, Y.; Greenbaum, B. D.; Aryee, M. J.; Ting, D. T. |
| Article Title: | Disruption of cellular plasticity by repeat RNAs in human pancreatic cancer |
| Abstract: | Aberrant expression of repeat RNAs in pancreatic ductal adenocarcinoma (PDAC) mimics viral-like responses with implications on tumor cell state and the response of the surrounding microenvironment. To better understand the relationship of repeat RNAs in human PDAC, we performed spatial molecular imaging at single-cell resolution in 46 primary tumors, revealing correlations of high repeat RNA expression with alterations in epithelial state in PDAC cells and myofibroblast phenotype in cancer-associated fibroblasts (CAFs). This loss of cellular identity is observed with dosing of extracellular vesicles (EVs) and individual repeat RNAs of PDAC and CAF cell culture models pointing to cell-cell intercommunication of these viral-like elements. Differences in PDAC and CAF responses are driven by distinct innate immune signaling through interferon regulatory transcription factor 3 (IRF3). The cell-context-specific viral-like responses to repeat RNAs provide a mechanism for modulation of cellular plasticity in diverse cell types in the PDAC microenvironment. © 2024 Elsevier Inc. |
| Keywords: | signal transduction; controlled study; protein expression; unclassified drug; genetics; nonhuman; pancreas cancer; pancreatic neoplasms; mouse; metabolism; stat3 protein; gene expression; interleukin 10; carcinoma, pancreatic ductal; small interfering rna; immunoglobulin enhancer binding protein; caspase 3; immunofluorescence; pathology; cell line, tumor; transcriptomics; enzyme linked immunosorbent assay; alpha smooth muscle actin; rna; gene expression regulation; gene expression regulation, neoplastic; pancreas tumor; tumor cell line; western blotting; immunoblotting; innate immunity; immunity, innate; glyceraldehyde 3 phosphate dehydrogenase; pancreatic cancer; myofibroblast; ribosome rna; doxycycline; cxcl2 chemokine; rna extraction; rna sequence; tumor microenvironment; open reading frame; transmission electron microscopy; cancer associated fibroblast; epithelial mesenchymal transition; exosome; myofibroblasts; pancreatic ductal carcinoma; janus kinase 1; interferon regulatory factor 7; cell disruption; interferon regulatory factor 3; interleukin 11; cell plasticity; interferon regulatory factor-3; cellular plasticity; sanger sequencing; cancer-associated fibroblast; humans; cancer-associated fibroblasts; human; article; long untranslated rna; extracellular vesicles; long interspersed nuclear element 1; repeat rna; metastasis associated lung adenocarcinoma transcript 1; nuclear paraspeckle assembly transcript 1; irf3 protein, human; open reading frame 2; retrotransposon open reading frame 1 |
| Journal Title: | Cell |
| Volume: | 187 |
| Issue: | 25 |
| ISSN: | 0092-8674 |
| Publisher: | Cell Press |
| Date Published: | 2024-12-11 |
| Start Page: | 7232 |
| End Page: | 7247.e23 |
| Language: | English |
| DOI: | 10.1016/j.cell.2024.09.024 |
| PUBMED: | 39383862 |
| PROVIDER: | scopus |
| PMCID: | PMC11645244 |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
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