title: Exosomal microRNA miR-1246 induces cell motility and invasion through the regulation of DENND2D in oral squamous cell carcinoma.
abstract: Metastasis is associated with poor prognosis in cancers. Exosomes, which are packed with RNA and proteins and are released in all biological fluids, are emerging as an important mediator of intercellular communication. However, the function of exosomes remains poorly understood in cancer metastasis. Here, we demonstrate that exosomes isolated by size-exclusion chromatography from a highly metastatic human oral cancer cell line, HOC313-LM, induced cell growth through the activation of ERK and AKT as well as promoted cell motility of the poorly metastatic cancer cell line HOC313-P. MicroRNA (miRNA) array analysis identified two oncogenic miRNAs, miR-342-3p and miR-1246, that were highly expressed in exosomes. These miRNAs were transferred to poorly metastatic cells by exosomes, which resulted in increased cell motility and invasive ability. Moreover, miR-1246 increased cell motility by directly targeting DENN/MADD Domain Containing 2D (DENND2D). Taken together, our findings support the metastatic role of exosomes and exosomal miRNAs, which highlights their potential for applications in miRNA-based therapeutics.
authors.affiliation: Department of Molecular Cytogenetics, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Sujata
authors.initials: S
authors.lastname: Sakha
authors.affiliation: Department of Molecular Cytogenetics, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Tomoki
authors.initials: T
authors.lastname: Muramatsu
authors.affiliation: Project for Personalized Cancer Medicine, Genome Center, Japanese Foundation for Cancer Research, Tokyo, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Ueda
authors.affiliation: Department of Molecular Cytogenetics, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.|Bioresource Research Center, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Johji
authors.initials: J
authors.lastname: Inazawa
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000473:pathology*; D055354:Exosomes / Q000378:metabolism*; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics*; D006801:Humans; D035683:MicroRNAs / Q000502:physiology*; D009062:Mouth Neoplasms / Q000473:pathology*; D009361:Neoplasm Invasiveness / Q000503:physiopathology*; D009362:Neoplasm Metastasis / Q000503:physiopathology*; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: C582173:DENND2D protein, human; D020662:Guanine Nucleotide Exchange Factors; C577700:MIRN1246 microRNA, human; D035683:MicroRNAs; D025521:Tumor Suppressor Proteins