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Insulin-like growth factor-binding protein-7 (IGFBP7) transcript: A-to-I editing events in normal and cancerous human keratinocytes

Archives of Dermatological Research volume 305, pages 519–528 (2013)Cite this article

Abstract

Non-melanoma skin cancers (NMSC) are the most common malignancies in caucasians worldwide. Insulin-like growth factor-binding protein-7 (IGFBP7) was suggested to function as a tumor suppressor gene in several cancers, and to play a role in the proliferation of keratinocytes. A-to-I RNA editing is a post-transcriptional mechanism frequently used to expand and diversify transcriptome and proteome repertoire in eukaryotic cells. A-to-I RNA editing can alter codons, substitute amino acids and affect protein sequence, structure, and function. Two editing sites were identified within the IGFBP7 transcript. To evaluate the expression and editing of IGFBP7 mRNA in NMSC compared to normal epidermis. We examined the expression and mRNA editing level of IGFBP7 in 22 basal cell carcinoma (BCC), 15 squamous cell carcinoma (SCC), and 18 normal epidermis samples that were surgically removed from patients by the Mohs Micrographic Surgery procedure. We studied the effect of IGFBP7 editing on an immortalized HaCaT keratinocyte cell model. IGFBP7 mRNA is over expressed in BCC and SCC compared to normal epidermis. Moreover, the IGFBP7 transcript is highly edited in normal epidermis, but its editing is significantly reduced in BCC and SCC. The edited form of IGFBP7 can inhibit proliferation and induce senescence in cultured keratinocytes. This study describes for the first time A-to-I editing in the coding sequence of a tumor suppressor gene in humans, and suggests that IGFBP7 editing serves as a fine-tuning mechanism to maintain the equilibrium between proliferation and senescence in normal skin.

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Acknowledgments

The authors wish to acknowledge Prof. Gidi Rechavi for his suggestions and for reviewing the manuscript and Dr. Inna Verbovetski-Reiner for her help in apoptosis measurement.

Conflict of interest

The authors declare that they have no conflict of interest.

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Affiliations

  1. Department of Dermatology, Hadassah-Hebrew University Medical Center, P.O.Box 12000, 91010, Jerusalem, Israel

    Malka Hochberg, Leon Gilead, Claes David Enk & Arieh Ingber

  2. Department of Functional Genomics, Sheba Medical Center, Ramat-Gan, Israel

    Yulia Feiler

  3. Ella Institute of Melanoma, Sheba Medical Center, Ramat-Gan, Israel and Tel-Aviv University, Tel-Aviv, Israel

    Gal Markel & Yael Nemlich

  4. Department of Biochemistry and Molecular Biology, IMRIC, Hebrew University-Hadassah Medical School, Jerusalem, Israel

    Polina Denichenko & Rotem Karni

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  1. Malka Hochberg
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  2. Leon Gilead
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Correspondence to Malka Hochberg.

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Hochberg, M., Gilead, L., Markel, G. et al. Insulin-like growth factor-binding protein-7 (IGFBP7) transcript: A-to-I editing events in normal and cancerous human keratinocytes. Arch Dermatol Res 305, 519–528 (2013). https://doi.org/10.1007/s00403-013-1338-5

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  • DOI: https://doi.org/10.1007/s00403-013-1338-5

Keywords

  • IGFBP7
  • RNA-editing
  • BCC and SCC
  • Proliferation
  • Senescence