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Mapping genetic variability in mature miRNAs and miRNA binding sites in prostate cancer

Journal of Human Genetics volume 66, pages 1127–1137 (2021)Cite this article

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Abstract

MicroRNAs (miRNAs) regulate diverse cancer hallmarks through sequence-specific regulation of gene expression, so genetic variability in their seed sequences or target sites could be responsible for cancer initiation or progression. While several efforts have been made to predict the locations of single nucleotide variants (SNVs) at miRNA target sites and associate them with cancer risk and susceptibility, there have been few direct assessments of SNVs in both mature miRNAs and their target sites to assess their impact on miRNA function in cancers. Using genome-wide target capture of miRNAs and miRNA-binding sites followed by deep sequencing in prostate cancer cell lines, here we identified prostate cancer-specific SNVs in mature miRNAs and their target binding sites. SNV rs9860655 in the mature sequence of miR-570 was not present in benign prostate hyperplasia (BPH) tissue or cell lines but was detectable in clinical prostate cancer tissue samples and adjacent normal tissue. SLC45A3 (prostein), a putative oncogene target of miR-1178, was highly upregulated in PC3 cells harboring an miR-1178 seed sequence SNV. Finally, systematic assessment of losses and gains of miRNA targets through 3′UTR SNVs revealed SNV-associated changes in target oncogene and tumor suppressor gene expression that might be associated with prostate carcinogenesis. Further work is required to systematically assess the functional effects of miRNA SNVs.

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Funding

This work was supported by National Institutes of Health grant NCI 5P30CA030199, Florida Department of Health, Bankhead-Coley Cancer Research Program 5BC08 and International Prostate Cancer Foundation (IPCF) to RJP.

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Authors and Affiliations

  1. Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, School of Medicine, Johns Hopkins University, Baltimore, MD, USA

    Bongyong Lee & Ranjan J. Perera

  2. Johns Hopkins All Children’s Hospital, St. Petersburg, FL, USA

    Bongyong Lee, John Marchica & Ranjan J. Perera

  3. Integrative Bioinformatics, National Institute of Environmental Health Sciences, Durham, NC, USA

    Jian-Liang Li

  4. Department Medicine, Stanford University, Palo Alto, CA, USA

    Mark Mercola

  5. AdventHealth 410 Celebration Pl Suite 200, Kissimmee, FL, USA

    Vipul Patel

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Correspondence to Ranjan J. Perera.

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Lee, B., Li, JL., Marchica, J. et al. Mapping genetic variability in mature miRNAs and miRNA binding sites in prostate cancer. J Hum Genet 66, 1127–1137 (2021). https://doi.org/10.1038/s10038-021-00934-w

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