title: Insulin-like growth factor-binding protein-7 (IGFBP7) transcript: A-to-I editing events in normal and cancerous human keratinocytes.
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.
authors.affiliation: Department of Dermatology, Hadassah-Hebrew University Medical Center, P.O.Box 12000, 91010, Jerusalem, Israel. malka@hadassah.org.il
authors.forename: Malka
authors.initials: M
authors.lastname: Hochberg
authors.forename: Leon
authors.initials: L
authors.lastname: Gilead
authors.forename: Gal
authors.initials: G
authors.lastname: Markel
authors.forename: Yael
authors.initials: Y
authors.lastname: Nemlich
authors.forename: Yulia
authors.initials: Y
authors.lastname: Feiler
authors.forename: Claes David
authors.initials: CD
authors.lastname: Enk
authors.forename: Polina
authors.initials: P
authors.lastname: Denichenko
authors.forename: Rotem
authors.initials: R
authors.lastname: Karni
authors.forename: Arieh
authors.initials: A
authors.lastname: Ingber
mesh_terms: D000243:Adenosine Deaminase / Q000235:genetics / Q000378:metabolism; D002280:Basal Cell Carcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D016922:Cellular Senescence; D006801:Humans; D018969:Insulin-Like Growth Factor Binding Proteins / Q000235:genetics* / Q000378:metabolism; D015603:Keratinocytes / Q000378:metabolism* / Q000473:pathology; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D012878:Skin Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D014158:Transcription, Genetic; D014162:Transfection
chemical_list: D018969:Insulin-Like Growth Factor Binding Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; C102529:insulin-like growth factor binding protein-related protein 1; C567955:ADARB1 protein, human; D000243:Adenosine Deaminase