CRISPRs in the human genome are differentially expressed between malignant and normal adjacent to tumor tissue

Job van Riet, Chinmoy Saha, Nikolaos Strepis, Rutger W.W. Brouwer, Elena S. Martens-Uzunova, Wesley S. van de Geer, Sigrid M.A. Swagemakers, Andrew Stubbs, Yassir Halimi, Sanne Voogd, Arif Mohammad Tanmoy, Malgorzata A. Komor, Youri Hoogstrate, Bart Janssen, Remond J.A. Fijneman, Yashar S. Niknafs, Arul M. Chinnaiyan, Wilfred F.J. van IJcken, Peter J. van der Spek, Guido JensterRogier Louwen*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

Clustered Regularly Interspaced Short Palindromic Repeats (CRISPRs) have been identified in bacteria, archaea and mitochondria of plants, but not in eukaryotes. Here, we report the discovery of 12,572 putative CRISPRs randomly distributed across the human chromosomes, which we termed hCRISPRs. By using available transcriptome datasets, we demonstrate that hCRISPRs are distinctively expressed as small non-coding RNAs (sncRNAs) in cell lines and human tissues. Moreover, expression patterns thereof enabled us to distinguish normal from malignant tissues. In prostate cancer, we confirmed the differential hCRISPR expression between normal adjacent and malignant primary prostate tissue by RT-qPCR and demonstrate that the SHERLOCK and DETECTR dipstick tools are suitable to detect these sncRNAs. We anticipate that the discovery of CRISPRs in the human genome can be further exploited for diagnostic purposes in cancer and other medical conditions, which certainly will lead to the development of point-of-care tests based on the differential expression of the hCRISPRs.

Original languageEnglish
Article number338
JournalCommunications Biology
Volume5
Issue number1
DOIs
Publication statusPublished - 8 Apr 2022

Bibliographical note

Funding Information:
C.S. is a graduate student at Erasmus Postgraduate School of Molecular Medicine and is partially supported by I&I Fund (Erasmus Vrienden Fonds). The bioinformatics team of P.J.v.d.S. receives supporting funding from H2020 projects ImmuneAID and Moodstratification for Data analysis infrastructure. Moreover, national funding has been obtained from the ZonMW project Genomes First for genomics infrastructure. The team of R.L. receives supporting funding from H2020 project STAMINA (ID: 883441), the Chiron Foundation and by PPP Allowance made available by Health~Holland, Top Sector Life Sciences & Health, to stimulate public-private partnerships LSH-TKI foundation grant LSHM18006. Prostate RNA-seq data were generated within the framework of the CTMM research program, project NGS‐ProToCol (grant 03 O‐402). We acknowledge Rene Akre for critical reading and editing the manuscript. Finally, we would like to pay our deepest respect to Prof. Johan W. Mouton, who passed away on the 9 July 2019 due to complications caused by prostate cancer ( https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(19)30441-4/fulltext ). Prof. Mouton was supervisor of author and PhD student Chinmoy Saha, thanks to his support, guidance, motivation and scientific advice this work might form the basis to improve prostate cancer diagnostics and prognostics.

Publisher Copyright:
© 2022, The Author(s).

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