title: Exosome-shuttling microRNA-21 promotes cell migration and invasion-targeting PDCD4 in esophageal cancer.
abstract: Recent evidence indicates that exosomes can mediate certain microRNAs (miRNAs) involved in a series of biological functions in tumor occurrence and development. Our previous studies showed that microRNA-21 (miR-21) was abundant in both esophageal cancer cells and their corresponding exosomes. The present study explored the function of exosome-shuttling miR-21 involved in esophageal cancer progression. We found that exosomes could be internalized from the extracellular space to the cytoplasm. The exosome-derived Cy3-labeled miR-21 mimics could be transported into recipient cells in a neutral sphingomyelinase 2 (nSMase2)-dependent manner. miR-21 overexpression from donor cells significantly promoted the migration and invasion of recipient cells by targeting programmed cell death 4 (PDCD4) and activating its downstream c-Jun N-terminal kinase (JNK) signaling pathway after co-cultivation. Our population plasma sample analysis indicated that miR-21 was upregulated significantly in plasma from esophageal cancer patients and showed a significant risk association for esophageal cancer. Our data demonstrated that a close correlation existed between exosome-shuttling miR-21 and esophageal cancer recurrence and distant metastasis. Thus, exosome-shuttling miR-21 may become a potential biomarker for prognosis among esophageal cancer patients.
authors.affiliation: Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, Jiangsu 210009. P.R. China.
authors.forename: Juan
authors.initials: J
authors.lastname: Liao
authors.affiliation: Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, Jiangsu 210009. P.R. China.
authors.forename: Ran
authors.initials: R
authors.lastname: Liu
authors.affiliation: Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, Jiangsu 210009. P.R. China.
authors.forename: Ya-Juan
authors.initials: YJ
authors.lastname: Shi
authors.affiliation: Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, Jiangsu 210009. P.R. China.
authors.forename: Li-Hong
authors.initials: LH
authors.lastname: Yin
authors.affiliation: Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, Jiangsu 210009. P.R. China.
authors.forename: Yue-Pu
authors.initials: YP
authors.lastname: Pu
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D051017:Apoptosis Regulatory Proteins / Q000235:genetics*; D045744:Cell Line, Tumor; D002465:Cell Movement; D018450:Disease Progression; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000473:pathology*; D055354:Exosomes / Q000235:genetics* / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D011379:Prognosis; D016601:RNA-Binding Proteins / Q000235:genetics*; D015398:Signal Transduction
chemical_list: D051017:Apoptosis Regulatory Proteins; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; C114487:PDCD4 protein, human; D016601:RNA-Binding Proteins