Exosomes secreted from human colorectal cancer cell lines contain mRNAs,             microRNAs and natural antisense RNAs, that can transfer into the human hepatoma             HepG2 and lung cancer A549 cell lines.
Exosomes are microvesicles that are released from various cells into the             extracellular space. It has been reported that the components within exosomes             vary according to the type of secreted cell. In the present study, we investigated             the tetraspanin family proteins CD63, CD9 and CD81 as useful collection markers             of exosomes derived from the three colorectal cancer (CRC) cell lines HCT-15,             SW480 and WiDr. In addition, we aimed to detect the mRNAs, microRNAs and natural             antisense RNAs within the exosomes secreted from the three CRC cell lines. Furthermore,             we examined whether exosomes containing their RNAs were transferred into the hepatoma             cell line HepG2 and lung cancer cell line A549. CD81 was detected in exosomes             secreted from the three CRC cell lines. This result indicates that CD81 can be             a collection marker of exosomes derived from the three CRC cell lines. When the             RNA species within exosomes derived from the three CRC cell lines were examined,             the mRNAs of housekeeping genes such as ACTB and GAPDH, the microRNAs such as             miR-21, miR-192 and miR-221, and the natural antisense RNAs of LRRC24, MDM2 and             CDKN1A genes, were detected. We discovered their natural antisense RNAs within             exosomes for the first time in the present study. Furthermore, PKH67-labeled exosomes             derived from the CRC cell lines were taken up into HepG2 and A549 cells. These             findings indicate that the intracellular RNAs enclosed within exosomes are secreted             to the outside, and exosomes derived from the CRC cell lines are transferred into             HepG2 and A549 cells. In conclusion, we reveal that exosomes derived from the             CRC cell lines contain mRNAs, microRNAs and natural antisense RNAs, and can be             delivered into HepG2 and A549 cells. These findings indicate that exosomal RNAs             can shuttle between cells, and may be involved in the regulation of gene expression             in recipient cells.
Department of Biomedical Sciences, Division of Medical Life Sciences, Hirosaki University School of Health Sciences, Hirosaki, Aomori 036-8564, Japan. mchiba32@cc.hirosaki-u.ac.jp
Mitsuru
M
Chiba
Misako
M
Kimura
Saya
S
Asari
D014408:Biomarkers, Tumor / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics; D055354:Exosomes / Q000235:genetics* / Q000378:metabolism; D018014:Gene Transfer Techniques; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism; D035683:MicroRNAs / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics; D016372:RNA, Antisense / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis* / Q000235:genetics; D060225:Tetraspanin 28 / Q000032:analysis; D060245:Tetraspanin 29 / Q000032:analysis; D060149:Tetraspanin 30 / Q000032:analysis
D014408:Biomarkers, Tumor; D050759:Cyclin-Dependent Kinase Inhibitor p21; D035683:MicroRNAs; D051736:Proto-Oncogene Proteins c-mdm2; D016372:RNA, Antisense; D012333:RNA, Messenger; D060225:Tetraspanin 28; D060245:Tetraspanin 29; D060149:Tetraspanin 30; C493956:CDKN1A protein, human; C546783:MIRN192 microRNA, human; C524940:MIRN21 microRNA, human; C525709:MIR221, human; C497206:MDM2 protein, human