title: miR-193b/365a cluster controls progression of epidermal squamous cell carcinoma.
abstract: Incidence of cutaneous squamous cell carcinomas (cSCCs) constantly increases in the Caucasian population. Developing preferentially on precancerous lesions such as actinic keratoses due to chronic sunlight exposure, cSCCs result from the malignant transformation of keratinocytes. Although a resection of the primary tumor is usually curative, a subset of aggressive cSCCs shows a high risk of recurrence and metastases. The characterization of the molecular dysfunctions involved in cSCC development should help to identify new relevant targets against these aggressive cSCCs. In that context, we have used small RNA sequencing to identify 100 microRNAs (miRNAs) whose expression was altered during chemically induced mouse skin tumorigenesis. The decreased expression of the miR-193b/365a cluster during tumor progression suggests a tumor suppressor role. Ectopic expression of these miRNAs in tumor cells indeed inhibited their proliferation, clonogenic potential and migration, which were stimulated in normal keratinocytes when these miRNAs were blocked with antisense oligonucleotides. A combination of in silico predictions and transcriptome analyses identified several target genes of interest. We validated KRAS and MAX as direct targets of miR-193b and miR-365a. Repression of these targets using siRNAs mimicked the effects of miR-193b and miR-365a, suggesting that these genes might mediate, at least in part, the tumor-suppressive action of these miRNAs.
authors.affiliation: UMR 7275, Centre National de la Recherche Scientifique, Institut de Pharmacologie Moléculaire et Cellulaire, 660 route des Lucioles, F-06560 Valbonne, France.
authors.forename: Cécile
authors.initials: C
authors.lastname: Gastaldi
authors.forename: Thomas
authors.initials: T
authors.lastname: Bertero
authors.forename: Ning
authors.initials: N
authors.lastname: Xu
authors.forename: Isabelle
authors.initials: I
authors.lastname: Bourget-Ponzio
authors.forename: Kévin
authors.initials: K
authors.lastname: Lebrigand
authors.forename: Sandra
authors.initials: S
authors.lastname: Fourre
authors.forename: Alexandra
authors.initials: A
authors.lastname: Popa
authors.forename: Nathalie
authors.initials: N
authors.lastname: Cardot-Leccia
authors.forename: Guerrino
authors.initials: G
authors.lastname: Meneguzzi
authors.forename: Enikö
authors.initials: E
authors.lastname: Sonkoly
authors.forename: Andor
authors.initials: A
authors.lastname: Pivarcsi
authors.forename: Bernard
authors.initials: B
authors.lastname: Mari
authors.forename: Pascal
authors.initials: P
authors.lastname: Barbry
authors.forename: Gilles
authors.initials: G
authors.lastname: Ponzio
authors.forename: Roger
authors.initials: R
authors.lastname: Rezzonico
mesh_terms: D000818:Animals; D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D011905:Genes, ras; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism / Q000473:pathology; D051379:Mice; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D005810:Multigene Family; D009367:Neoplasm Staging; D012878:Skin Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
chemical_list: D050976:Basic-Leucine Zipper Transcription Factors; C546818:MIRN193 microRNA, human; C568257:MIRN193 microRNA, mouse; C546819:MIRN365 microRNA, human; C000589043:MIRN365 microRNA, mouse; D035683:MicroRNAs; C067850:Myc associated factor X