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Open AccessFeature PaperArticle

Molecular and Functional Characterization of the Somatic PIWIL1/piRNA Pathway in Colorectal Cancer Cells

1
Laboratory of Molecular Medicine and Genomics, Department of Medicine, Surgery and Dentistry “Scuola Medica Salernitana”, University of Salerno, 84081 Baronissi (SA), Italy
2
Genomix4Life srl, Department of Medicine, Surgery and Dentistry “Scuola Medica Salernitana”, University of Salerno, 84081 Baronissi (SA), Italy
3
Medical Genomics Program, Department of Onco-Haematology SS. Giovanni di Dio e Ruggi d’Aragona’ University Hospital, University of Salerno, 84131 Salerno, Italy
*
Authors to whom correspondence should be addressed.
These authors equally contributed to this work.
Cells 2019, 8(11), 1390; https://doi.org/10.3390/cells8111390
Received: 18 September 2019 / Revised: 1 November 2019 / Accepted: 3 November 2019 / Published: 5 November 2019
(This article belongs to the Special Issue Non-coding RNA in Cancer)
PIWI-like (PIWIL) proteins and small non-coding piRNAs, involved in genome regulation in germline cells, are found aberrantly expressed in human tumors. Gene expression data from The Cancer Genome Atlas (TCGA), the Genotype-Tissue Expression (GTEx) project, and the European Genome-Phenome Archive (EGA) indicate that the PIWIL1 gene is ectopically activated in a significant fraction of colorectal cancers (CRCs), where this is accompanied by promoter demethylation, together with germline factors required for piRNA production. Starting from this observation, the PIWIL/piRNA pathway was studied in detail in COLO 205 CRC cells, which express significant levels of this protein, to investigate role and significance of ectopic PIWIL1 expression in human tumors. RNA sequencing and cell and computational biology led to the demonstration that PIWIL1 localizes in a nuage-like structure located in the perinuclear region of the cell and that a significant fraction of the piRNAs expressed in these cells are methylated, and, therefore, present in an active form. This was further supported by RNA immunoprecipitation, which revealed how several piRNAs can be found loaded into PIWIL1 to form complexes also comprising their target mRNAs. The mature transcripts associated with the PIWIL–piRNA complex encode key regulatory proteins involved in the molecular mechanisms sustaining colorectal carcinogenesis, suggesting that the PIWI/piRNA pathway may actively contribute to the establishment and/or maintenance of clinico-pathological features of CRCs. View Full-Text
Keywords: colorectal cancer; small non-coding RNAs; RNA-binding proteins; PIWIL1; piRNAs; nuage compartment; RIP-Seq colorectal cancer; small non-coding RNAs; RNA-binding proteins; PIWIL1; piRNAs; nuage compartment; RIP-Seq
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Sellitto, A.; Geles, K.; D’Agostino, Y.; Conte, M.; Alexandrova, E.; Rocco, D.; Nassa, G.; Giurato, G.; Tarallo, R.; Weisz, A.; Rizzo, F. Molecular and Functional Characterization of the Somatic PIWIL1/piRNA Pathway in Colorectal Cancer Cells. Cells 2019, 8, 1390.

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