title: Lipid-based nanoparticle delivery of Pre-miR-107 inhibits the tumorigenicity of head and neck squamous cell carcinoma.
abstract: Head and neck squamous cell carcinoma (HNSCC) is the sixth most prevalent cancer worldwide with about 600,000 new cases diagnosed in the last year. Our laboratory showed that miR-107 expression is reduced and functions as a tumor suppressor gene in HNSCC suggesting the potential application of miR-107 as a novel anticancer therapeutic. In this study, we determined the efficiency and efficacy of cationic lipid nanoparticles to deliver pre-miR-107 (NP/pre-miR-107) in HNSCC cells in vitro and in vivo. NP/pre-miR-107 increased delivery of miR-107 into HNSCC cells by greater than 80,000-fold compared to free pre-miR-107. Levels of known miR-107 targets, protein kinase Cε (PKCε), cyclin-dependent kinase 6 (CDK6), and hypoxia-inducible factor 1-β (HIF1-β), decreased following NP/pre-miR-107 treatment. Clonogenic survival, cell invasion, and cell migration of HNSCC cells was inhibited with NP/pre-miR-107. Moreover, NP/pre-miR-107 reduced the cancer-initiating cell (CIC) population and dampened the expression of the core embryonic stem cell transcription factors, Nanog, Oct3/4, and Sox2. In a preclinical mouse model of HNSCC, systemic administration of NP/pre-miR-107 significantly retarded tumor growth by 45.2% compared to NP/pre-miR-control (P < 0.005, n = 7). Kaplan-Meier analysis showed a survival advantage for the NP/pre-miR-107 treatment group (P = 0.017). Our results demonstrate that cationic lipid nanoparticles are an effective carrier approach to deliver therapeutic miRs to HNSCC.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, The Ohio State University Medical Center, Columbus, Ohio 43210, USA.
authors.forename: Longzhu
authors.initials: L
authors.lastname: Piao
authors.forename: Manchao
authors.initials: M
authors.lastname: Zhang
authors.forename: Jharna
authors.initials: J
authors.lastname: Datta
authors.forename: Xiujie
authors.initials: X
authors.lastname: Xie
authors.forename: Tizhi
authors.initials: T
authors.lastname: Su
authors.forename: Hong
authors.initials: H
authors.lastname: Li
authors.forename: Theodoros N
authors.initials: TN
authors.lastname: Teknos
authors.forename: Quintin
authors.initials: Q
authors.lastname: Pan
mesh_terms: D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000628:therapy*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D002470:Cell Survival / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D018014:Gene Transfer Techniques; D006258:Head and Neck Neoplasms / Q000235:genetics / Q000628:therapy*; D006801:Humans; D008055:Lipids / Q000737:chemistry; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000008:administration & dosage* / Q000737:chemistry; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D000077195:Squamous Cell Carcinoma of Head and Neck; D023041:Xenograft Model Antitumor Assays
chemical_list: D008055:Lipids; C549045:MIRN107 microRNA, human; D035683:MicroRNAs