title: A functional screen identifies specific microRNAs capable of inhibiting human melanoma cell viability.
abstract: Malignant melanoma is an aggressive form of skin cancer with poor prognosis. Despite improvements in awareness and prevention of this disease, its incidence is rapidly increasing. MicroRNAs (miRNAs) are a class of small RNA molecules that regulate cellular processes by repressing messenger RNAs (mRNAs) with partially complementary target sites. Several miRNAs have already been shown to attenuate cancer phenotypes, by limiting proliferation, invasiveness, tumor angiogenesis, and stemness. Here, we employed a genome-scale lentiviral human miRNA expression library to systematically survey which miRNAs are able to decrease A375 melanoma cell viability. We highlight the strongest inhibitors of melanoma cell proliferation, including the miR-15/16, miR-141/200a and miR-96/182 families of miRNAs and miR-203. Ectopic expression of these miRNAs resulted in long-term inhibition of melanoma cell expansion, both in vitro and in vivo. We show specifically miR-16, miR-497, miR-96 and miR-182 are efficient effectors when introduced as synthetic miRNAs in several melanoma cell lines. Our study provides a comprehensive interrogation of miRNAs that interfere with melanoma cell proliferation and viability, and offers a selection of miRNAs that are especially promising candidates for application in melanoma therapy.
authors.affiliation: Hubrecht Institute, University Medical Center Utrecht, Cancer Genomics Center, Utrecht, The Netherlands.
authors.forename: Jos B
authors.initials: JB
authors.lastname: Poell
authors.forename: Rick J
authors.initials: RJ
authors.lastname: van Haastert
authors.forename: Thijs
authors.initials: T
authors.lastname: de Gunst
authors.forename: Iman J
authors.initials: IJ
authors.lastname: Schultz
authors.forename: Willemijn M
authors.initials: WM
authors.lastname: Gommans
authors.forename: Mark
authors.initials: M
authors.lastname: Verheul
authors.forename: Francesco
authors.initials: F
authors.lastname: Cerisoli
authors.forename: Andre A F L
authors.initials: AAFL
authors.lastname: van Puijenbroek
authors.forename: Paula I
authors.initials: PI
authors.lastname: van Noort
authors.forename: Gregoire P
authors.initials: GP
authors.lastname: Prevost
authors.forename: Roel Q J
authors.initials: RQ
authors.lastname: Schaapveld
authors.forename: Edwin
authors.initials: E
authors.lastname: Cuppen
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival / Q000235:genetics; D005260:Female; D023281:Genomics; D006801:Humans; D008545:Melanoma / Q000473:pathology*; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*
chemical_list: D035683:MicroRNAs