title: MVP-mediated exosomal sorting of miR-193a promotes colon cancer progression.
abstract: Exosomes are emerging mediators of intercellular communication; whether the release of exosomes has an effect on the exosome donor cells in addition to the recipient cells has not been investigated to any extent. Here, we examine different exosomal miRNA expression profiles in primary mouse colon tumour, liver metastasis of colon cancer and naive colon tissues. In more advanced disease, higher levels of tumour suppressor miRNAs are encapsulated in the exosomes. miR-193a interacts with major vault protein (MVP). Knockout of MVP leads to miR-193a accumulation in the exosomal donor cells instead of exosomes, inhibiting tumour progression. Furthermore, miR-193a causes cell cycle G1 arrest and cell proliferation repression through targeting of Caprin1, which upregulates Ccnd2 and c-Myc. Human colon cancer patients with more advanced disease show higher levels of circulating exosomal miR-193a. In summary, our data demonstrate that MVP-mediated selective sorting of tumour suppressor miRNA into exosomes promotes tumour progression.
authors.affiliation: James Graham Brown Cancer Center, University of Louisville, Louisville, Kentucky 40202, USA.
authors.forename: Yun
authors.initials: Y
authors.lastname: Teng
authors.affiliation: Department of Breast and Thyroid Surgery, Huai'an First People's Hospital, Huai'an, Jiangsu 223001, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Ren
authors.affiliation: Program in Biostatistics, Bioinformatics and Systems Biology, The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, Texas 77030, USA.|Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Xin
authors.initials: X
authors.lastname: Hu
authors.affiliation: James Graham Brown Cancer Center, University of Louisville, Louisville, Kentucky 40202, USA.
authors.forename: Jingyao
authors.initials: J
authors.lastname: Mu
authors.affiliation: James Graham Brown Cancer Center, University of Louisville, Louisville, Kentucky 40202, USA.
authors.forename: Abhilash
authors.initials: A
authors.lastname: Samykutty
authors.affiliation: James Graham Brown Cancer Center, University of Louisville, Louisville, Kentucky 40202, USA.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Zhuang
authors.affiliation: James Graham Brown Cancer Center, University of Louisville, Louisville, Kentucky 40202, USA.
authors.forename: Zhongbin
authors.initials: Z
authors.lastname: Deng
authors.affiliation: James Graham Brown Cancer Center, University of Louisville, Louisville, Kentucky 40202, USA.
authors.forename: Anil
authors.initials: A
authors.lastname: Kumar
authors.affiliation: James Graham Brown Cancer Center, University of Louisville, Louisville, Kentucky 40202, USA.
authors.forename: Lifeng
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Kidney Disease Program and Clinical Proteomics Center, University of Louisville, Louisville, Kentucky, USA.
authors.forename: Michael L
authors.initials: ML
authors.lastname: Merchant
authors.affiliation: James Graham Brown Cancer Center, University of Louisville, Louisville, Kentucky 40202, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Yan
authors.affiliation: James Graham Brown Cancer Center, University of Louisville, Louisville, Kentucky 40202, USA.
authors.forename: Donald M
authors.initials: DM
authors.lastname: Miller
authors.affiliation: James Graham Brown Cancer Center, University of Louisville, Louisville, Kentucky 40202, USA.|Robley Rex VA Medical Center, Louisville, Kentucky 40206, USA.
authors.forename: Huang-Ge
authors.initials: HG
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001483:Base Sequence; D018797:Cell Cycle Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000097:blood / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D018450:Disease Progression; D055354:Exosomes / Q000378:metabolism*; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology / Q000556:secondary; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D008954:Models, Biological; D009361:Neoplasm Invasiveness; D034443:RNA Transport; D059016:Tumor Microenvironment; D020394:Vault Ribonucleoprotein Particles / Q000378:metabolism*; D000099187:Major Vault Protein
chemical_list: D018797:Cell Cycle Proteins; D035683:MicroRNAs; D020394:Vault Ribonucleoprotein Particles; D000099187:Major Vault Protein; C486562:CAPRIN1 protein, human; C546818:MIRN193 microRNA, human