title: MicroRNA-21 expression and its pathogenetic significance in cutaneous melanoma.
abstract: Identification of prognostic biomarkers is timely for melanoma as clinicians seek ways to stratify patients for molecular therapy. MicroRNAs are promising as tissue biomarkers because they can be assayed directly from formalin-fixed paraffin-embedded clinical samples. We previously reported that microRNA-21 (miR-21) was strongly expressed in melanoma relative to naevi and now sought to further assess the significance of this by assessing its relationship with its putative target, PTEN. Clinical melanoma samples were analysed by immunohistochemical analysis for PTEN, stem-loop qRT-PCR for miR-21 and PCR for BRAF/NRAS mutation status. Cell lines were investigated for the effect of anti-miR-21 on PTEN. A total of 81 clinical melanocytic tumour samples were investigated, with uniformly high PTEN expression in the nucleus and cytoplasm of naevi and with preferential loss of PTEN expression in the nucleus of melanoma cells. miR-21 expression was inversely associated with nuclear PTEN expression but not with cytoplasmic PTEN expression. An anti-miR-21 preferentially altered nuclear PTEN in melanoma cell lines. The presence of a BRAF or NRAS mutation had no significant effect on miR-21 expression. These data suggest miR-21 may exert an oncogenic effect in melanoma by favouring redistribution of PTEN to the nucleus.
authors.affiliation: aDepartment of Cancer Studies, University of Leicester bEMPATH, University Hospitals of Leicester NHS Trust, Leicester, UK.
authors.forename: Gerald
authors.initials: G
authors.lastname: Saldanha
authors.forename: Linda
authors.initials: L
authors.lastname: Potter
authors.forename: Yee Shin
authors.initials: YS
authors.lastname: Lee
authors.forename: Sophie
authors.initials: S
authors.lastname: Watson
authors.forename: Priya
authors.initials: P
authors.lastname: Shendge
authors.forename: James H
authors.initials: JH
authors.lastname: Pringle
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002467:Cell Nucleus / Q000378:metabolism / Q000473:pathology; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008545:Melanoma / Q000235:genetics* / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D012878:Skin Neoplasms / Q000235:genetics* / Q000473:pathology; D014407:Tumor Cells, Cultured; D055815:Young Adult
chemical_list: C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human