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Pan-cancer analysis of microRNA expression profiles highlights microRNAs enriched in normal body cells as effective suppressors of multiple tumor types: A study based on TCGA database

Moradi, S ; Sharif University of Technology | 2022

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  1. Type of Document: Article
  2. DOI: 10.1371/journal.pone.0267291
  3. Publisher: Public Library of Science , 2022
  4. Abstract:
  5. Background MicroRNAs (miRNAs) are frequently deregulated in various types of cancer. While antisense oligonucleotides are used to block oncomiRs, delivery of tumour-suppressive miRNAs holds great potential as a potent anti-cancer strategy. Here, we aim to determine, and functionally analyse, miRNAs that are lowly expressed in various types of tumour but abundantly expressed in multiple normal tissues. Methods The miRNA sequencing data of 14 cancer types were downloaded from the TCGA dataset. Significant differences in miRNA expression between tumor and normal samples were calculated using limma package (R programming). An adjusted p value < 0.05 was used to compare normal versus tumor miRNA expression profiles. The predicted gene targets were obtained using TargetScan, miRanda, and miRDB and then subjected to gene ontology analysis using Enrichr. Only GO terms with an adjusted p < 0.05 were considered statistically significant. All data from wet-lab experiments (cell viability assays and flow cytometry) were expressed as means ± SEM, and their differences were analyzed using GraphPad Prism software (Student’s t test, p < 0.05). Results By compiling all publicly available miRNA profiling data from The Cancer Genome Atlas (TCGA) Pan-Cancer Project, we reveal a small set of tumour-suppressing miRNAs (which we designate as’normomiRs’) that are highly expressed in 14 types of normal tissues but poorly expressed in corresponding tumour tissues. Interestingly, muscle-enriched miRNAs (e.g. miR-133a/b and miR-206) and miRNAs from DLK1-DIO3 locus (e.g. miR-381 and miR-411) constitute a large fraction of the normomiRs. Moreover, we define that the CCCGU motif is absent in the oncomiRs’ seed sequences but present in a fraction of tumour-suppressive miRNAs. Finally, the gain of function of candidate normomiRs across several cancer cell types indicates that miR-206 and miR-381 exert the most potent inhibition on multiple cancer types in vitro. Conclusion Our results reveal a pan-cancer set of tumour-suppressing miRNAs and highlight the potential of miRNA-replacement therapies for targeting multiple types of tumour. © 2022 Moradi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
  6. Keywords:
  7. MicroRNA 100 ; MicroRNA 106b ; MicroRNA 1247 ; MicroRNA 1301 ; MicroRNA 1307 ; MicroRNA 130b ; MicroRNA 133a ; MicroRNA 133b ; MicroRNA 155 ; MicroRNA 15a ; MicroRNA 16 ; MicroRNA 17 ; MicroRNA 181 ; MicroRNA 19a ; MicroRNA 206 ; MicroRNA 20a ; MicroRNA 21 ; MicroRNA 3127 ; MicroRNA 381 ; MicroRNA 411 ; MicroRNA 454 ; MicroRNA 589 ; MicroRNA 629 ; MicroRNA 671 ; MicroRNA 769 ; MicroRNA 93 ; MicroRNA 937 ; MicroRNA 99a ; Normo microRNA ; Unclassified drug ; MicroRNA ; MIRN206 microRNA, human ; MIRN381 microRNA, human ; MIRN411 microRNA, human ; 3' untranslated region ; A-549 cell line ; Cancer inhibition ; Cancer tissue ; Carcinogenesis ; Carcinogenicity ; Cell viability assay ; Computer model ; DLK1 DIO3 gene ; Flow cytometry ; Gain of function mutation ; Gene expression profiling ; Gene locus ; Gene regulatory network ; Gene replacement therapy ; Gene sequence ; Genetic database ; Genetic profile ; Genetic transfection ; Human ; In vitro study ; LNCaP cell line ; MAPK signaling ; MDA-MB-231 cell line ; Multiple tumor ; Oncogene ; PC-3 [Human prostate carcinoma] cell line ; RNA analysis ; RNA sequencing ; SK-OV-3 cell line ; Tumor suppressor gene ; Upregulation ; Factual database ; Gene expression regulation ; Genetics ; Metabolism ; Neoplasm ; Databases, Factual ; Gene Expression Regulation, Neoplastic ; Gene Ontology ; Humans ; MicroRNAs ; Neoplasms
  8. Source: PLoS ONE ; Volume 17, Issue 4 April , 2022 ; 19326203 (ISSN)
  9. URL: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0267291